Shigeki Takemura

A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood

Although a measurable number of epidemiological studies have been conducted to clarify the associations between mercury exposure during embryo or early infancy and later incidences of autism spectrum disorders (ASD) or attention-deficit hyperactivity disorder (ADHD), the conclusion still remains unclear. Meta-analysis was conducted for two major exposure sources; i.e., thimerosal vaccines that contain ethylmercury (clinical exposure), and environmental sources, using relevant literature published before April 2014. While thimerosal exposures did not show any material associations with an increased risk of ASD or ADHD (the summary odds ratio (OR) 0.99, 95% confidence interval (CI) 0.80-1.24 for ASD; OR 0.91, 95% CI 0.70-1.13 for ADHD/ADD), significant associations were observed for environmental exposures in both ASD (OR 1.66, 95% CI 1.14-2.17) and ADHD (OR 1.60, 95% CI 1.10-2.33). The summary ORs were similar after excluding studies not adjusted for confounders. Moderate adverse effects were observed only between environmental inorganic or organic mercury exposures and ASD/ADHD. However, these results should be interpreted with caution since the number of epidemiological studies on this issue was limited and still at an early stage. Further studies focused on subjects with genetic vulnerabilities of developmental disorders are warranted for better understanding of the effects of such environmental exposures.

Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression.

BACKGROUND The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. MATERIALS AND METHODS Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. RESULTS The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients (P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients (P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis (P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. CONCLUSIONS The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.

Genetic alcohol sensitivity regulated by ALDH2 and ADH1B polymorphisms is strongly associated with depression and anxiety in Japanese employees

BACKGROUND Although alcohol-related disorders (ARD) have been shown to be accompanied by comorbid depressive and anxiety disorders, and alcohol metabolic enzyme genes, ADH1B and ALDH2 polymorphisms, have been associated with an increased risk of ARD, no studies have been conducted to evaluate the associations between these genetic polymorphisms and anxiety or depression. METHOD A total of 1944 Japanese workers were interviewed regarding their depressive and anxiety disorders, including suicidality, by a brief psychiatric structured interview (MINI). We investigated the relationship of ADH1B rs1229984 and ALDH2 rs671 polymorphism combinations with mental disorder risks. Logistic regression analysis was used to evaluate the associations between those polymorphisms and anxiety/depressive disorders, adjusting for sex, age, and job rank. The degree of alcohol sensitivity was classified into five groups according to the combination of two enzyme genotypes (Group I-V, in order from the lowest alcohol sensitivity). RESULTS Those with ALDH2(*)1/(*)1 and ADH1B(*)1/(*)1 were likely to be at an increased risk of depressive and anxiety disorders as well as ARD. This tendency was more apparent among non-drinkers (OR 9.20, 95% CI 1.66-50.89). No adverse effects of ALDH2 or ADH1B alone were observed with mental disorder risks. Likewise, analyses conducted combining job rank and genetic alcohol sensitivity showed no material associations with such risks. CONCLUSIONS Genetic alcohol sensitivity, especially that with the genotype combination of ALDH2(*)1/(*)1 and ADH1B(*)1/(*)1, was significantly associated with an increased risk of depressive and anxiety disorders as well as ARD.

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment

Objectives The dose–response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose–response relationship of HAVS in a tropical environment. Methods A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses—lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)—were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. Results The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m2 s−4 against those <16 ln m2 s−4. Similar dose–response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. Conclusions The dose–response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose–response pattern of a heterogeneous group of vibratory tools workers.

EphA4-deleted microenvironment regulates cancer development and leukemoid reaction of the isografted 4T1 murine breast cancer via reduction of an IGF1 signal

EphA4 belongs to the largest family of receptor tyrosine kinases (RTKs). Although EphA4 is highly expressed in the central nervous system, EphA4 has also been implicated in cancer progression. Most of the studies focus on the expression and function in tumor cells. It is unknown whether EphA4‐deleted microenvironment affects tumor progression. Some of cancers in animals and humans, such as 4T1 cancer cells, are known to produce a large amount of granulocyte colony‐stimulating factors (G‐CSF/Csf3) which can stimulate myeloproliferation, such as myeloid‐derived suppressor cells (MDSCs) leading to a poor recipient prognosis. We isografted 4T1 breast cancer cells into both EphA4‐knockout and control wild‐type female littermate mice. The results showed that the EphA4‐deleted host could inhibit primary tumor growth and tumor metastasis mainly by decreasing the amount of IGF1 synthesis in the circulation and locally tissues. The EphA4‐deleted microenvironment and delayed tumor development reduced the production of G‐CSF resulting in the decrease of splenomegaly and leukemoid reaction including MDSCs, which in turn inhibit the tumor progression. This inhibition can be reversed by supplying the mice with IGF1. However, an excess of IGF1 supply over demand to the control mice could not further accelerate the tumor growth and metastasis. A better understanding and re‐evaluation of the main role of IGF1 in regulating tumor progression could further enhance our cognition of the tumor development niche. Our findings demonstrated that EphA4‐deleted microenvironment impairs tumor‐supporting conditions. Conclusion: Host EphA4 expression regulates cancer development mainly via EphA4‐mediated IGF1 synthesis signal. Thus, targeting this signaling pathway may provide a potential therapeutic option for cancer treatment.

