Effects of green tea and roasted green tea on human responses.

Our objective was to elucidate the effects of tea consumption on refreshment and stress reduction/recovery through examining the multiple associations among factors such as various physiological responses and task performance. Participants included 20 healthy young men who performed a mental arithmetic task while 11 physiological responses were measured. The experiments were conducted twice under different beverage consumption conditions on separate days. The mental arithmetic task was executed six times in 1 day; participants ingested hot water, green tea, or roasted green tea (hojicha) before each task. Several subjective assessments: subjective fatigue, stress, mental workload, and flow were evaluated after each task. The R-R intervals, heart rate variability spectral components, the Poincaré plot indices (SD1 and SD2) and plethysmogram amplitude tended to decrease during task periods compared to resting periods. Tissue blood volume/flow (TBV, TBF) and near-infrared spectroscopy responses (NIRS) were lower in the tea condition than in the hot water condition. By scrutinizing various indicators, we found that aromatic stimulation of Japanese tea beverages has the potential to induce positive effects, enhance mental task performance, promote refreshment, and alleviate feelings of fatigue. These positive effects were observed even in small quantities and within a short duration, mirroring responses observed in daily consumption.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions.

INTRODUCTION: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the "neoplastic, benign neoplasm, and low-grade carcinoma" category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. METHODS: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. RESULTS: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into "negative" or "atypical" by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as "suspicious" or "malignant" by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. CONCLUSIONS: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice.

[Mental Workload Assessment of Health Care Staff by NASA-TLX].

The National Aeronautics Space Administration Task Load Index (NASA-TLX) is the most frequently used mental workload assessment method. This article reviews 26 papers which report mental workload evaluation in health care staff, categorizing them into laparoscopic surgery, anesthesia, ICU, electronic record, patient controlled analgesia, emergency, display and others. Although indices other than NASA-TLX were also used in these papers, this review describes the results of NASA-TLX only.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens.

INTRODUCTION: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) "negative for malignancy," (2) "atypical cells," (3) "suspicious for malignancy," and (4) "malignancy." OBJECTIVE: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples. METHODS: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems. RESULTS: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for "negative for malignancy," 45.6% for "atypical cells," 74.7% for "suspicious for malignancy," and 88.1% for "malignancy." CONCLUSIONS: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.

Cytological differences between invasive and noninvasive or minimally invasive lung adenocarcinomas diagnosed in Japanese patients using needle biopsy specimens of pulmonary lesions ≤3 cm in diameter.

BACKGROUND: According to the WHO classification for lung cancer, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have a better prognosis than invasive adenocarcinoma (IAD). However, detecting the foci of invasion in lung adenocarcinomas radiologically remains difficult. The present study examined whether or not differences in the cytological characteristics between IAD and AIS or MIA (noninvasive or minimally invasive adenocarcinomas [NMIAD]) plays a role in the differential diagnosis. METHODS: Seventy surgical resection specimens of primary lung adenocarcinoma with preoperative cytology, in which several parameters were evaluated and assessed. RESULTS: The histopathological diagnoses of surgical resection specimens were AIS in 8, MIA in 31, IAD in 31 including lepidic adenocarcinoma in 9, and papillary adenocarcinoma in 22. NMIAD had a 100% 5-year recurrence-free survival (RFS), while IAD had an 82.8% 5-year RFS. The numbers of tumor cells (at ×10 magnification in 10 fields) were 60.3 ± 40.5 in IAD and 39.8 ± 28.7 in NMIAD (P = 0.0017). A univariate analysis of cytological parameters revealed significant differences in large tumor cell clusters, three-dimensional (3D) tumor cell clusters, and irregular nuclear contours between the two groups. The frequency of irregular nuclear contours continued to be significantly different according to a multivariate analysis. CONCLUSION: Large or 3D tumor cell clusters and irregular nuclear contours may be important cytological factors for distinguishing IAD from NMIAD, with the latter being potentially more important for distinguishing between the two groups.

Association between Breast Cancer Recurrence and Cellular Dissociation Assessed Using Fine-Needle Aspiration.

