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1.  Association Between 17q12-21 Variants and Asthma in Japanese Women: rs11650680 Polymorphism as Potential Genetic Marker for Asthma 
DNA and Cell Biology  2014;33(8):531-536.
Epidemiological evidence on the relationship between single-nucleotide polymorphisms (SNPs) rs7216389 and rs11650680 on chromosome 17q12-21 and asthma is inconsistent. We examined this issue in young adult Japanese women. Case subjects were 202 women who had been diagnosed with asthma by a doctor, while 1290 women without doctor-diagnosed asthma served as control subjects. Adjustments were made for age and the presence of older siblings. There were no significant associations between SNP rs7216389 and asthma. Compared with the CC genotype of SNP rs11650680, the CT genotype, but not the TT genotype, was significantly inversely associated with asthma: the adjusted odds ratio for the CT genotype was 0.67 (95% confidence interval: 0.46–0.96). This inverse relationship was significant in women with late-onset asthma, but not in those with early-onset asthma. Under the dominant model, a significant inverse association was found between rs11650680 and asthma in women without older siblings, but not in those with older siblings; the interaction, however, was not significant. This is the first study to show that the CT genotype of SNP rs11650680 was significantly inversely associated with asthma, especially adult-onset asthma. We could not find evidence for interactions between rs11650680 and older siblings affecting asthma.
doi:10.1089/dna.2014.2387
PMCID: PMC4117259  PMID: 24735179
2.  Detection of Nonverbal Synchronization through Phase Difference in Human Communication 
PLoS ONE  2015;10(7):e0133881.
Nonverbal communication is an important factor in human communication, and body movement synchronization in particular is an important part of nonverbal communication. Some researchers have analyzed body movement synchronization by focusing on changes in the amplitude of body movements. However, the definition of “body movement synchronization” is still unclear. From a theoretical viewpoint, phase difference is the most important factor in synchronization analysis. Therefore, there is a need to measure the synchronization of body movements using phase difference. The purpose of this study was to provide a quantitative definition of the phase difference distribution for detecting body movement synchronization in human communication. The phase difference distribution was characterized using four statistical measurements: density, mean phase difference, standard deviation (SD) and kurtosis. To confirm the effectiveness of our definition, we applied it to human communication in which the roles of speaker and listener were defined. Specifically, we examined the difference in the phase difference distribution between two different communication situations: face-to-face communication with visual interaction and remote communication with unidirectional visual perception. Participant pairs performed a task supposing lecture in the face-to-face communication condition and in the remote communication condition via television. Throughout the lecture task, we extracted a set of phase differences from the time-series data of the acceleration norm of head nodding motions between two participants. Statistical analyses of the phase difference distribution revealed the characteristics of head nodding synchronization. Although the mean phase differences in synchronized head nods did not differ significantly between the conditions, there were significant differences in the densities, the SDs and the kurtoses of the phase difference distributions of synchronized head nods. These results show the difference in nonverbal synchronization between different communication types. Our study indicates that the phase difference distribution is useful in detecting nonverbal synchronization in various human communication situations.
doi:10.1371/journal.pone.0133881
PMCID: PMC4514884  PMID: 26208100
3.  Relationship Between IL1 Gene Polymorphisms and Periodontal Disease in Japanese Women 
DNA and Cell Biology  2014;33(4):227-233.
Epidemiological evidence on the relationship between IL1A and/or IL1B polymorphisms and periodontal disease is inconsistent. We investigated associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes encoding interleukin (IL) -1α (rs1800587) and IL-1β (rs1143634 and rs16944) and the risk of periodontal disease among young Japanese women. A case–control study was performed with a total of 1150 women, including 131 subjects who had at least one tooth with a probing pocket depth of 4 mm or deeper and 1019 periodontally healthy controls. Compared with a reference group of women with the GG genotype of SNP rs16944, those with the GA genotype had a significantly reduced risk of periodontal disease, while there was no significant relationship between the AA genotype and periodontal disease. No evident relationships were observed between SNP rs1800587 or rs1143634 and periodontal disease. Our study did not reveal any evidence of interaction between the IL1 polymorphisms and smoking. The results of this study showed that the heterozygous variant genotype of the IL1 rs16944 was significantly associated with a reduced risk of periodontal disease in young Japanese women. Smoking did not significantly modify the gene–disease associations under study.
doi:10.1089/dna.2013.2202
PMCID: PMC3967353  PMID: 24460370
4.  Calcium intake is associated with decreased prevalence of periodontal disease in young Japanese women 
Nutrition Journal  2014;13:109.
