Sleep deprivation and brain energy metabolism : in vivo studies in rats and humans

Sleep deprivation leads to increased subsequent sleep length and depth and to deficits in cognitive performance in humans. In animals extreme sleep deprivation is eventually fatal. The cellular and molecular mechanisms causing the symptoms of sleep deprivation are unclear. This thesis was inspired by the hypothesis that during wakefulness brain energy stores would be depleted, and they would be replenished during sleep. The aim of this thesis was to elucidate the energy metabolic processes taking place in the brain during sleep deprivation. Endogenous brain energy metabolite levels were assessed in vivo in rats and in humans in four separate studies (Studies I-IV). In the first part (Study I) the effects of local energy depletion on brain energy metabolism and sleep were studied in rats with the use of in vivo microdialysis combined with high performance liquid chromatography. Energy depletion induced by 2,4-dinitrophenol infusion into the basal forebrain was comparable to the effects of sleep deprivation: both increased extracellular concentrations of adenosine, lactate, and pyruvate, and elevated subsequent sleep. This result supports the hypothesis of a connection between brain energy metabolism and sleep. The second part involved healthy human subjects (Studies II-IV). Study II aimed to assess the feasibility of applying proton magnetic resonance spectroscopy (1H MRS) to study brain lactate levels during cognitive stimulation. Cognitive stimulation induced an increase in lactate levels in the left inferior frontal gyrus, showing that metabolic imaging of neuronal activity related to cognition is possible with 1H MRS. Study III examined the effects of sleep deprivation and aging on the brain lactate response to cognitive stimulation. No physiologic, cognitive stimulation-induced lactate response appeared in the sleep-deprived and in the aging subjects, which can be interpreted as a sign of malfunctioning of brain energy metabolism. This malfunctioning may contribute to the functional impairment of the frontal cortex both during aging and sleep deprivation. Finally (Study IV), 1H MRS major metabolite levels in the occipital cortex were assessed during sleep deprivation and during photic stimulation. N-acetyl-aspartate (NAA/H2O) decreased during sleep deprivation, supporting the hypothesis of sleep deprivation-induced disturbance in brain energy metabolism. Choline containing compounds (Cho/H2O) decreased during sleep deprivation and recovered to alert levels during photic stimulation, pointing towards changes in membrane metabolism, and giving support to earlier observations of altered brain response to stimulation during sleep deprivation. Based on these findings, it can be concluded that sleep deprivation alters brain energy metabolism. However, the effects of sleep deprivation on brain energy metabolism may vary from one brain area to another. Although an effect of sleep deprivation might not in all cases be detectable in the non-stimulated baseline state, a challenge imposed by cognitive or photic stimulation can reveal significant changes. It can be hypothesized that brain energy metabolism during sleep deprivation is more vulnerable than in the alert state. Changes in brain energy metabolism may participate in the homeostatic regulation of sleep and contribute to the deficits in cognitive performance during sleep deprivation.

Improved termite resistance of wood by wax impregnation.

We investigated the effect of wax-treated and biocide-free wood specimens against three different termite species. A laboratory no-choice test with Reticulitermes banyulensis Clément was carried out in Valencia (Spain) under Mediterranean conditions for eight weeks. Scots pine sapwood (Pinus sylvestris L.) fully impregnated with distinct waxes was used. Two field trials were conducted with Coptotermes acinaciformis (Froggatt) and Mastotermes darwiniensis Froggatt in northern Queensland (Australia) with wax-impregnated beech (Fagus sylvatica L.) for 16 weeks. All three subterranean termites are of major economic importance in their respective regions. The results indicated that feeding pressure by the termites was sufficient within all trials for a valid test. Wax-impregnated Scots pine sapwood was classified as durable. No termites survived the test. The results showed an aging process under submersion conditions, which lead to a classification of moderately durable. The paraffin treatment showed good termite resistance under both test procedures, and was classified as durable. The Australian field trials showed a decreased mass loss of wax-treated beech, in which an amide wax showed excellent termite resistance. The results indicate a clear dependence of the termite resistance on the type and ratio of wax used and the feeding preferences of the specific termite species.

