Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30-50 years. Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS. We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90-94% of ME/CFS cases. From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers. Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.

Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue.

Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

Fatigue correlates with the decrease in parasympathetic sinus modulation induced by a cognitive challenge.

BACKGROUND: It is known that enhancement of sympathetic nerve activity based on a decrease in parasympathetic nerve activity is associated with fatigue induced by mental tasks lasting more than 30 min. However, to measure autonomic nerve function and assess fatigue levels in both clinical and industrial settings, shorter experimental durations and more sensitive measurement methods are needed. The aim of the present study was to establish an improved method for inducing fatigue and evaluating the association between it and autonomic nerve activity. METHODS: Twenty-eight healthy female college students participated in the study. We used a kana pick-out test (KPT) as a brief verbal cognitive task and recorded electrocardiography (ECG) to measure autonomic nerve activity. The experimental design consisted of a 16-min period of ECG: A pre-task resting state with eyes open for 3 min and eyes closed for 3 min, the 4-min KPT, and a post-task resting state with eyes open for 3 min and eyes closed for 3 min. RESULTS: Baseline fatigue sensation, measured by a visual analogue scale before the experiment, was associated with the decrease in parasympathetic sinus modulation, as indicated the by ratio of low-frequency component power (LF) to high-frequency component power (HF), during the KPT. The LF/HF ratio during the post-KPT rest with eyes open tended to be greater than the ratio during the KPT and correlated with fatigue sensation. Fatigue sensation was correlated negatively with log-transformed HF, which is an index of parasympathetic sinus modulation, during the post-KPT rest with eyes open. CONCLUSIONS: The methods described here are useful for assessing the association between fatigue sensation and autonomic nerve activity using a brief cognitive test in healthy females.

Autonomic function is associated with health-related quality of life in patients with end-stage renal disease: a case-control study.

OBJECTIVE: In the present study, we assessed the associations among fatigue, quality of life (QOL), clinical parameters, and body mass index (BMI) with autonomic function in end-stage renal disease (ESRD) patients undergoing hemodialysis as well as fatigue-free healthy subjects. DESIGN AND METHODS: This was a case-control study. This study compared autonomic function in ESRD patients (n = 192) to that of healthy subjects (n = 282) and evaluated its association with fatigue, QOL, and clinical parameters such as glucose, albumin, cholesterol, and BMI. Fatigue was evaluated by a recently established fatigue questionnaire and performance status, and QOL was evaluated with the kidney disease QOL questionnaire. With regards to autonomic function, spontaneous beat-to-beat variations were measured, according to time- (standard deviation of all normal a-wave intervals [CVa-a%]) and frequency domains (low frequency [LF] power, high frequency [HF] power, and LF/HF ratio) with acceleration plethysmography. RESULTS: CVa-a%, LF power, HF power, and LF/HF ratio were significantly lower in ESRD patients than healthy subjects. There were significant inverse correlations between these factors and age in healthy subjects, but not in ESRD patients. Although the fatigue score was not associated with any autonomic parameters, ESRD patients with impaired performance status exhibited a significantly lower LF/HF ratio. Moreover, in ESRD patients, the LF/HF ratio was significantly and positively associated with several components of QOL, including physical functioning and role emotional, independent of other clinical parameters and BMI. CONCLUSIONS: Impaired autonomic function is significantly associated with fatigue and impaired QOL in dialysis patients.

Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study.

BACKGROUND: Fatigue during radiation therapy in women with breast cancer can decrease quality of life (QOL), yet it is often underestimated and needs to be evaluated objectively. This longitudinal study aimed to evaluate fatigue and QOL of women with breast cancer undergoing radiotherapy with a simple autonomic function measurement. METHODS: Women with breast cancer who underwent postoperative radiotherapy in eight cancer care hospitals in Chubu and Kinki regions in Japan were recruited between October 2021 and June 2022. The women underwent a self-administered questionnaire that included the Cancer Fatigue Scale (CFS) and the Short Form-8 Health Survey (SF-8) and an autonomic nervous function measurement using a simple, non-invasive device before (T0, baseline), mid (T1), and at the end (T2) of treatment. RESULTS: The 57 women showed similar trends, with CFS scores and log LF/HF ratio being the highest at T0 and significantly decreasing at T1 (both p < 0.05). The log LF/HF trends differed between those with high and low baseline log LF/HF values. Women with mental component summary (MCS) score improvement (T0 to T2) had the highest log LF/HF ratio at T0 and had significantly lower log LF/HF values at T1 and T2 than at T0 (p < 0.01 and p < 0.05, respectively). The change of (⊿) MCS from T0 to T1 was negatively correlated with ⊿log LF/HF from T0 to T1 (r = - 0.36, p < 0.01). CONCLUSIONS: Measurement of autonomic nerve function with a simple device is useful for objective fatigue assessment during radiotherapy. Psychological support is important as improvement in mental health helps improve autonomic nerve function and, in turn, fatigue.

