A multi-satellite framework to rapidly evaluate extreme biosphere cascades: The Western US 2021 drought and heatwave.

The increasing frequency and intensity of climate extremes and complex ecosystem responses motivate the need for integrated observational studies at low latency to determine biosphere responses and carbon-climate feedbacks. Here, we develop a satellite-based rapid attribution workflow and demonstrate its use at a 1-2-month latency to attribute drivers of the carbon cycle feedbacks during the 2020-2021 Western US drought and heatwave. In the first half of 2021, concurrent negative photosynthesis anomalies and large positive column CO2 anomalies were detected with satellites. Using a simple atmospheric mass balance approach, we estimate a surface carbon efflux anomaly of 132 TgC in June 2021, a magnitude corroborated independently with a dynamic global vegetation model. Integrated satellite observations of hydrologic processes, representing the soil-plant-atmosphere continuum (SPAC), show that these surface carbon flux anomalies are largely due to substantial reductions in photosynthesis because of a spatially widespread moisture-deficit propagation through the SPAC between 2020 and 2021. A causal model indicates deep soil moisture stores partially drove photosynthesis, maintaining its values in 2020 and driving its declines throughout 2021. The causal model also suggests legacy effects may have amplified photosynthesis deficits in 2021 beyond the direct effects of environmental forcing. The integrated, observation framework presented here provides a valuable first assessment of a biosphere extreme response and an independent testbed for improving drought propagation and mechanisms in models. The rapid identification of extreme carbon anomalies and hotspots can also aid mitigation and adaptation decisions.

Associations of circulating xanthine oxidoreductase activity with cardiometabolic risk markers in overweight and obese Japanese men: a cross-sectional pilot study.

Circulating xanthine oxidoreductase (XOR) activity may contribute to the pathogenesis of obesity-related adverse cardiometabolic profiles. This pilot study aimed to examine the cross-sectional associations between plasma XOR activity and cardiometabolic risk (CMR) markers in overweight and obese men. In 64 overweight and obese Japanese men (aged 31-63 years), plasma XOR activity and several CMR markers, such as homeostasis model assessment of insulin resistance (HOMA-IR), and clustered CMR score were measured in each participant. Clustered CMR score was constructed based on waist circumference, triglyceride, blood pressure, fasting plasma glucose, and high-density lipoprotein cholesterol. Plasma XOR activity in overweight and obese men was positively associated with the body mass index, waist circumference, visceral fat area, body fat mass, hemoglobin A1c, serum 8-hydroxy-2'-deoxyguanosine, HOMA-IR, and clustered CMR score and was inversely associated with handgrip strength and high-density lipoprotein cholesterol. Multiple linear regression analysis further demonstrated that the associations of plasma XOR activity with HOMA-IR and the clustered CMR score remained significant after adjustment for covariates including uric acid. Our data demonstrate that circulating XOR activity was independently associated, albeit modestly, with HOMA-IR and the clustered CMR score. These preliminary findings suggest that circulating XOR activity can potentially be one of the preventive targets and biomarkers of cardiometabolic disorders in over-weight and obese men.

One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

Plasma free metanephrine and normethanephrine levels correlated to plasma catecholamine after acute running in amateur runner.

BACKGROUND: Catecholamine is a typical index of exercise intensity, but it is difficult to detect. Plasma metanephrine (MN) and normethanephrine (NMN) levels are more stable than those of catecholamines. This study aimed to investigate plasma MN and NMN levels during acute exercise running in amateur runners. METHODS: Samples were collected from eight healthy male participants. They were either sedentary or running at low or high intensity for 30 min. Blood samples were collected under these conditions. Measurements taken included plasma adrenaline, noradrenaline, MN, and NMN. RESULTS: Plasma adrenaline levels increased after high-intensity exercise compared with sedentary subjects. Plasma noradrenaline, MN, and NMN levels increased after both low- and high-intensity exercise compared with sedentary subjects. In addition, these levels were also significantly higher at high intensity than at low intensity. Plasma adrenaline and noradrenaline levels were positively correlated with plasma free MN and NMN levels after acute running, respectively. CONCLUSION: This study revealed that plasma MN and NMN levels transiently increased depending on exercise intensity in amateur runners. In addition, plasma NMN levels are better markers than plasma MN levels because of their stronger correlation with plasma catecholamine levels.

Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy.