Oral Immune Defense against Chronic Hyperplastic Candidosis

Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrients (source of energy, chemotropism). The hypothesis of this work was that body mobilizes both non-specific and specific host defense against invading candidal cells and that these interactions involve resident epithelial cells, rapidly responding non-specific protector neutrophils and mast cells as well as the antigen presenting and responding den-dritic cell lymphocyte plasma cell system. It is supposed that Candida albicans, as a result of dar-winistic pressure, has developed or is utilizing strategies to evade these host defense reactions by e.g. adhering to biomaterial surfaces and biofilms. The aim of the study was to assess the host defense by taking such key molecules of the anti-candidal defense into focus, which are also more or less characteristic for the main cellular players in candida-host cell interactions. As a model for candidal-host interaction, sections of chronic hyperplastic candidosis were used and compared with sections of non-infected leukoplakia and healthy tissue. In this thesis work, neutrophil-derived anti-candidal α-defensin was found in the epithelium, not only diffusely all over in the epithelium, but as a strong α-defensin-rich superficial front probably able to slow down or prevent penetration of candida into the epithelium. Neutrophil represents the main host defence cell in the epithelium, to which it can rapidly transmigrate from the circulation and where it forms organized multicellular units known as microabscesses (study I). Neutrophil chemotactic inter-leukin-8 (IL-8) and its receptor (IL-8R) were studied and were surprisingly also found in the candidal cells, probably helping the candida to keep away from IL-8- and neutrophil-rich danger zones (study IV). Both leukocytes and resident epithelial cells contained TLR2, TLR4 and TLR6 receptors able to recognize candidal structures via utilization of receptors similar to the Toll of the banana fly. It seems that candida can avoid host defence via stimulation of the candida permissive TLR2 instead of the can-dida injurious TLR4 (study V). TLR also provides the danger signal to the immune system without which it will not be activated to specifically respond against candidal antigens. Indeed, diseased sites contained receptor activator of nuclear factor kappa B ligand (RANKL; II study), which is important for the antigen capturing, processing and presenting dendritic cells and for the T lymphocyte activation (study III). Chronic hyperplastic candidosis provides a disease model that is very useful to study local and sys-temic host factors, which under normal circumstances restrain C. albicans to a harmless commensal state, but failure of which in e.g. HIV infection, cancer and aging may lead to chronic infection.

Predictors of disability retirement: From early intentions to retirement

The strong tendency of elderly employees to retire early and the simultaneous aging of the population have been major topics of policy and scientific debate. A key concern has been the financing of future pension schemes and possible labour shortage, especially in social and health services within the public sector. The aging of the population is inevitable, but efforts can be made to prevent or postpone early exit from the labour force, e.g., by identifying and intervening in the factors that contribute to the process of early retirement due to disability. The associations of intentions to retire early, poor mental health and different psychosocial factors with the process of disability retirement are still poorly understood. The purpose of this study was to investigate the associations of intentions to retire early, poor mental health, work and family related psychosocial factors and experiences of earlier life stages with the process of disability retirement. The data were derived from the Helsinki Health Study (HHS, N=8960) and the Health and Social Support Study (HeSSup, N=25 901). The Helsinki Health Study is an ongoing employee cohort study among middle-aged women and men. The Health and Social Support Study is an ongoing longitudinal study of a working-age sample representative of the Finnish population. The analyses were restricted to respondents 40 years of age or older. Age and gender adjusted prevalence and incidence rates were calculated. Associations were studied by using logistic, multinomial and Cox regression. Strong intentions to retire early were common among employees. Poor mental health, unfavourable working conditions and work-to-family conflicts were clearly associated with increased intentions to retire early. Strong intentions to retire early predicted disability retirement. Risk of disability retirement increased in a dose-response manner with increasing number of childhood adversities. Poor mental and somatic health, life dissatisfaction, heavy alcohol consumption, current smoking, obesity and low socioeconomic status were also predictors of disability retirement. The impact of poor mental health and adverse experiences from earlier life stages, work and family related psychosocial factors, e.g., work-family interface, the subjective experience of well-being and health related risk behaviours on the process of disability retirement should be recognised. Preventive measures against disability retirement should be launched before subjective experience of ill health, work disability and strong intentions to retire early emerge.

Behavior Of High-Voltage Machine Insulation System In The Presence Of Thermal And Electrical Stresses

This paper presents the results on a resin-rich machine insulation system subjected to varying stresses such as electrical (2.6 to 13.3 MV/m) and thermal (40 to 155° C) acting together. Accelerated electro-thermal aging experiments subsequently have been performed to understand the insulation degradation The interpretations are based on several measured properties like capacitance, loss tangent, ac resistance, leakage current, and partial discharge quantities. The results indicate that the changes in properties are not significant below a certain temperature for any applied stress, Beyond this temperature large variations are observed even for low electrical stresses. Electrothermal aging studies reveal that the acceleration of the insulation degradation and the ultimate time to failure depends on the relative values of temperature and voltage stresses. At lower temperatures, below critical, material characteristics of the system predominate whereas beyond this temperature, other phenomena come into play causing insulation deterioration. During aging under combined stresses, it appears that the prevailing temperature of the system has a significant role in the insulation degradation and ultimate failure.