No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan.

BACKGROUND: The involvement of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer (PC) and chronic fatigue syndrome (CFS) is disputed as its reported prevalence ranges from 0% to 25% in PC cases and from 0% to more than 80% in CFS cases. To evaluate the risk of XMRV infection during blood transfusion in Japan, we screened three populations--healthy donors (n = 500), patients with PC (n = 67), and patients with CFS (n = 100)--for antibodies against XMRV proteins in freshly collected blood samples. We also examined blood samples of viral antibody-positive patients with PC and all (both antibody-positive and antibody-negative) patients with CFS for XMRV DNA. RESULTS: Antibody screening by immunoblot analysis showed that a fraction of the cases (1.6-3.0%) possessed anti-Gag antibodies regardless of their gender or disease condition. Most of these antibodies were highly specific to XMRV Gag capsid protein, but none of the individuals in the three tested populations retained strong antibody responses to multiple XMRV proteins. In the viral antibody-positive PC patients, we occasionally detected XMRV genes in plasma and peripheral blood mononuclear cells but failed to isolate an infectious or full-length XMRV. Further, all CFS patients tested negative for XMRV DNA in peripheral blood mononuclear cells. CONCLUSION: Our data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.

Mental fatigue caused by prolonged cognitive load associated with sympathetic hyperactivity.

BACKGROUND: It is known that chronic fatigue is associated with sympathetic hyperactivity. However, the relationship between autonomic function and mental fatigue caused by a prolonged mental load in healthy humans is still unclear. Thus, in order to clarify the mechanisms underlying mental fatigue, we examined the association between mental fatigue and autonomic functions. METHODS: The study group comprised 10 healthy participants. To induce mental fatigue, participants performed mental tasks, which consisted of the advanced trail making test, kana pick-out test and mirror drawing test, for 8 hr, corresponding to a normal work day. Autonomic functions were measured by accelerated plethysmography before and after the fatigue-inducing mental tasks. As a control, the same participants completed an 8-hr relaxation session 4 weeks before the fatigue session. RESULTS: After the 8-hr relaxation session, low-frequency component power (LF), high-frequency component power (HF) and low-frequency component power/high-frequency component power ratio (LF/HF ratio) were not changed from baseline. In contrast, after the fatigue session, the HF and LF/HF ratio were significantly changed from baseline; specifically, the HF was lower and LF/HF ratio was higher as compared to those after the relaxation session. CONCLUSIONS: Sympathetic hyperactivity based on decreased parasympathetic activity is associated with mental fatigue induced by prolonged cognitive load.

Autonomic nervous alterations associated with daily level of fatigue.

BACKGROUND: Fatigue is a common symptom in both sick and healthy people. We examined autonomic nervous alterations associated with fatigue to clarify the mechanisms underlying fatigue. METHODS: The study group consisted of 19 healthy participants who performed a 2-back test for 30 min as a fatigue-inducing mental task session. Before and after the session, they completed the advanced trail making test (ATMT) for 30 min for mental fatigue evaluation, subjective scales to measure fatigue sensation, and underwent electrocardiography to allow assessment of autonomic nerve activities. RESULTS: After the fatigue-inducing task, the total error counts on the ATMT tended to increase (P = 0.076); the ATMT for total trial counts (P = 0.001), the subjective level of fatigue (P < 0.001), and the % low-frequency power (%LF) (P = 0.035) increased significantly; and the % high-frequency power (%HF) decreased compared with before the fatigue-inducing task although this did not reach the statistical significance (P = 0.170). Although LF measured in absolute units did not change significantly before and after the fatigue-inducing task (P = 0.771), and HF measured in absolute units decreased after the task (P = 0.020). The %LF and LF/HF ratio were positively associated with the daily level of fatigue evaluated using Chalder's fatigue scale. In addition, %HF was negatively associated with the fatigue score. CONCLUSIONS: Increased sympathetic activity and decreased parasympathetic activity may be characteristic features of both acute and daily levels of fatigue. Our findings provide new perspectives on the mechanisms underlying fatigue.