OBJECTIVE: To determine the associations between breast cancer recurrence and cytological findings of fine-needle aspiration cytology (FNAC). STUDY DESIGN: The study included 117 women who had undergone a modified radical mastectomy for invasive ductal carcinoma of the breast. FNAC samples of these patients were reexamined, and cytological findings, such as cellular dissociation, nuclear pleomorphism, nuclear atypia, chromatin pattern, and nuclear size, were scored. Uni- and multivariate analyses were performed to determine the prognostic significance of the cytological findings. Corresponding cancer tissues were immunostained for estrogen receptor, progesterone receptor, human epidermal growth factor 2 (HER2), p53, and E-cadherin to determine their associations with cytological findings. Coexpression of Arp2 and WAVE2 was also examined immunohistochemically as a cell locomotion signal. RESULTS: Cellular dissociation (p = 0.0259) and nuclear size (p = 0.0417) were significantly associated with cancer recurrence. Multivariate analysis showed that cellular dissociation and histological grade were significant independent predictors of cancer recurrence. Cellular dissociation was found to be associated with coexpression of Arp2 and WAVE2 (p = 0.0356) and HER2 (p = 0.0469). CONCLUSION: The cytological finding of cell dissociation was associated with the activation of Arp2 and WAVE2 signals and was an independent predictor of recurrence.

Assessment of operators' mental workload using physiological and subjective measures in cement, city traffic and power plant control centers.

BACKGROUND: The present study aimed to evaluate the operators' mental workload (MW) of cement, city traffic control and power plant control centers using subjective and objective measures during system vital parameters monitoring. METHODS: This cross-sectional study was conducted from June 2014 to February 2015 at the cement, city traffic control and power plant control centers. Electrocardiography and electroencephalography data were recorded from forty males during performing their daily working in resting, low mental workload (LMW), high mental workload (HMW) and recovery conditions (each block 5 minutes). The NASA-Task Load Index (TLX) was used to evaluate the subjective workload of the operators. RESULTS: The results showed that increasing MW had a significant effect on the operators subjective responses in two conditions ([1,53] = 216.303, P < 0.001, η2 = 0.803). Also,the Task-MW interaction effect on operators subjective responses was significant (F [3, 53] = 12.628,P < 0.001, η2 = 0.417). Analysis of repeated measures analysis of variance (ANOVA) indicated that increasing mental demands had a significant effect on heart rate, low frequency/high frequency ratio, theta and alpha band activity. CONCLUSION: The results suggested that when operators' mental demands especially in traffic control and power plant tasks increased, their mental fatigue and stress level increased and their mental health deteriorated. Therefore, it may be necessary to implement an ergonomic program or administrative control to manage mental probably health in these control centers. Furthermore, by evaluating MW, the control center director can organize the human resources for each MW condition to sustain the appropriate performance as well as improve system functions.

Effects of mental workload on physiological and subjective responses during traffic density monitoring: A field study.

This study evaluated operators' mental workload while monitoring traffic density in a city traffic control center. To determine the mental workload, physiological signals (ECG, EMG) were recorded and the NASA-Task Load Index (TLX) was administered for 16 operators. The results showed that the operators experienced a larger mental workload during high traffic density than during low traffic density. The traffic control center stressors caused changes in heart rate variability features and EMG amplitude, although the average workload score was significantly higher in HTD conditions than in LTD conditions. The findings indicated that increasing traffic congestion had a significant effect on HR, RMSSD, SDNN, LF/HF ratio, and EMG amplitude. The results suggested that when operators' workload increases, their mental fatigue and stress level increase and their mental health deteriorate. Therefore, it maybe necessary to implement an ergonomic program to manage mental health. Furthermore, by evaluating mental workload, the traffic control center director can organize the center's traffic congestion operators to sustain the appropriate mental workload and improve traffic control management.

Primary large cell neuroendocrine carcinoma of the ureter.

Large cell neuroendocrine carcinoma (LCNEC) is the rarest type of urinary tract malignancy. Herein, we report a case of LCNEC that arose in the ureter of a 78-year-old Japanese man with a history of ascending colon cancer that had been excised by a right hemicolectomy. Left-sided hydronephrosis associated with the ureteral tumor was discovered during follow-up. A left nephroureterectomy combined with a partial resection of the urinary bladder was performed because atypical cells were detected using voided urine cytology. A histopathological examination revealed that the ureteral tumor contained large atypical epithelial cells of neuroendocrine morphology without a urothelial carcinomatous component. The neoplastic cells were immunohistochemically positive for synaptophysin, chromogranin A, CD56, and cytokeratins, but they were negative for uroplakin III and thyroid transcription factor-1. The Ki-67 labeling index of the neoplastic cells was 50%. Transmission electron microscopy demonstrated the presence of numerous dense granules in the cytoplasm of the neoplastic cells. The ureteral lesion was finally classified as stage III, pT3 cN0 cM0. The patient's postoperative course was uneventful without chemoradiotherapy, and LCNEC did not recur in the subsequent nine months. This case demonstrates that LCNEC can occur in the ureter, which normally does not contain neuroendocrine cells in the urothelium.