Geriatrician interventions on medication prescribing for frail older people in residential aged care facilities

Objective: In Australian residential aged care facilities (RACFs), the use of certain classes of high-risk medication such as antipsychotics, potent analgesics, and sedatives is high. Here, we examined the prescribed medications and subsequent changes recommended by geriatricians during comprehensive geriatric consultations provided to residents of RACFs via videoconference. Design: This is a prospective observational study. Setting: Four RACFs in Queensland, Australia, are included. Participants: A total of 153 residents referred by general practitioners for comprehensive assessment by geriatricians delivered by video-consultation. Results: Residents’ mean (standard deviation, SD) age was 83.0 (8.1) years and 64.1% were female. They had multiple comorbidities (mean 6), high levels of dependency, and were prescribed a mean (SD) of 9.6 (4.2) regular medications. Ninety-one percent of patients were taking five or more medications daily. Of total medications prescribed (n=1,469), geriatricians recommended withdrawal of 9.8% (n=145) and dose alteration of 3.5% (n=51). New medications were initiated in 47.7% (n=73) patients. Of the 10.3% (n=151) medications considered as high risk, 17.2% were stopped and dose altered in 2.6%. Conclusion: There was a moderate prevalence of potentially inappropriate high-risk medications. However, geriatricians made relatively few changes, suggesting either that, on balance, prescription of these medications was appropriate or, because of other factors, there was a reluctance to adjust medications. A structured medication review using an algorithm for withdrawing medications of high disutility might help optimize medications in frail patients. Further research, including a broader survey, is required to understand these dynamics.

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

Turnover intentions of employees with informal eldercare responsibilities: The role of core self-evaluations and supervisor support

As longevity increases, so does the need for care of older relatives by working family members. This research examined the interactive effect of core self-evaluations and supervisor support on turnover intentions in two samples of employees with informal caregiving responsibilities. Data were obtained from 57 employees from Australia (Study 1) and 66 employees from the United States and India (Study 2). Results of Study 1 revealed a resource compensation effect, that is, an inverse relationship between core self-evaluations and turnover intentions when supervisor care support was low. Results of Study 2 extended these findings by demonstrating resource boosting effects. Specifically, there was an inverse relationship between core self-evaluations and subsequent turnover intentions for those with high supervisor work and care support. In addition, employees' satisfaction and emotional exhaustion from their work mediated the inverse relationship between core self-evaluations and subsequent turnover intentions when supervisor work support and care support were high. Overall, these findings highlight the importance of employee- and supervisor-focused intervention strategies in organizations to support informal caregivers.

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

Paraxial schematic eye models for 7- and 14-year-old Chinese children

Purpose.: To develop three-surface paraxial schematic eyes with different ages and sexes based on data for 7- and 14-year-old Chinese children from the Anyang Childhood Eye Study. Methods.: Six sets of paraxial schematic eyes, including 7-year-old eyes, 7-year-old male eyes, 7-year-old female eyes, 14-year-old eyes, 14-year-old male eyes, and 14-year-old female eyes, were developed. Both refraction-dependent and emmetropic eye models were developed, with the former using linear dependence of ocular parameters on refraction. Results.: A total of 2059 grade 1 children (boys 58%) and 1536 grade 8 children (boys 49%) were included, with mean age of 7.1 ± 0.4 and 13.7 ± 0.5 years, respectively. Changes in these schematic eyes with aging are increased anterior chamber depth, decreased lens thickness, increased vitreous chamber depth, increased axial length, and decreased lens equivalent power. Male schematic eyes have deeper anterior chamber depth, longer vitreous chamber depth, longer axial length, and lower lens equivalent power than female schematic eyes. Changes in the schematic eyes with positive increase in refraction are decreased anterior chamber depth, increased lens thickness, decreased vitreous chamber depth, decreased axial length, increased corneal radius of curvature, and increased lens power. In general, the emmetropic schematic eyes have biometric parameters similar to those arising from regression fits for the refraction-dependent schematic eyes. Conclusions.: The paraxial schematic eyes of Chinese children may be useful for myopia research and for facilitating comparison with other children with the same or different racial backgrounds and living in different places.