Increase in rear-end collision risk by acute stress-induced fatigue in on-road truck driving.

Increasing road crashes related to occupational drivers' deteriorating health has become a social problem. To prevent road crashes, warnings and predictions of increased crash risk based on drivers' conditions are important. However, in on-road driving, the relationship between drivers' physiological condition and crash risk remains unclear due to difficulties in the simultaneous measurement of both. This study aimed to elucidate the relationship between drivers' physiological condition assessed by autonomic nerve function (ANF) and an indicator of rear-end collision risk in on-road driving. Data from 20 male truck drivers (mean ± SD, 49.0±8.2 years; range, 35-63 years) were analyzed. Over a period of approximately three months, drivers' working behavior data, such as automotive sensor data, and their ANF data were collected during their working shift. Using the gradient boosting decision tree method, a rear-end collision risk index was developed based on the working behavior data, which enabled continuous risk quantification. Using the developed risk index and drivers' ANF data, effects of their physiological condition on risk were analyzed employing a logistic quantile regression method, which provides wider information on the effects of the explanatory variables, after hierarchical model selection. Our results revealed that in on-road driving, activation of sympathetic nerve activity and inhibition of parasympathetic nerve activity increased each quantile of the rear-end collision risk index. The findings suggest that acute stress-induced drivers' fatigue increases rear-end collision risk. Hence, in on-road driving, drivers' physiological condition monitoring and ANF-based stress warning and relief system can contribute to promoting the prevention of rear-end truck collisions.

The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients.

BACKGROUND: Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS) has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased alpha-MSH plasma levels may also occur in CFS patients. We therefore examined alpha-MSH levels in CFS patients. METHODS: Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of alpha-MSH, adrenocorticotropic hormone (ACTH), serum cortisol and dehydroepiandrosterone sulfate (DHEA-S). Mean levels of alpha-MSH were compared between the CFS and control groups using Welch's t test. RESULTS: The mean plasma alpha-MSH concentration in the CFS group (17.9 +/- 1.0 pg/mL) was significantly higher than that in healthy controls (14.5 +/- 1.0 pg/mL, p = 0.02). However, there was a wide range of values in the CFS group. The factors correlated with the plasma alpha-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma alpha-MSH values (p = 0.04, rs = -0.28), but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively). The CFS patients were divided into two groups: patients diagnosed for

Premorbid personality in chronic fatigue syndrome as determined by the Temperament and Character Inventory.

BACKGROUND: Using the Temperament and Character Inventory (TCI), we examined personality characteristics in patients with chronic fatigue syndrome (CFS) compared with healthy control subjects, and CFS patients with and without psychiatric diseases. There have been no previous reports assessing personality in CFS patients using the TCI. METHODS: A total of 211 CFS patients and 90 control subjects completed the TCI and the Chalder Fatigue Scale questionnaires. RESULTS: Compared with control subjects, CFS patients demonstrated significantly lower premorbid Novelty Seeking, and higher Harm Avoidance and persistence. The fatigue score for CFS patients with psychiatric diseases was higher than that for CFS patients without psychiatric diseases. Patients with CFS with psychiatric diseases showed lower premorbid Self-Directedness when compared with CFS patients without psychiatric diseases. The fatigue score was negatively correlated with premorbid Self-Directedness and Cooperativeness, and positively correlated with Harm Avoidance among CFS patients. CONCLUSION: This study supported the stereotyped image of CFS patients as perfectionists, which is similar to the Persistence score, and neurotics, which is similar to the Harm Avoidance score. Patients displaying greater neuroticisms and poorer social and communication skills, similar to the Self-Directedness and Cooperativeness scores, tend to have intercurrent psychiatry diseases and show more severe symptoms of CFS.