Local cryotherapy is widely used as a treatment for sports-related skeletal muscle injuries. The molecular mechanisms are unknown. To clarify these mechanisms, we applied one to three 15-min cold stimulations at 4 °C to various cell lines (in vitro), the tibialis anterior (TA) muscle (ex vivo), and mouse limbs (in vivo). In the in vitro assay, cyclic AMP (cAMP) response element binding protein 1 (CREB1) was markedly phosphorylated (p-CREB1), and the CREB-binding protein (CBP) was recruited to p-CREB-1 in response to two or three cold stimulations. In a reporter assay with the cAMP-responsive element, the signals significantly increased after two to three cold stimulations at 4 °C. In the ex vivo study, CREB-targeting genes were significantly upregulated following two or three cold stimulations. The in vivo experiment disclosed that cold stimulation of a mouse limb for 9 days significantly increased mitochondrial DNA copy number and upregulated genes involved in mitochondrial biogenesis. The results suggest that local cryotherapy increases CREB transcription and upregulates CREB-targeting genes, in a manner dependent on cold stimulation frequency and duration. This information will inform further investigations into local cryotherapy as a treatment for sports-related skeletal muscle trauma.

Global relationships among traditional reflectance vegetation indices (NDVI and NDII), evapotranspiration (ET), and soil moisture variability on weekly timescales.

Monitoring the effects of water availability on vegetation globally using satellites is important for applications such as drought early warning, precision agriculture, and food security as well as for more broadly understanding relationships between water and carbon cycles. In this global study, we examine how quickly several satellite-based indicators, assumed to have relationships with water availability, respond, on timescales of days to weeks, in comparison with variations in root-zone soil moisture (RZM) that extends to about 1 m depth. The satellite indicators considered are the normalized difference vegetation and infrared indices (NDVI and NDII, respectively) derived from reflectances obtained with moderately wide (20-40 nm) spectral bands in the visible and near-infrared (NIR) and evapotranspiration (ET) estimated from thermal infrared observations and normalized by a reference ET. NDVI is primarily sensitive to chlorophyll contributions and vegetation structure while NDII may contain additional information on water content in leaves and canopy. ET includes both the loss of root zone soil water through transpiration (modulated by stomatal conductance) as well as evaporation from bare soil. We find that variations of these satellite-based drought indicators on time scales of days to weeks have significant correlations with those of RZM in the same water-limited geographical locations that are dominated by grasslands, shrublands, and savannas whose root systems are generally contained within the 1 m RZM layer. Normalized ET interannual variations show generally a faster response to water deficits and enhancements as compared with those of NDVI and NDII, particularly in sparsely vegetated regions.

Lifestyle intervention using Internet of Things (IoT) for the elderly: A study protocol for a randomized control trial (the BEST-LIFE study).

Modification of lifestyle habits, including diet and physical activity, is essential for the prevention and control of type 2 diabetes mellitus (T2DM) in elderly patients. However, individualized treatment is more critical for the elderly than for general patients. This study aimed to determine lifestyle interventions that resulted in lowering hemoglobin A1c (HbA1c) in Japanese pre- and early diabetic elderly subjects. The BEST-LIFE trial is an ongoing, open-label, 6-month, randomized (1:1) parallel group trial. Subjects with HbA1c of ≥5.6%-randomly assigned to the intervention or control group -use wearable monitoring devices loaded with Internet of things (IoT) systems that aids them with self-management and obtaining monthly remote health guidance from a public health nurse. The primary outcome is changes in HbA1c after a 6-month intervention relative to the baseline values. The secondary outcome is the change of behavior modification stages. The background, rationale, and study design of this trial are also presented. One hundred forty-five subjects have already been enrolled in this lifestyle intervention program, which will end in 2019. The BEST-LIFE trial will provide new evidence regarding the effectiveness and safety of our program on lowering HbA1c in elderly subjects with T2DM. It will also investigate whether information communication technology tools and monitoring devices loaded with IoT can support health care in elderly subjects. The trial registration number is UMIN-CTR: UMIN 000023356.

Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers.

BACKGROUND: Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). METHODS: This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. RESULTS: BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). CONCLUSION: The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

Perception and attitude of medical doctors in Dhaka, Bangladesh, with regard to Ayurvedic medicine.

The World Health Organization (WHO) Traditional Medicine Strategy (2014-2023) aimed to help member states promote the safe and effective use of traditional medicine. While economic conditions have markedly improved in Bangladesh, the country is experiencing significant public health problems. Because of limited medical resources, there is a strong incentive to enhance complementary and alternative medicine usage in Bangladesh. Therefore, this study aimed to confirm the perceptions and attitudes of medical doctors (MDs) in Dhaka, Bangladesh, with regard to Ayurvedic medicine (AM). A total number of 159 MDs in Dhaka were interviewed by face-to-face between February and June 2015. The study revealed that 62.0% of MDs had treated patients with AM and 55.3% believed that AM should be regarded as its own specialty, whereas 39.7% of MDs believed that AM should be part of the conventional medical curriculum and 32.7% thought that AM did not seem scientific. In terms of gender, 45.3% of male MDs agreed or strongly agreed that AM only had a placebo effect. On the other hand, 65.8% of female MDs disagreed or strongly disagreed it. In terms of age, 77.0% of MDs aged 36 or elder (elder MDs) believed they were more likely to recommend AM use and 80.3% of elder MDs believed that the government should encourage more initiatives to promote AM. To enhance AM use, scientifically robust information on the efficacy, safety and scientific basis of AM should be more effectively conveyed to male MDs.

