Application of LC-MS-Based Global Metabolomic Profiling Methods to Human Mental Fatigue.

Mental fatigue is characterized by a reduced capacity for work and a loss of capacity to respond to stimulation and is usually accompanied by a feeling of tiredness and drowsiness. Mental fatigue at work is a serious problem and can raise safety concerns especially in the transportation system. It is believed that mental fatigue is a direct or contributing cause of road and air related accidents and incidents. Psychological studies indicate that fatigue results in reduced work efficiency, alertness, and impaired mental performance. However, its underlying biochemical mechanisms are poorly understood. We hypothesized that the human body is an integrated system, and mental fatigue results in changes not only in psychology but also in biochemistry of the human body. These biochemical changes are detectable in metabolites. We employed global metabolomic profiling methods to screen biochemical changes that occur with mental fatigue in air traffic controllers (ATCs) in civil aviation. A total of 45, all male, ATCs (two batches) were recruited as two mental fatigue groups and 23 executive staff acted as a control group for this study. The volunteers' urine samples were collected before and after their work. The samples were analyzed with liquid chromatography/mass spectrometry equipped with a polar, a weak polar, and a nonpolar column, respectively. Three candidate biomarkers were selected on the basis of statistical significance, coefficient of variance, and compared with data of the three groups. The results suggest that urine metabolites may provide a complete new clue from biochemistry to understand, monitor, and manage human mental fatigue.

Air Force Research Laboratory Integrated Omics Research.

Integrated Omics research capabilities within the Air Force Research Laboratory began in 2003 with the initiation of a Defense Technology Objective project aimed to identify biomarkers of toxicity occurring within the warfighter as a preclinical indicator. Current methods for determining toxic exposures are not responsive enough or created available for deployment to prevent serious health effects. Using Integrated Omics (Genomics/Epigenetics, Proteomics, and Metabonomics) for biomarker discovery, we have identified specific molecular markers which, once validated, could be used for real-time or near-real-time monitoring of the human response to uncharacterized exposures. The determination and use of validated biomarker sets, when installed on a fieldable biomonitor system, could allow fast determination of subclinical organ damage in response to chemical exposures. Since initiation of this program, our group has applied Omics technologies for biomarker discovery in a number of toxicology and human performance projects, including jet fuel exposures and cognitive fatigue.

Symptom clusters during the late menopausal transition stage: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aims of this study were to identify groups of women in the late menopausal transition stage who experienced the same cluster of symptoms and to identify indicators that predicted membership in these distinct groups. METHODS: The sample consisted of a subset of Seattle Midlife Women's Health Study participants who were in the late menopausal transition stage and provided self-report data on symptoms experienced between 1990 and 2005. Latent class analysis (LCA) was used to identify groups of women who experienced similar clusters of the following five symptoms: problem concentrating, hot flashes, joint ache, mood changes, and awakening at night. LCA with multivariate logistic regression was used to identify covariates that predicted membership in each group. RESULTS: Four groups of women were identified: (1) low severity for all symptoms except for joint ache, which was moderate (65%); (2) high severity for all symptoms except for hot flashes, which was moderate (13%); (3) high severity for hot flashes, joint ache, and awakening at night (12%); and (4) high severity for problem concentrating and joint ache (10%). A clear delineation between groups based on individual characteristics was not fully elucidated. CONCLUSIONS: This analysis demonstrates that LCA may be useful to identify women who may experience poorer outcomes related to a higher propensity for severe symptoms. Shifting the focus from single symptoms to symptom clusters will aid in the identification of phenotypic profiles, thus facilitating symptom management strategies that can be tailored to meet the needs of individual women.

Mental and physical fatigue-related biochemical alterations.

OBJECTIVE: To confirm fatigue-related biochemical alterations, we measured various parameters just before and after relaxation and fatigue-inducing mental or physical sessions. METHODS: Fifty-four healthy volunteers were randomized to perform relaxation and fatigue-inducing mental and physical sessions for 4 h in a double-blind, three-crossover design. Before and after each session, subjects were asked to rate their subjective sensations of fatigue, and blood, saliva, and urine samples were taken. RESULTS: After the fatigue-inducing mental and physical sessions, subjective scores of fatigue were increased. After the fatigue-inducing mental session, the vanillylmandelic acid level in urine was higher and plasma valine level was lower than after the relaxation session. In contrast, after the fatigue-inducing physical session, serum citric acid, triacylglycerol, free fatty acid, ketone bodies, total carnitine, acylcarnitine, uric acid, creatine kinase, aspartate aminotransferase, lactate dehydrogenase, cortisol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, plasma branched-chain amino acids, transforming growth factor-beta1 and -beta2, white blood cell and neutrophil counts, saliva cortisol and amylase, and urine vanillylmandelic acid levels were higher and serum free carnitine and plasma total amino acids and alanine levels were lower than those after the relaxation session. CONCLUSION: Some mental or physical fatigue-related biochemical changes were determined. Various biochemical alterations reflecting homeostatic perturbation and its responses might be shown. We believe that our results contribute to clarifying the mechanism of fatigue, developing evaluation methods, and establishing a basis for treatment.

Neuroendocrine reactivity and recovery from work with different physical and mental demands.

OBJECTIVES: The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. METHODS: Neuroendocrine reactivity and recovery were studied by measuring the urinary excretion of adrenaline, noradrenaline, and cortisol during and after 3 workdays, 1 consecutive day off, and a baseline day. The assessment was made in 3 groups of Dutch male workers (N=60) who differed in the nature (mental, physical, and combined mental and physical demands) of their work. Multilevel analyses were performed to fit linear mixed-effects models for each hormone. RESULTS: Main or interaction effects with time of day were found between the workers in combined mental and physical work and the 2 other groups of workers for cortisol, adrenaline, and noradrenaline excretion. In addition, the baseline levels of the 3 hormones were higher in the workers with combined mental and physical work when compared with the other 2 groups. The excretion rates during the workdays were higher than those on the day off, but a trend towards mobilizing less activity was found from the 1st to the 3rd workday. Job demands were negatively related to cortisol excretion. Job control and social demands at work did not affect the excretion rates of the hormones. CONCLUSIONS: Unfavorable effects on cortisol and adrenaline reactivity or recovery was found for workers with combined mental and physical demands when compared with workers doing mainly mental or mainly physical work. The results of the present study are in accordance with the cognitive activation theory and the allostatic load model.

[An evaluation of the strain in the work of teachers]. / Otsenka na naprezhenieto pri rabota na uchiteli.

Psychophysiological studies on teachers' work include generally the evaluation of occupational stressors influencing the work load and strain and the assessment of transient and long-term changes in teachers' functional state and health due to these stressors. Results from investigations of some changes in the functional state of the organism of female teachers working in secondary and technical schools of different profiles were presented in this study. The following parameters were applied: subjective feeling of fatigue, heart rate [HR], excretion rates of 11-oxycorticosteroids (11-OCS), adrenaline (A) and noradrenaline (NA) during work. According to the mean HR values during work a moderate cardio-vascular strain was obtained (HR between 80-90 beats) min. Transient HR values over 100 beats/min were registered during periods connected with specific stressful working conditions. The levels of 11-OCS and the catecholamines excretion rates also indicated a moderate job strain. More pronounced changes in 11-OCS, NA and A were found when teaching in the upper classes of the secondary and technical schools. Significant correlations were established between the changes of HR, 11-OCS, NA and A and some individual characteristics of the examined persons, such as: age, length of service, HR at rest and level of neuroticism. Our data reveal the usefulness of the indices and procedures applied for the evaluation of teachers' strain at work.