Background
We investigated the relationships between calcium intake and the prevalence of periodontal disease.
Methods
This cross-sectional study included 1162 women with a mean age of 31.5 years. Information on dietary factors was collected using a diet history questionnaire during pregnancy. Oral examinations were performed between one and twelve months postpartum. Periodontal disease was defined as positive if a woman had at least one tooth with a pocket depth of 4.0 mm or deeper. Adjustment was made for age, region of residence, smoking status, toothbrushing frequency, use of an interdental brush, household income, and education.
Results
Compared with the lowest quartile of calcium intake, the highest quartile was significantly associated with a lower prevalence of periodontal disease; however, the inverse linear trend fell just short of the significance level: the adjusted odds ratio was 0.53 (95% confidence interval: 0.30–0.94, P for trend =0.07).
Conclusions
Our findings suggest that higher calcium intake may be inversely associated with the prevalence of periodontal disease.
doi:10.1186/1475-2891-13-109
PMCID: PMC4251936  PMID: 25421835
Calcium; Cross-sectional studies; Periodontal disease; Women
5.  Relationship between Neural Rhythm Generation Disorders and Physical Disabilities in Parkinson’s Disease Patients’ Walking 
PLoS ONE  2014;9(11):e112952.
Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson’s disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients’ walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn–Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD.
doi:10.1371/journal.pone.0112952
PMCID: PMC4227866  PMID: 25386639
6.  The Effect of Visual Apparent Motion on Audiovisual Simultaneity 
PLoS ONE  2014;9(10):e110224.
Visual motion information from dynamic environments is important in multisensory temporal perception. However, it is unclear how visual motion information influences the integration of multisensory temporal perceptions. We investigated whether visual apparent motion affects audiovisual temporal perception. Visual apparent motion is a phenomenon in which two flashes presented in sequence in different positions are perceived as continuous motion. Across three experiments, participants performed temporal order judgment (TOJ) tasks. Experiment 1 was a TOJ task conducted in order to assess audiovisual simultaneity during perception of apparent motion. The results showed that the point of subjective simultaneity (PSS) was shifted toward a sound-lead stimulus, and the just noticeable difference (JND) was reduced compared with a normal TOJ task with a single flash. This indicates that visual apparent motion affects audiovisual simultaneity and improves temporal discrimination in audiovisual processing. Experiment 2 was a TOJ task conducted in order to remove the influence of the amount of flash stimulation from Experiment 1. The PSS and JND during perception of apparent motion were almost identical to those in Experiment 1, but differed from those for successive perception when long temporal intervals were included between two flashes without motion. This showed that the result obtained under the apparent motion condition was unaffected by the amount of flash stimulation. Because apparent motion was produced by a constant interval between two flashes, the results may be accounted for by specific prediction. In Experiment 3, we eliminated the influence of prediction by randomizing the intervals between the two flashes. However, the PSS and JND did not differ from those in Experiment 1. It became clear that the results obtained for the perception of visual apparent motion were not attributable to prediction. Our findings suggest that visual apparent motion changes temporal simultaneity perception and improves temporal discrimination in audiovisual processing.
doi:10.1371/journal.pone.0110224
PMCID: PMC4190322  PMID: 25295594
7.  Seaweed consumption and prevalence of depressive symptoms during pregnancy in Japan: Baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Background
Seaweed is a popular traditional food in Japan and is a rich source of bioactive metabolites. The neuroprotective properties of seaweed have attracted attention; to date, however, there has been no epidemiological evidence regarding the relationship between seaweed consumption and depression. The current cross-sectional study investigated the association between seaweed consumption and depressive symptoms during pregnancy in Japan.