Randomized controlled trial for assessment of Internet of Things system to guide intensive glucose control in diabetes outpatients: Nagoya Health Navigator Study protocol.

The Internet of Things (IoT) allows collecting vast amounts of health-relevant data such as daily activity, body weight (BW), and blood pressure (BP) automatically. The use of IoT devices to monitor diabetic patients has been studied, but could not evaluate IoT-dependent effects because health data were not measured in control groups. This multicenter, open-label, randomized, parallel group study will compare the impact of intensive health guidance using IoT and conventional medical guidance on glucose control. It will be conducted in outpatients with type 2 diabetes for a period of 6 months. IoT devices to measure amount of daily activity, BW, and BP will be provided to IoT group patients. Healthcare professionals (HCPs) will provide appropriate feedback according to the data. Non-IoT control, patients will be given measurement devices that do not have a feedback function. The primary outcome is glycated hemoglobin at 6 months. The study has already enrolled 101 patients, 50 in the IoT group and 51 in the non-IoT group, at the two participating outpatient clinics. The baseline characteristics of two groups did not differ, except for triglycerides. This will be the first randomized, controlled study to evaluate IoT-dependent effects of intensive feedback from HCPs. The results will validate a new method of health-data collection and provision of feedback suitable for diabetes support with increased effectiveness and low cost.

Level of perception of technical terms regarding the effect of radiation on the human body by residents of Japan.

BACKGROUND: This study aimed to examine the level of perception of the technical terms related to the effect of radiation on the human body among residents of the six prefectures of Miyagi, Fukushima, Tokyo, Aichi, Hiroshima, and Nagasaki in Japan. Miyagi and Fukushima were selected as devastated area by Great East Japan Earthquake. Tokyo and Aichi were selected as control. Hiroshima and Nagasaki were selected as the A-bombed area. METHODS: A total of 1030 respondents, 172, 173, 171, 173, 171, and 170, respectively, were surveyed. Differences in the recognition level of technical terms related to the effect of radiation on the human body among residents of the six prefectures were assessed. RESULTS: The highest recognition levels were reported by the respondents from Fukushima (17 items). Those from Miyagi scored the second highest recognition levels (10 out of the 17 terms); the second highest recognition levels for the remaining seven terms were marked by the respondents of Tokyo. Respondents in the Tohoku region had a better recognition for the technical terminology relevant to the effect of radiation on the human body. CONCLUSIONS: Our findings indicate a need for continued, comprehensive risk communication pertaining to health hazards of radiation exposure in Tohoku region. Concerted efforts by central/local governments and other stakeholders are required to allay the anxiety/stress related to radiation exposure among the residents.

Development of quantitative immunochromatographic kit and visual screening immunoassay strip for cadmium.

Cadmium is a highly toxic heavy metal for humans. In 2006, the Codex Alimentarius Commission set the international standard value of Cd contained in polished rice at 0.4 mg kg(-1), thus requiring the monitoring of Cd in food. We developed two types of Cd immunochromatographic kit by using anti-(Cd-EDTA) antibody. One is the quantitative Cd immunochromatographic device which can precisely measure Cd concentrations. The other is the Cd screening strip that enables visible evaluation of Cd exceeding 0.003 mg L(-1). Compared with conventional instrumental analysis methods, the immunoassay kits provide rapid, simple, and inexpensive on-site methods. For these kits, we also developed an efficient pretreatment method that can be easily administrated on-site. In this method, brown rice samples are coarsely crushed by a hand-held grinder then mixed with an enzyme solution, and Cd is extracted with HCl. The extracted solution is then purified by a newly developed Cd-selective ion exchange column. Cd concentrations measured by the quantitative Cd immunochromatographic devices correlated well with those obtained by ICP-OES (r (2) = 0.96). The Cd screening strips performed well in tests; pretreated purification solution which gave Cd concentrations exceeding 0.4 mg kg(-1) according to the Cd immunochromatographic devices gave corresponding results with the Cd screening strips with no false positives or false negatives. These results indicate that the two immunochromatographic kits are useful for on-site measurement of Cd concentrations and screening of Cd present in brown rice.