Regulatory frameworks for cell therapy products in Japan.

This paper reviews regulatory frameworks for cell therapy products in Japan. Two procedures are used to investigate the use of new cell therapy products in Japan. One is to perform clinical trials in accordance with the provisions of the Pharmaceuticals Affairs Act (PAA); the other is to perform clinical research in accordance with the provisions of the Medical Practitioners Act. For full commercialization of medical products in Japan, we must consider the universal health care system. All medical products used to treat patients in the system must be approved, in accordance with the provisions of the PAA, as drugs or medical devices. Thus, researchers in academia who have developed new cell therapy products should consider performing clinical trials in accordance with the provisions of the PAA to test their products clinically. This article describes development and review processes for new drug/device applications in accordance with the provisions of the PAA and gives an example of clinical review of a cell therapy product by the Pharmaceuticals and Medical Devices Agency.

Physiological responses to workload change. A test/retest examination.

The purpose of this study is to examine the test/retest consistency of physiological responses induced by mental tasks. Fifteen healthy male university students were recruited as participants. They were instructed to perform a 5-min Multi-Attribute Task Battery (MATB) trial three times successively. The task difficulty level of the tracking task of the second trial was set as medium (M). The first one was set as more difficult (H) and the last trial was easiest (L). The difficulty levels of the other two tasks (resource management and system monitoring) of the MATB were identical for all three trials. The participants repeated this procedure on three different days separated by at least a 1-day interval. The order of the tasks was the same for all repeated trials, i.e., H-M-L. Tissue blood volume from the tip of the nose using a laser Doppler blood flow meter, skin potential level (SPL), ECG from three leads on the chest, systolic time intervals (pre-ejection period, left ventricular ejection time), and hemodynamic parameters (stroke volume, cardiac output) were recorded during the task trials and before and after 5-min resting periods. The participants reported their subjective workload via NASA-TLX after each task trial. Autonomic nervous system parameters derived from the above-mentioned signals, subjective workload scores, and performance indices of MATB were analyzed, and test/retest reliability was investigated. The results showed that a significant test/retest correlation was obtained for SPL for more participants than in the other parameters, although there were large individual differences.

[Effects of long term mental arithmetic on physiological parameters, subjective indices and task performances].

This study examined the effects of long term mental arithmetic on physiological parameters, subjective indices and task performances to investigate the psychophysiological changes induced by mental tasks. Fifteen male university students performed six successive trials of a ten-minute mental arithmetic task. They took a five-minute resting period before and after the tasks. CFF (Critical Flicker Fusion frequency) and subjective fatigue scores using a visual analog scale, POMS (Profiles of Mood States) and SFF (Subjective Feelings of Fatigue) were obtained after each task and resting period. The voices of participants who were instructed to speak five Japanese vowels ('a', 'i', 'u', 'e', 'o') were recorded after each block to investigate a chaotic property of vocal signals that is reported to be changed by fatigue. Subjective workload ratings were also obtained by the NASA-TLX (National Aeronautics and Space Administration-Task Load Index) after the task. Physiological signals of ECG (Electrocardiogram), PTG (Photoelectric Plethysmogram), SCL (Skin Conductance Level), TBV (Tissue Blood Volume) and Respiration were recorded for all experimental blocks. The number of answers, correct rates and average levels of task difficulty for each ten-minute task were used as task performance indices. In this experiment, the task performance did not decrease, whereas subjective fatigue increased. Activation of the sympathetic nervous system was suggested by physiological parameters.

[Investigation on new molecular entities of drugs approved in three regions, Japan, U.S. and EU--common and preceding approvals in current 4 years].

The number of new molecular entities (NMEs) approved in 2005 was 17 in Japan, 20 in US and 18 in EU, respectively. Among 53 NMEs approved in Japan and at least one other region during 2002 to 2005, 53 NMEs had been approved in US and 25 in EU by 2005, but there were no common approvals only between Japan and EU. On the other hand, 26 NMEs were solely approved in US and EU during this period. Among 79 NMEs approved in either two or three regions, the number of preceding NMEs was 3 in Japan, 62 in U.S. and 14 in EU.

[Study on environmental risk assessment of drugs: excretion forms to environment].