Methods
Study subjects were 1745 pregnant women. Depressive symptoms were defined as present when subjects had a Center for Epidemiologic Studies Depression Scale score of 16 or higher. Dietary consumption during the preceding month was assessed using a self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of children; family structure; history of depression; family history of depression; smoking; secondhand smoke exposure at home and at work; job type; household income; education; body mass index; and intake of fish and yogurt.
Results
The prevalence of depressive symptoms during pregnancy was 19.3%. After adjustment for possible dietary and non-dietary confounding factors, higher seaweed consumption was independently associated with a lower prevalence of depressive symptoms during pregnancy: the adjusted odds ratios (95% confidence intervals) for depressive symptoms during pregnancy in the first, second, third, and fourth quartiles of seaweed consumption were 1 (reference), 0.72 (0.51 − 1.004), 0.71 (0.50 − 1.01), and 0.68 (0.47 − 0.96), respectively (P for trend = 0.03).
Conclusions
The present results suggest that seaweed consumption may be inversely associated with the prevalence of depressive symptoms during pregnancy in Japanese women.
doi:10.1186/1471-2393-14-301
PMCID: PMC4161851  PMID: 25186917
Cross-sectional study; Depressive symptoms; Intake; Japanese women; Pregnancy; Seaweed
8.  Interpersonal Similarity between Body Movements in Face-To-Face Communication in Daily Life 
PLoS ONE  2014;9(7):e102019.
Individuals are embedded in social networks in which they communicate with others in their daily lives. Because smooth face-to-face communication is the key to maintaining these networks, measuring the smoothness of such communication is an important issue. One indicator of smoothness is the similarity of the body movements of the two individuals concerned. A typical example noted in experimental environments is the interpersonal synchronization of body movements such as nods and gestures during smooth face-to-face communication. It should therefore be possible to estimate quantitatively the smoothness of face-to-face communication in social networks through measurement of the synchronization of body movements. However, this is difficult because social networks, which differ from disciplined experimental environments, are open environments for the face-to-face communication between two individuals. In such open environments, their body movements become complicated by various external factors and may follow unstable and nonuniform patterns. Nevertheless, we consider there to be some interaction during face-to-face communication that leads to the interpersonal synchronization of body movements, which can be seen through the interpersonal similarity of body movements. The present study aims to clarify such interaction in terms of body movements during daily face-to-face communication in real organizations of more than 100 people. We analyzed data on the frequency of body movement for each individual during face-to-face communication, as measured by a wearable sensor, and evaluated the degree of interpersonal similarity of body movements between two individuals as their frequency difference. Furthermore, we generated uncorrelated data by resampling the data gathered and compared these two data sets statistically to distinguish the effects of actual face-to-face communication from those of the activities accompanying the communication. Our results confirm an interpersonal similarity of body movements between two individuals in face-to-face communication, for all the organizations studied, and suggest that some body interaction is behind this similarity.
doi:10.1371/journal.pone.0102019
PMCID: PMC4094526  PMID: 25014021
9.  Low birth weight, preterm birth or small-for-gestational-age are not associated with dental caries in young Japanese children 
BMC Oral Health  2014;14:38.
Background
Low birth weight (LBW) continues to increase and is a major public health problem in Japan. In the present cross-sectional study, we examined the associations between LBW, preterm birth and small-for-gestational-age (SGA) and the prevalence of dental caries in young Japanese children.
Methods
Study subjects were 2,055 children aged 3 years. Data on birth conditions were obtained through the transcription by parents or guardians of the information from their maternal and child health handbook, in which the data were recorded by staff at the birth hospital or clinic, to our self-administered questionnaire. Children were classified as having caries if one or more deciduous teeth were decayed, missing, or had been filled at the time of examination. Adjustments were made for sex, toothbrushing frequency, use of fluoride, regular dental check-ups, between-meal snack frequency, breastfeeding duration, paternal and maternal educational levels, maternal smoking during pregnancy, and secondhand smoke exposure at home.
Results
The prevalence of dental caries was 20.7%. The mean birth weight was 3018.3 g, and 8.3% were classified as LBW (<2,500 g), 4.5% as preterm birth (<37 weeks), and 7.1% as SGA (<10th percentile). Preterm birth was associated with a 40% decreased prevalence of dental caries (adjusted prevalence ratio = 0.60, 95% confidence interval: 0.36–1.02, p = 0.06). There were no associations between LBW or SGA and the prevalence of dental caries.