Perceptions of Ayurvedic medicine by citizens in Dhaka, Bangladesh.

Bangladesh is now facing the public health problems of deficiency of iron and iodine, especially for women. The Ministry of Health and Family Welfare of Bangladesh has implemented strong countermeasures to enhance the health condition of the nation. On the other hand, based on the concept of the Declaration of Alma-Ata, complementary and alternative medicine should be used more vigorously to enhance public health in the world. The usage of complementary and alternative medicine such as ayurvedic medicine (AM) should be increased in Bangladesh. Therefore we conducted the study on perceptions of AM by citizens in Dhaka, Bangladesh in order to promote and enhance the effective usage of AM, including herbal medicines as medical resources, from December 2010 to January 2011. This study showed younger citizens (61.1%) did not get more benefit from AM than elder citizens (48.0%). On the other hand, younger citizens (76.8%) did not get more harm from AM than elder citizens (70.1%). We think that in terms of effectiveness of AM, the younger generation in Dhaka seems to be more skeptical to AM than the elder generation in Dhaka, even though the younger generation are more satisfied with AM than the elder generation. With viewpoint of enhancement of usage of AM in Dhaka, we think that scientifically sound information on AM should be collected rigorously and brought to the citizens vigorously to remove the skeptical feeling of AM from younger citizen in Dhaka. In terms of the effective utilization of limited medical resources, AM should be used appropriately in Bangladesh, Asia and the world.

Patients' level of medical term recognition as estimated by healthcare workers.

To render risk communication between patients and healthcare workers more effective, gaps in the patients' level of medical term recognition as estimated by healthcare workers was examined. This was a cross-sectional study conducted via an Internet survey. A total of 244 nurses and 211 medical doctors were surveyed. We examined 90 medical terms, including 57 medical terms examined by the National Institute for Japanese Language and 33 newly added medical terms. Differences between medical doctors and nurses with respect to the estimation of patients' level of medical term recognition were assessed. The level of medical term recognition by patients was higher when estimated by nurses than when estimated by medical doctors. As members of team care, nurses must consider that patients find technical medical terms to be more difficult than anticipated and that patients are aware of these terms only to a certain extent while receiving healthcare information, such as drug information. Currently, nurses are expected to perform activities as clinical research coordinators and also are requested to work as home-visiting nurses. Therefore they also need ensure that patients understand the medical information provided to them.

Patient's recognition level of medical terms as estimated by pharmacists.

OBJECTIVES: The role of pharmacists in the healthcare settings is expanding and pharmacists are expected to counsel patients and/or caregivers regarding the appropriate use of a drug. However, we believe that communication between healthcare providers and patients may be limited by overestimation of patients' recognition level of medical terms by providers. The purpose of this study was to clarify patients' recognition level of medical terms, mainly related to drugs, as estimated by pharmacists to contribute to improving risk communication in the medical care field. METHODS: A total of 211 medical doctors and 212 pharmacists were surveyed. Differences between patients' recognition level of medical terms as estimated by medical doctors and pharmacists were assessed. In total, 90 medical terms were evaluated, including 57 medical terms from the National Institute for Japanese Language and an additional 33 medical terms. RESULTS: Patient's recognition level of the selected medical terms as estimated by pharmacists was higher than that estimated by medical doctors. CONCLUSIONS: Compared with medical doctors, pharmacists tend to overestimate patients' recognition level of medical terms. Therefore, pharmacists need to take greater care to ensure that their patients fully understand the risks and benefits of the drugs.

Identification of a novel biomarker for sarcopenia diagnosis using serum metabolomic analysis: a pilot study.

PURPOSE: This pilot study compared serum metabolites in participants with and without sarcopenia. METHODS: Metabolomic techniques were applied to identify serum metabolites and novel biomarkers specific to patients with sarcopenia. In accordance with AWGS2019 criteria, sarcopenia was defined as low muscle mass plus either low muscle strength/low physical function, and severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical function all together. RESULTS: The sarcopenia group had higher hypoxanthine, galactose, and mannose levels but lower triethanolamine and homogentisic acid levels than the non-sarcopenia group. The severe sarcopenia group had lower levels of alpha-tocopherol than the mild and moderate sarcopenia groups. CONCLUSION: This study is the first to identify hypoxanthine as a potential biomarker for sarcopenia in humans and provides new insights into the pathophysiology of sarcopenia. Furthermore, the identified metabolites may be useful for the early detection of sarcopenia.

Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas.

To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy.

Current situation of clinical trials in Beijing and Shanghai, China.