Environmental risk assessment of human pharmaceuticals is needed to protect aquatic life from the toxic exposure because unaltered drugs and/or the metabolites are released to environment after human use. Application for new drugs shall be accompanied by an evaluation report of environmental risk assessment on basis of predicted use volume, already in US and near future in EU. In Japan, the specialists are reviewing methodology of environmental risk assessment of drugs now. To provide the basic information, we investigated excretion forms of drugs after human use for two groups of Japanese drugs; high sale products top 20 in the 2004 fiscal year and new molecular entities approved in 2004 and 2005. The assessment targets are materials produced for direct use in US, but those are active substances or active metabolites, excluding orphan drugs, vitamins, amino acids, peptides and proteins, in EU. According to EU condition, almost two thirds of 20 high sale products and one third of recently approved new molecular entities were identified to be the targets for environmental risk assessment.

Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK).

OBJECTIVE: Ca antagonists are one of the most popular classes of drugs used to treat hypertension and angina. These drugs may interact with either CYP3A4 or MDR-1 substrates, with the degree of interaction differing with each drug. We carried out a literature search to examine and compare the extent to which crucial pharmacokinetic (PK) information is included in package inserts (PIs) in Japan, USA and the UK. METHODS: A MEDLINE search from 1966 to November 2004 was undertaken with the aim of identifying studies on clinical PK drug interactions between seven Ca antagonists that are available in three countries and three CYP3A4 inhibitors (erythromycin, itraconazole and cimetidine), a CYP3A4 inhibitory food, grapefruit juice (GFJ) and the MDR-1 substrate, digoxin. The current PIs for Ca antagonists were obtained from the website of the regulatory authorities or the electronic Medicines Compendium. RESULTS: Of all possible combinations of seven Ca antagonists with three CYP3A4 inhibitor drugs, drug interaction information was available in the literature on nine combinations: Seven of these were listed in the USA PIs, two in the UK PIs, and none in the Japanese PIs. Interaction studies with GFJ were reported for every Ca antagonist; PIs in the USA provided quantitative data for four of these interactions, whereas UK PIs provided quantitative data for only one of the interactions and Japanese PIs provided no quantitative information. The PK data of co-medication of digoxin with Ca antagonists have been reported for every Ca antagonists. The USA PIs provided quantitative data for five Ca antagonists, whereas the UK PIs provided quantitative data for three Ca antagonists and Japanese PIs provided no quantitative data. CONCLUSION: The literature search revealed that PIs in the USA provided a great deal of quantitative information on PK interactions between Ca antagonists and other drugs or GFJ. In contrast, PIs in the UK and Japan did not provide sufficient information. We conclude that crucial quantitative information on these drug interactions should be incorporated in PIs, especially in Japan and the UK, as a means of assisting healthcare providers.

[Improvement of package insert CYP information for prescription drugs marketed in Japan].

In clinical practice, one drug is frequently used in combination with one or more other drugs, rather than as a sole regimen, and therefore healthcare providers need to carefully consider drug interactions. As mechanisms of drug interactions, metabolic enzymes of drugs are seen as one of the most likely interactive sites, where a majority of drugs are metabolized by cytochrome P450 (CYP). For this reason, providing appropriate information on CYP in package inserts is of grave importance. In fact, the package insert is the primary tool for supplying information on drugs to healthcare providers. The present study was designed to determine how many package inserts of prescription drugs marketed in Japan were providing CYP information. We searched the April 2003 version of "Drugs in Japan DB," which listed 2,022 prescription drugs, and found that only 239 package inserts (11.8%) mentioned CYP information and that only 194 (9.6%) specified CYP isozymes. To assess the improvement of package inserts, we searched "Drugs in Japan DB" from the January 2000 version to the April 2003 version. We found that CYP information had increased year by year (eg, 7.8-11.8% annually). For newly approved drugs, an analysis of the relationship between approval year and CYP information in package inserts (April 2003 version) revealed that recently approved drugs had more CYP information (eg, 45.5-51.3% of drugs in 1999-2002, compared to 6.8-26.1% in 1991-1996). A search for regulatory review documents for new drugs approved from 1999 to 2002 suggested that this recent improvement could be related to the increased number of studies identifying CYP isozymes involved in the metabolism or interaction with other drugs. Another reason for the recent improvement may be the fact that the guideline for package inserts for prescription drugs was revised in 1997, and the guidelines for drug interaction and pharmacokinetic studies were published between 1997 and 1999.

[Incremental effect and mechanism of cyclosporine on blood concentration of statins and statin package insert information in Japan].