Conclusions
The results of the study failed to detect significant associations between LBW, preterm birth or SGA and the prevalence of dental caries in Japan. Further study is needed in other populations to confirm the generalizability of these findings.
doi:10.1186/1472-6831-14-38
PMCID: PMC3989784  PMID: 24731399
Child; Dental caries; Japan; Low birth weight; Preterm birth; Small-for-gestational-age
10.  Alcohol consumption during pregnancy and birth outcomes: the Kyushu Okinawa Maternal and Child Health Study 
Background
A recent meta-analysis showed no relationships between light to moderate alcohol consumption during pregnancy and the risk of low birth weight (LBW), preterm birth (PTB), or small-for-gestational-age (SGA). Here, we present the first epidemiological study on this topic in Japan.
Methods
Study subjects were 1565 Japanese mothers with singleton pregnancies and the babies born from these pregnancies. Alcohol consumption during pregnancy was assessed using a self-administered diet history questionnaire. Alcohol consumption during pregnancy was classified into three categories (none, < 1 g/day, and ≥ 1 g/day).
Results
The mean birth weight of the babies was 3006.3 g. 7.7% were classified as LBW, 4.0% as PTB, and 7.8% as SGA. The range of maternal alcohol consumption during pregnancy was 0.0 to 11.7 g per day: 1356 (86.7%) mothers were abstainers and the 95th percentile value was 0.84 g per day. Compared with abstinence, alcohol consumption of 1.0 g or more per day during pregnancy was significantly associated with an increased risk of PTB with a significant positive linear trend: the adjusted OR for PTB associated with maternal alcohol consumption of 1.0 g or more per day was 2.58 (95% CI: 1.004 - 5.80, P for trend = 0.03). No significant relationships were observed between maternal alcohol consumption during pregnancy and the risk of LBW or SGA, and there was no material association between maternal alcohol consumption during pregnancy and birth weight.
Conclusions
This is the first study in Japan to show that maternal alcohol consumption during pregnancy of 1.0 g or more per day was significantly positively associated with the risk of PTB, but not LBW or SGA.
doi:10.1186/1471-2393-14-79
PMCID: PMC3933512  PMID: 24555868
11.  Interactive Rhythmic Cue Facilitates Gait Relearning in Patients with Parkinson's Disease 
PLoS ONE  2013;8(9):e72176.
To develop a method for cooperative human gait training, we investigated whether interactive rhythmic cues could improve the gait performance of Parkinson's disease patients. The interactive rhythmic cues ware generated based on the mutual entrainment between the patient's gait rhythms and the cue rhythms input to the patient while the patient walked. Previously, we found that the dynamic characteristics of stride interval fluctuation in Parkinson's disease patients were improved to a healthy 1/f fluctuation level using interactive rhythmic cues and that this effect was maintained in the short term. However, two problems remained in our previous study. First, it was not clear whether the key factor underpinning the effect was the mutual entrainment between the gait rhythms and the cue rhythms or the rhythmic cue fluctuation itself. Second, it was not clear whether or not the gait restoration was maintained longitudinally and was relearned after repeating the cue-based gait training. Thus, the present study clarified these issues using 32 patients who participated in a four-day experimental program. The patients were assigned randomly to one of four experimental groups with the following rhythmic cues: (a) interactive rhythmic cue, (b) fixed tempo cue, (c) 1/f fluctuating tempo cue, and (d) no cue. It has been reported that the 1/f fluctuation of stride interval in healthy gait is absent in Parkinson's disease patients. Therefore, we used this dynamic characteristic as an evaluation index to analyze gait relearning in the four different conditions. We observed a significant effect in condition (a) that the gait fluctuation of the patients gradually returned to a healthy 1/f fluctuation level, whereas this did not occur in the other conditions. This result suggests that the mutual entrainment can facilitate gait relearning effectively. It is expected that interactive rhythmic cues will be widely applicable in the fields of rehabilitation and assistive technology.
doi:10.1371/journal.pone.0072176
PMCID: PMC3787045  PMID: 24098631
12.  Active and passive maternal smoking during pregnancy and birth outcomes: the Kyushu Okinawa Maternal and Child Health Study 
Background
In Western countries, active maternal smoking during pregnancy is recognized as the most important preventable risk factor for adverse birth outcomes. However, the effect of passive maternal smoking is less clear and has not been extensively studied. In Japan, there has been only one epidemiological study which examined the effects of active smoking during early pregnancy on birth outcomes although the effects of passive smoking were not assessed.