OBJECTIVE: Global clinical trials are important because they facilitate rapid delivery of new and effective drugs to patients Assessment of the current situation of clinical trials conducted in Asia is critical for improving performance of global clinical trials. However, review reports from China or other Asian countries are not yet available. Therefore, the purpose of this research was to investigate the current quality of clinical trials conducted in Shanghai, as well as Beijing. METHODS: Questionnaires were distributed to medical doctors attending institutes in Beijing and Shanghai in which clinical trials have been conducted. These questionnaires were delivered and collected from both areas by the Peking University research team of Beijing and the Fudan University research team of Shanghai respectively. Analysis and evaluation were conducted by research teams from both China and Japan. RESULTS: Subjects were randomly selected by the respective research team. A total of 145 questionnaires in Beijing and 162 in Shanghai were administered: all 307 questionnaires were completed. In total, 57.2% and 74.5% of respondents from Beijing and Shanghai, respectively, reported participation in audits and inspections on an annual basis conducted by their own institute. A total of 49.2% and 56.0% of respondents from Beijing and Shanghai, respectively, reported that they received reports after the audits and inspections by an institute. 23.5% and 37.7% of respondents from Beijing and Shanghai, respectively, reported participation in audits conducted annually by external authorities. A total of 18.9% and 29.5% of respondents from Beijing and Shanghai, respectively, reported that they received reports after the audits and inspections by an external authority. CONCLUSIONS: Our research suggests that clinical trials in Shanghai, as well as in Beijing, are conducted vigorously and appropriately monitored by audits and inspections conducted by concerned institutes and/or by an external authority.

Bulge-like asymmetric heterodye clustering in DNA duplex results in efficient quenching of background emission based on the maximized excitonic interaction.

Asymmetric dye clusters with a single fluorophore (Cy3) and multiple quenchers (4'-methylthioazobenzene-4-carboxylate, methyl red, and 4'-dimethylamino-2-nitroazobenzene-4-carboxylate) were prepared. The dye and one-to-five quenchers were tethered through D-threoninol to opposite strands of a DNA duplex. NMR analysis revealed that the clusters with a single fluorophore and two quenchers formed a sandwich-like structure (antiparallel H-aggregates). The melting temperatures of all the heteroclusters were almost the same, although structural distortion should become larger, as the number of quenchers increased. An asymmetric heterocluster of a single fluorophore and two quenchers showed larger excitonic interaction (i.e., hypochromicity of Cy3), than did a single Cy3 and a single quencher. Due to the larger exciton coupling between the dyes, the 1:2 heterocluster suppressed the background emission more efficiently than the 1:1 cluster. However, more quenchers did not enhance quenching efficiency due to the saturation of exciton coupling with two quenchers. Finally, this asymmetric 1:2 heterocluster was introduced into the stem region of a molecular beacon (MB; also known as an in-stem MB) targeting the fusion site in the L6 BCR-ABL fusion gene. With this MB design, the signal/background ratio was as high as 68 due to efficient suppression of background emission resulting from the maximized excitonic interaction.

Combinational risk factors of metabolic syndrome identified by fuzzy neural network analysis of health-check data.

BACKGROUND: Lifestyle-related diseases represented by metabolic syndrome develop as results of complex interaction. By using health check-up data from two large studies collected during a long-term follow-up, we searched for risk factors associated with the development of metabolic syndrome. METHODS: In our original study, we selected 77 case subjects who developed metabolic syndrome during the follow-up and 152 healthy control subjects who were free of lifestyle-related risk components from among 1803 Japanese male employees. In a replication study, we selected 2196 case subjects and 2196 healthy control subjects from among 31343 other Japanese male employees. By means of a bioinformatics approach using a fuzzy neural network (FNN), we searched any significant combinations that are associated with MetS. To ensure that the risk combination selected by FNN analysis was statistically reliable, we performed logistic regression analysis including adjustment. RESULTS: We selected a combination of an elevated level of γ-glutamyltranspeptidase (γ-GTP) and an elevated white blood cell (WBC) count as the most significant combination of risk factors for the development of metabolic syndrome. The FNN also identified the same tendency in a replication study. The clinical characteristics of γ-GTP level and WBC count were statistically significant even after adjustment, confirming that the results obtained from the fuzzy neural network are reasonable. Correlation ratio showed that an elevated level of γ-GTP is associated with habitual drinking of alcohol and a high WBC count is associated with habitual smoking. CONCLUSIONS: This result obtained by fuzzy neural network analysis of health check-up data from large long-term studies can be useful in providing a personalized novel diagnostic and therapeutic method involving the γ-GTP level and the WBC count.