A flexible hierarchical approach for facial age estimation based on multiple features

Age estimation from facial images is increasingly receiving attention to solve age-based access control, age-adaptive targeted marketing, amongst other applications. Since even humans can be induced in error due to the complex biological processes involved, finding a robust method remains a research challenge today. In this paper, we propose a new framework for the integration of Active Appearance Models (AAM), Local Binary Patterns (LBP), Gabor wavelets (GW) and Local Phase Quantization (LPQ) in order to obtain a highly discriminative feature representation which is able to model shape, appearance, wrinkles and skin spots. In addition, this paper proposes a novel flexible hierarchical age estimation approach consisting of a multi-class Support Vector Machine (SVM) to classify a subject into an age group followed by a Support Vector Regression (SVR) to estimate a specific age. The errors that may happen in the classification step, caused by the hard boundaries between age classes, are compensated in the specific age estimation by a flexible overlapping of the age ranges. The performance of the proposed approach was evaluated on FG-NET Aging and MORPH Album 2 datasets and a mean absolute error (MAE) of 4.50 and 5.86 years was achieved respectively. The robustness of the proposed approach was also evaluated on a merge of both datasets and a MAE of 5.20 years was achieved. Furthermore, we have also compared the age estimation made by humans with the proposed approach and it has shown that the machine outperforms humans. The proposed approach is competitive with current state-of-the-art and it provides an additional robustness to blur, lighting and expression variance brought about by the local phase features.

The current status of heart failure diagnostic biomarkers

Heart failure (HF) affects approximately 23 million individuals worldwide and this number is increasing, due to an aging and growing population. Early detection of HF is crucial in the management of this debilitating disease. Current diagnostic methods for HF rely heavily on clinical imaging techniques and blood analysis, which makes them less than ideal for population-based screening purposes. Studies focusing on developing novel biomarkers for HF have utilized various techniques and biological fluids, including urine and saliva. Promising results from these studies imply that these body fluids can be used in evaluating the clinical manifestation of HF and will one day be integrated into a clinical workflow and facilitate HF management.

The moderating effects of job control and selection, optimization, and compensation strategies on the age-work ability relationship

Work ability describes employees' capability to carry out their work with respect to physical and psychological job demands. This study investigated direct and interactive effects of age, job control, and the use of successful aging strategies called selection, optimization, and compensation (SOC) in predicting work ability. We assessed SOC strategies and job control by using employee self-reports, and we measured employees' work ability using supervisor ratings. Data collected from 173 health-care employees showed that job control was positively associated with work ability. Additionally, we found a three-way interaction effect of age, job control, and use of SOC strategies on work ability. Specifically, the negative relationship between age and work ability was weakest for employees with high job control and high use of SOC strategies. These results suggest that the use of successful aging strategies and enhanced control at work are conducive to maintaining the work ability of aging employees. We discuss theoretical and practical implications regarding the beneficial role of the use of SOC strategies utilized by older employees and enhanced contextual resources at work for aging employees.

A lifespan perspective on emotion regulation, stress, and well-being in the workplace

Researchers in the field of occupational stress and well-being are increasingly interested in the role of emotion regulation in the work context. Emotion regulation has also been widely investigated in the area of lifespan developmental psychology, with findings indicating that the ability to modify one's emotions represents a domain in which age-related growth is possible. In this chapter, we integrate the literatures on aging, emotion regulation, and occupational stress and well-being. To this end, we review key theories and empirical findings in each of these areas, summarize existing research on age, emotion regulation, and stress and well-being at work, and develop a conceptual model on how aging affects emotion regulation and the stress process in work settings to guide future research. According to the model, age will affect: (1) what kinds of affective work events are encountered and how often; (2) the appraisal of and initial emotional response to affective work events (emotion generation), and; (3) the management of emotions and coping with affective work events (emotion regulation). The model has implications for researchers and practitioners who want to understand and facilitate successful emotion regulation and stress reduction in the workplace among different age groups.

Effects of self-reported wisdom on happiness: Not much more than emotional intelligence?

Wisdom and emotional intelligence are increasingly popular topics among happiness scholars. Despite their conceptual overlap, no empirical research has examined their interrelations and incremental predictive validities. The aims of this study were (a) to investigate associations between multidimensional conceptualizations of self-reported wisdom (Ardelt in Res Aging 25(3):275-324, 2003, 2004) and emotional intelligence (Davies et al. in J Pers Soc Psychol 75:989-1015, 1998) and (b) to examine the joint effects of self-reported wisdom and emotional intelligence on dimensions of happiness (life satisfaction as well as positive and negative affect). Data were provided by two samples: 175 university students and 400 online workers. Correlations between a composite wisdom score, a composite emotional intelligence score, and happiness facets were positive and moderate in size. Regression analyses showed that the effects of composite wisdom on life satisfaction and positive affect (but not negative affect) became weaker and non-significant when composite emotional intelligence was controlled. Additional analyses including three dimensions of the self-reported wisdom (cognitive, reflective, and affective wisdom) and four dimensions of emotional intelligence (self- and others-emotions appraisal, use and regulation of emotion) revealed a more differentiated pattern of results. Implications for future research on wisdom and happiness are discussed.