Short stick exercises for fall prevention among older adults: a cluster randomized trial

Abstract Purpose: To investigate the effects of short stick exercise (SSEs) on fall prevention and improvement of physical function in older adults. Methods: A cluster randomized trial was conducted in five residential care facilities. The intervention group (n = 51) practiced SSEs for six months, followed by routine care for six more months. The control group (n = 54) received ordinary care for 12 months. The primary outcome measure was the number of fallers, taking into account the time to first fall using the Kaplan–Meier method. The secondary outcome measures were physical and mental functions. Results: The number of fallers was significantly lower in the intervention group (n = 6) than in the control group (n = 16) during the 12 months. The adjusted hazard ratio for a first fall in the intervention group compared with the control group was 0.15 (CI, 0.03 to 0.74, p = 0.02). The fall-free period was significantly longer in the intervention group than in controls (mean ± SD, 10.1 ± 3.0 versus 9.0 ± 4.1 months, p = 0.027). The functional reach and sit and reach tests were significantly improved at three and six months. Conclusion: The SSEs appeared effective for fall prevention and improvement of physical function in older adults. Implications for Rehabilitation The newly developed short stick exercises appear an effective means of reducing falls among older adults in residential care facilities. The short stick exercises seem to have an immediate effect on improving physical functions. Effects gained by performing the short stick exercises, such as static balance, flexibility and agility may last for six months. The short stick exercises were found to be easy for older adults to practice continuously in residential care facilities.

Linking lifestyle factors and insulin resistance, based on fasting plasma insulin and HOMA-IR in middle-aged Japanese men: A cross-sectional study

Abstract Objective. Insulin resistance (IR) is regarded as one of the earliest features of many metabolic diseases, and major efforts are aimed at improving insulin function to confront this issue. The aim of this study was to investigate the relationship of body mass index (BMI), cigarette smoking, alcohol intake, physical activity, green tea and coffee consumption to IR. Methods. We performed a cross-sectional study of 1542 male self defense officials. IR was defined as the highest quartile of the fasting plasma insulin (≥ 50 pmol/L) or the homeostasis model assessment-estimated IR (HOMA-IR ≥ 1.81). An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between IR and influential factors. Stratified analysis by obesity status (BMI < 25 kg/m2, non-obese; ≥ 25 kg/m2, obese) was performed. Results. IR was significantly positively related to BMI and glucose tolerance, negatively related to alcohol use. Independent of obesity status, significant trends were observed between IR and alcohol use. Drinking 30 mL or more of ethanol per day reduced IR by less than 40%. Strong physical activity was associated with decreased risk of IR based on fasting plasma insulin only in the obese. Coffee consumption was inversely associated with the risk of IR based on HOMA-IR in the non-obese group. Conclusion. Higher coffee consumption may be protective against IR among only the non-obese. Further studies are warranted to examine the effect modification of the obesity status on the coffee-IR association.

A Comparison of Hand-arm Vibration Syndrome between Malaysian and Japanese Workers

A Comparison of Hand‐arm Vibration Syndrome between Malaysian and Japanese Workers: Anselm Ting SU, et al. Centre for Occupational and Environmental Health, Department of Social and Preventive Medicine, University of Malaya, Malaysia—The evidence on hand‐arm vibration syndrome (HAVS) in tropical environments is limited. The legislation for the control of occupational vibration exposure has yet to be established in Malaysia.

Validity of a Diagnostic Scale for Acupuncture: Application of the Item Response Theory to the Five Viscera Score

In acupuncture therapy, diagnosis, acupoints, and stimulation for patients with the same illness are often inconsistent among between Traditional Chinese Medicine (TCM) practitioners. This is in part due to the paucity of evidence-based diagnostic methods in TCM. To solve this problem, establishment of validated diagnostic tool is inevitable. We first applied the Item Response Theory (IRT) model to the Five Viscera Score (FVS) to test its validity by evaluating the ability of the questionnaire items to identify an individuals latent traits. Next, the health-related QOL scale (SF-36), a suitable instrument for evaluating acupuncture therapy, was administered to evaluate whether the FVS can be used to make a health-related diagnosis. All 20 items of the FVS had adequate item discrimination, and 13 items had high item discrimination power. Measurement accuracy was suited for application in a range of individuals, from healthy to symptomatic. When the FVS and SF-36 were administered to other subjects, a part of which overlap with the first subjects, we found an association between the two scales, and the same findings were obtained when symptomatic and asymptomatic subjects were compared regardless of age and sex. In conclusion, the FVS may be effective in clinical diagnosis.

Associations between anthropometric factors and peripheral neuropathy defined by vibrotactile perception threshold among industrial vibrating tool operators in Japan.

The effect of anthropometric factors on the fingertip vibrotactile perception threshold (VPT) of industrial vibrating tool operators (IVTOs) is not well known. The purpose of this study was to investigate the associations between anthropometric factors and fingertip VPT.