Methods
Study subjects were 1565 mothers with singleton pregnancies and the babies born from these pregnancies. Data on active maternal smoking status in the first, second, and third trimesters and maternal environmental tobacco smoke (ETS) exposure at home and work were collected with self-administered questionnaires.
Results
Compared with children born to mothers who had never smoked during pregnancy, children born to mothers who had smoked throughout their pregnancy had a significantly increased risk of small-for-gestational-age (SGA) (adjusted odd ratio [OR] = 2.87; 95% confidence interval: 1.11 − 6.56). However, active maternal smoking only in the first trimester and active maternal smoking in the second and/or third trimesters but not throughout pregnancy were not significantly associated with SGA. With regard to the risk of preterm birth, the adjusted ORs for the above-mentioned three categories were not significant; however, the positive linear trend was significant (P for trend = 0.048). No significant association was found between active maternal smoking during pregnancy and the risk of low birth weight. There was a significant inverse relationship between active maternal smoking during pregnancy and birth weight; newborns of mothers who had smoked throughout pregnancy had an adjusted mean birth weight reduction of 169.6 g. When classifying babies by gender, a significant positive association between active maternal smoking throughout pregnancy and the risk of SGA was found only in male newborns, however, the interaction was not significant. Maternal ETS exposure at home or work was not significantly associated with any birth outcomes.
Conclusions
This is the first study in Japan to show that active maternal smoking throughout pregnancy, but not during the first trimester, is significantly associated with an increased risk of SGA and a decrease in birth weight. Thus, women who smoke should quit smoking as soon as possible after conception.
doi:10.1186/1471-2393-13-157
PMCID: PMC3750375  PMID: 23919433
13.  Interactive cueing with walk-Mate for Hemiparetic Stroke Rehabilitation 
Background
Many techniques that compensate for locomotion problems in daily life using externally controlled stimulation have recently been reported. These techniques are beneficial for effortlessly supporting patients’ locomotive functions, but the users of such devices must necessarily remain dependent on them. It is possible that some individuals with gait impairment may be prevented recovering locomotive function. From a rehabilitation viewpoint, it may therefore be supposed that ideally, devices that can be used in daily life to improve the locomotive functions of the body itself should be proposed.
Methods
We evaluate the effectiveness of Walk-Mate, which has been used mainly as a gait compensation device, as a gait rehabilitation training device by analyzing improvement in locomotion before, during and after rehabilitation in hemiparetic patients and comparing it with a previous gait training method. Walk-Mate generates a model walking rhythm in response to a user’s locomotion in real time, and by indicating this rhythm using auditory stimuli, provides a technology that supports walking by reducing asymmetries and fluctuations in foot contact rhythm. If patients can use the system to learn a regulated walking rhythm, then it may also be expected to fulfil the functions of a gait rehabilitation training device for daily life.
Results
With regard to asymmetry, significantly improvements were seen for compensatory movement during training using Walk-Mate, but improvements were not retained as rehabilitative results. Regarding fluctuations in the foot contact period, significant improvement was observed for compensatory movement during training and these significant improvements were retained as rehabilitative results. In addition, it became clear that such improvement could not be adequately obtained by the previously proposed training technique utilizing constant rhythmic auditory stimulation.