Cyclosporine is an indispensable immunosuppressant used in organ transplant patients, who frequently manifest hyperlipidemia. Statins, which are cholesterol-lowering agents, are often combined with cyclosporine in the treatment of hyperlipidemia of organ transplant patients. Since cyclosporine is a substrate and inhibitor of CYP3A4, researchers suspect that the immunosuppressant inhibits CYP3A4-mediated metabolism of statins, leading to an increase in statin plasma concentration and infrequently resulting in rhabdomyolysis. However, a number of clinical trials have shown cyclosporine to increase the plasma concentration of all developed statins, including those not metabolized by CYP3A4. Furthemore, recent mechanistic studies have shown organic anion transporting peptides (OATP) C to mediate the uptake of some statins and cyclosporine has been shown to inhibit the uptake via OATP-C in cultured cells. Therefore, the inhibition of hepatic uptake of statins is considered to be one of the mechanisms by which cyclosporine incrementally increases statin blood concentration. However, most current Japanese package inserts of statins give no information on change in pharmacokinetic parameters such as AUC and Cmax in the combined medication with cyclosporine. Furthermore, in the Japanese package inserts, it is either stated that cyclosporine inhibits CYP3A4-mediated metabolism or no comment is made on the mechanism. The package insert should properly provide available quantitative information on the change of pharmacokinetic parameters and the probable mechanism of action.

[Withdrawal of cerivastatin revealed a flaw of post-marketing surveillance system in the United States].

Cerivastatin, a lipid-lowering agent, was voluntarily withdrawn from the market because of high risk of rhabdomyolysis when used as monotherapy and as comedication with fibrates, especially gemfibrozil. Thereafter, investigators found a five-fold increase in the area under the curve (AUC) when cerivastatin was used as comedication with gemfibrozil and theorized that the increase was associated with inhibition of the hepatic uptake and metabolism. By contrast, a number of pharmacoepidemiological investigations--one of which involved evaluation of the Food and Drug Administration (FDA) database for suspected adverse drug reactions and 11 cohort studies of statin and fibrate users in United States showed the risk of rhabdomyolysis to be greater in cerivastatin than in other statins used in either monotherapy or in comedication with fibrates, especially gemfibrozil. This incident regarding risk of rhabdomyolysis in cerivastatin monotherapy was taken to court in the United States and unpublished company (manufacturer of cerivastatin) documents were opened. The incident was then analyzed and discussed in the Journal of American Medical Association (JAMA) as a concern of the current US post-marketing surveillance system. The company's action and timing were judged and found to be inappropriate (although companies of this sort generally have insurmountable conflicts of interest), and the work of the US regulatory system and funding for post-marketing safety management were found to be insufficient. On the basis of the current situation, the authors and editors recommend further improvement of post-marketing regulations including the establishment of an independent drug safety board to oversee post-marketing surveillance. Among the opened, unpublished data, was the finding that cerivastatin obviously induced myopathy in a dose-dependent manner when administrated as monotherapy. As for other statins, only limited data was available for the relationship between the dosage and the rate of myopathy. For the safety use of statins, this should be clarified by proper surveillance system.

Cardiovascular reactivity to mental stress: relationship with menstrual cycle and gender.

The purpose of the present study was to determine the fluctuation in cardiovascular reactivity to mental stress during the menstrual cycle by comparing heart rate variability (HRV), and other physiological and psychological data in females with those in males. Cardiovascular reactivity to two mental tasks was measured in 14 females during the follicular and luteal phase of menstruation over two menstrual cycles. The same tasks were subsequently given to a matched pair of males (N=14), at the same intervals as their corresponding females. Heart rate, blood pressure and HRV were used as indices of cardiovascular reactivity. Subjective mental workload was measured at the end of each task. Power spectral analysis of HRV showed that the high frequency (HF) component in HRV decreased more during the luteal phase than the follicular phase. The low frequency (LF) component in HRV and the LF/HF ratio in the luteal phase were significantly higher than that in the follicular phase. The LF component and the LF/HF ratio were significantly lower in females than in males; conversely, the HF component was significantly higher in females than in males. Neither significant effects of menstrual cycle, gender and mental stress nor any significant interactions were found for mental workload. These findings indicate that sympathetic nervous activity in the luteal phase is significantly greater than in the follicular phase whereas parasympathetic nervous activity is predominant in the follicular phase. The results also suggest that predominance of sympathetic nervous activity in males compared with a dominant parasympathetic nervous activity in females.