Relationship between truck driver fatigue and rear-end collision risk.

The fatigue of truck, bus, and taxi drivers has been a causal trigger for road accidents. However, the relationship between collision risk and the extent of objective fatigue has yet to be confirmed. In this study, we aimed to identify the relationship between autonomic nerve function as an objective parameter of fatigue and the extent of rear-end collision risk, which includes not only objectively risky events but also situations in which truck drivers require safety guidance from safety transport managers. Data of 33 truck driver participants (2 females, 31 males, 46.0 ± 9.1 years old, min-max: 24-65 years old) were analyzed. Drive recorder and automotive sensor data were collected over an eight-month period, and the autonomic nerve function during resting state in drivers was evaluated daily, pre- and post-shift, using pulse waves and electrocardiographic waveform measurement. The rear-end collision risk Index was developed using decision tree analysis of the audiovisual drive recorder data and distance data from the front automotive sensors. The rear-end collision risk index of shift-day was positively correlated with the sympathetic nerve activity index of post-shift condition on the previous day. This suggests that fatigue-related sympathetic nerve overactivity of post-shift condition increases the rear-end collision risk in the following day. Measures, such as actively seeking rest and undertaking fatigue recovery according to the degree of sympathetic nerve activity of post-shift condition, are necessary in order to prevent truck drivers' rear-end collisions.

Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating disease with no molecular diagnostics and no treatment options. To identify potential markers of this illness, we profiled 48 patients and 52 controls for standard laboratory tests, plasma metabolomics, blood immuno-phenotyping and transcriptomics, and fecal microbiome analysis. Here, we identified a set of 26 potential molecular markers that distinguished ME/CFS patients from healthy controls. Monocyte number, microbiome abundance, and lipoprotein profiles appeared to be the most informative markers. When we correlated these molecular changes to sleep and cognitive measurements of fatigue, we found that lipoprotein and microbiome profiles most closely correlated with sleep disruption while a different set of markers correlated with a cognitive parameter. Sleep, lipoprotein, and microbiome changes occur early during the course of illness suggesting that these markers can be examined in a larger cohort for potential biomarker application. Our study points to a cluster of sleep-related molecular changes as a prominent feature of ME/CFS in our Japanese cohort.

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.

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders.

AIMS: Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two-year prospective follow-up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders. METHODS: A total of 155 patients who met the Japanese case definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow-up interview approximately 24 months later. RESULTS: Of the 70 patients with chronic fatigue syndrome, 33 patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome. CONCLUSIONS: Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is necessary in addition to the medical treatment given for chronic fatigue syndrome.

Stress and coping styles are associated with severe fatigue in medical students.

Fatigue is a common complaint among medical students and researchers consider it to be related to poor academic outcomes. The authors' goal in the present study was to determine whether stress and coping strategies were associated with fatigue in medical students. The study group consisted of 73 second-year healthy students attending the Osaka City University Graduate School of Medicine. Participants completed a questionnaire about fatigue (Japanese version of Chalder Fatigue Scale), stress, stress coping (Japanese version of the Coping Inventory for Stressful Situations), overwork, and nocturnal sleeping hours. On univariate and multivariate logistic regression analyses adjusted for age and gender, stress was positively associated with fatigue. In addition, after adjustment for age, gender, and emotion- and task-oriented stress coping activities, avoidance-oriented stress coping activity was associated with fatigue. The results suggest that stress and the coping style are correlated with fatigue in medical students.

Application of autonomic nervous function evaluation to job stress screening.