Conclusions
Walk-Mate effectively compensated for locomotion problems of hemiparetic patients by improving gait rhythm both during and after training, suggesting that locomotive function can be effectively recovered in some patients. The interactive mechanism of Walk-Mate may be capable of simultaneously achieving the aims of gait compensation and gait rehabilitation training methods previously developed under individual frameworks. Walk-Mate is a promising technology for assisting the reintegration of disabled persons into society.
doi:10.1186/1743-0003-9-58
PMCID: PMC3480930  PMID: 22909032
14.  Employment, income, and education and prevalence of depressive symptoms during pregnancy: the Kyushu Okinawa Maternal and Child Health Study 
BMC Psychiatry  2012;12:117.
Background
Epidemiological evidence for the association of socioeconomic status with prenatal depression has been inconsistent. The current cross-sectional study examined the association between employment, job type, household income, and educational level and the prevalence of depressive symptoms during pregnancy.
Methods
Subjects were 1741 Japanese women. Depressive symptoms were defined as present when subjects had a Center for Epidemiologic Studies Depression Scale score of 16 or higher. Adjustment was made for age, gestation, region of residence, family structure, personal and family history of depression, smoking, secondhand smoke exposure at home and at work, employment, household income, and education.
Results
The prevalence of depressive symptoms during pregnancy was 19.3%. Compared with unemployment, employment, part-time employment, and full-time employment were significantly associated with a lower prevalence of depressive symptoms during pregnancy: the adjusted odds ratios (ORs) were 0.65 (95% confidence interval [CI]: 0.50 − 0.86), 0.66 (95% CI: 0.46 − 0.95), and 0.66 (95% CI: 0.48 − 0.90), respectively. Regarding the job type held, women with a professional or technical job and those with a clerical or related occupation had a significantly lower prevalence of depressive symptoms during pregnancy: the adjusted ORs were 0.67 (95% CI: 0.47 − 0.96) and 0.62 (95% CI: 0.43 − 0.90), respectively. Sales, service, production, and other occupations were not significantly related to the prevalence of depressive symptoms during pregnancy. There were no relationships between household income or education and the prevalence of depressive symptoms during pregnancy.
Conclusions
Employment, whether full-time or part-time, and holding a professional or technical job or a clerical or related occupation may be inversely associated with the prevalence of depressive symptoms during pregnancy.
doi:10.1186/1471-244X-12-117
PMCID: PMC3503653  PMID: 22900835
Cross-sectional study; Depressive symptoms during pregnancy; Education; Employment; Income; Japanese
15.  UCHL1 S18Y variant is a risk factor for Parkinson’s disease in Japan 
BMC Neurology  2012;12:62.
Background
A recent meta-analysis on the UCHL1 S18Y variant and Parkinson’s disease (PD) showed a significant inverse association between the Y allele and PD; the individual studies included in that meta-analysis, however, have produced conflicting results. We examined the relationship between UCHL1 S18Y single nucleotide polymorphism (SNP) and sporadic PD in Japan.
Methods
Included were 229 cases within 6 years of onset of PD, defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, smoking, and caffeine intake.
Results
Compared with subjects with the CC or CA genotype of UCHL1 S18Y SNP, those with the AA genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95 % CI: 1.06 − 2.31). Compared with subjects with the CC or CA genotype of UCHL1 S18Y and the CC or CT genotype of SNCA SNP rs356220, those with the AA genotype of UCHL1 S18Y and the TT genotype of SNP rs356220 had a significantly increased risk of sporadic PD; the interaction, however, was not significant. Our previous investigation found significant inverse relationships between smoking and caffeine intake and PD in this population. There were no significant interactions between UCHL1 S18Y and smoking or caffeine intake affecting sporadic PD.
Conclusions
This study reveals that the UCHL1 S18Y variant is a risk factor for sporadic PD. We could not find evidence for interactions affecting sporadic PD between UCHL1 S18Y and SNCA SNP rs356220, smoking, or caffeine intake.
doi:10.1186/1471-2377-12-62
PMCID: PMC3488468  PMID: 22839974
16.  Dairy products and calcium intake during pregnancy and dental caries in children 
Nutrition Journal  2012;11:33.
Background
Maternal nutrition status during pregnancy may affect fetal tooth development, formation, and mineralization, and may affect dental caries susceptibility in children. We investigated the association between maternal intake of dairy products and calcium during pregnancy and the risk of childhood dental caries.