The present study focuses on the evaluation of autonomic nervous function, which is increasingly being used as an objective measure of fatigue state. It has recently been reported that autonomic nervous activity, which is expressed as total heart rate variability (HRV) power, is associated with, and can be used as an objective measure of, mental and physical fatigue. Total HRV power (log (LF + HF)) has been shown to decline with ageing, and thus cannot be utilized as a fatigue index in populations with a different age composition. In the present study, we devised standard scores (deviation value) for autonomic nervous activity corrected for individual age calculated from the distribution of such activity in individual age cohorts. This allowed us to accurately evaluate an individual's autonomic nervous activity, even when that individual was part of a group with members of different ages. Standard scores were quantified using autonomic nervous function data gathered from 1,969 healthy individuals (age range 20-77 years). The efficacy of this method in mental health screening was investigated by evaluating both autonomic nervous function and subjective levels of fatigue among corporate workers. Based on results from the Brief Job Stress Questionnaire recommended by the research team of the Ministry of Health, Labour and Welfare, 103 participants were divided into two groups (a high-stress group [n = 17] and a non-high-stress group [n = 86]). Visual analog scale (VAS) scores for all fatigue-related symptoms were significantly higher among the high-stress than among the non-high-stress group (p < 0.01). The mean standard score for autonomic nervous activity was 56.3 for the non-high-stress group. The score for the high-stress group was significantly lower, at 47.9 (p < 0.01), indicating that autonomic nervous function was reduced among participants who experienced high stress. According to an analysis of raw and standard scores in each domain, autonomic nervous activity did not significantly correlate with stress-causing factors (e.g., overwork) or other factors affecting stress responses (e.g., support from supervisors and colleagues), but did exhibit a significant positive correlation with physical and mental responses to stress (r = 0.334, p < 0.01). Lower raw scores for mental and physical responses to stress represent stronger subjective symptoms. Moreover, greater stress responses were found to be associated with lower standard scores for autonomic nervous activity. In terms of fatigue-related symptoms rated using the VAS, autonomic nervous activity negatively correlated with mental stress, physical stress, fatigue/malaise, depressed mood, anxiety/fear, tension, irritation/anger, cognitive decline, and muscle/joint/general pain, and positively correlated with motivation/vitality. Reduced autonomic nervous activity was observed with high stress, confirming that standard scores for autonomic nervous activity are associated with mental and physical responses to stress and subjective fatigue-related symptoms. These results indicate that the evaluation of autonomic nervous activity using standard scores (deviation value) is a useful tool for the objective measurement of fatigue state, even in groups with members of different ages, and can be applied as a useful objective health index to evaluate industrial fatigue.

Tissue factor expression on monocytes induced by anti-phospholipid antibodies as a strong risk factor for thromboembolic complications in SLE patients.

Our aim was to clarify the role of anti-phospholipid antibodies in the pathogenesis of monocyte tissue factor (TF) expression and thromboembolic complications (TE) in patients with SLE. We examined cell surface expression of TF on monocytes in 93 SLE patients. Monocyte TF expression was significantly higher in SLE patients who had TE than in other SLE patients, and confirmed that the high expression of monocyte TF was a strong risk factor for TE. Furthermore, the presence of anti-cardiolipin/beta2-glycoprotein I antibodies (anti-CL/beta2-GPI) was strongly associated with the high expression of monocyte TF. We therefore studied the in vitro effect of IgG anti-CL/beta2-GPI on lipopolysaccharide (LPS)-induced expression of TF on monocytes in healthy peripheral blood and found that purified IgG containing anti-CL/beta2-GPI significantly enhanced LPS-induced monocyte TF expression. These results suggest that anti-CL/beta2-GPI cause persistently high TF expression on monocyte, which may contribute to the risk of thromboembolic events in SLE patients.

Antifatigue effects of coenzyme Q10 during physical fatigue.

OBJECTIVE: This study examined the effects of coenzyme Q10 administration on physical fatigue. METHODS: In a double-blinded, placebo-controlled, three crossover design, 17 healthy volunteers were randomized to oral coenzyme Q10 (100 or 300 mg/d) or placebo administration for 8 d. As a fatigue-inducing physical task, subjects performed workload trials on a bicycle ergometer at fixed workloads twice for 2 h and then rested for 4 h. During the physical tasks, subjects performed non-workload trials with maximum velocity for 10 s at 30 min (30-min trial) after the start of physical tasks and 30 min before the end of the tasks (210-min trial). RESULTS: The change in maximum velocity from the 30- to the 210-min trial in the 300-mg coenzyme Q10-administered group was higher than that in the placebo group. In addition, subjective fatigue sensation measured on a visual analog scale in the 300-mg coenzyme Q10-administered group after the fatigue-inducing physical task and recovery period was alleviated when compared with that in the placebo group. CONCLUSION: Oral administration of coenzyme Q10 improved subjective fatigue sensation and physical performance during fatigue-inducing workload trials and might prevent unfavorable conditions as a result of physical fatigue.