Methods
Subjects were 315 Japanese mother-child pairs. Data on maternal intake during pregnancy were assessed through a diet history questionnaire. Outcome data was collected at 41–50 months of age. Children were classified as having dental caries if one or more primary teeth had decayed or been filled.
Results
Higher maternal cheese intake during pregnancy was significantly inversely associated with the risk of dental caries in children, showing a clear inverse dose–response relationship; the adjusted odds ratio (OR) in comparison of the highest tertile with the lowest was 0.37 (95 % confidence interval [CI]: 0.17-0.76, P for trend = 0.01). The inverse associations between maternal intake of total dairy products, yogurt, and calcium during pregnancy and the risk of childhood dental caries were of borderline significance: the adjusted ORs for the highest tertile of total dairy products, yogurt, and calcium were 0.51 (95 % CI: 0.23-1.09, P for trend = 0.07), 0.51 (95 % CI: 0.23-1.10, P for trend = 0.07), and 0.50 (95 % CI: 0.23-1.07, P for trend = 0.08), respectively. There was no evident relationship between maternal milk intake and the risk of childhood dental caries.
Conclusion
These data suggested that high intake of maternal cheese during pregnancy may reduce the risk of childhood dental caries.
doi:10.1186/1475-2891-11-33
PMCID: PMC3411471  PMID: 22594463
Calcium; Dairy products; Dental caries; Prospective study
17.  Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Nutrition Journal  2012;11:19.
Background
Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan.
Methods
Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index.
Results
The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis.
Conclusions
The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.
doi:10.1186/1475-2891-11-19
PMCID: PMC3342884  PMID: 22449171
18.  Smoking and prevalence of allergic disorders in Japanese pregnant women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Environmental Health  2012;11:15.
Background
Studies on the associations between smoking and allergic diseases have mostly focused on asthma. Epidemiological studies in adults on the effects of smoking on allergic diseases other than asthma, such as eczema and rhinoconjunctivitis, have been limited, and the information that is available has been inconsistent. The aim of this study was to investigate the association between smoking status and environmental tobacco smoke (ETS) exposure and the prevalence of allergic diseases.
Methods
Study subjects were 1743 pregnant Japanese women. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age; region of residence; family history of asthma, atopic eczema, and allergic rhinitis; household income; and education.
Results
Compared with never smoking, current smoking and ≥ 4 pack-years of smoking were independently positively associated with the prevalence of wheeze. There were no associations between smoking status and the prevalence of asthma, eczema, or rhinoconjunctivitis. When subjects who had never smoked were classified into four categories based on the source of ETS exposure (never, only at home, only at work, and both), exposure occurring both at home and at work was independently associated with an increased prevalence of two outcomes: wheeze and rhinoconjunctivitis. No relationships were observed between exposure to ETS and the prevalence of asthma or eczema.
Conclusions
Our results provide evidence that current smoking and ETS exposure may increase the likelihood of wheeze. The possibility of a positive association between ETS exposure and rhinoconjunctivitis was also suggested.
doi:10.1186/1476-069X-11-15
PMCID: PMC3317840  PMID: 22413964
Asthma; Cross-sectional studies; Eczema; Environmental tobacco smoke; Smoking; Wheeze; Rhinoconjunctivitis
19.  Interactive Rhythmic Auditory Stimulation Reinstates Natural 1/f Timing in Gait of Parkinson's Patients 
PLoS ONE  2012;7(3):e32600.
Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times—rather than the 1/f structure observed in healthy gait—and this randomness of stride times (low fractal scaling) predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure) and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a) no auditory stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (re)emergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients.
doi:10.1371/journal.pone.0032600
PMCID: PMC3292577  PMID: 22396783
20.  Association Between Breastfeeding and Dental Caries in Japanese Children 
Journal of Epidemiology  2012;22(1):72-77.
Background
Studies investigating the impact of breastfeeding on dental caries have produced contradictory results. This cross-sectional study investigated the relationship between breastfeeding and the prevalence of dental caries in young Japanese children.
Methods
The study subjects were 2056 Japanese children aged 3 years. Information on breastfeeding was obtained by means of a questionnaire. Children were classified as having caries if 1 or more deciduous teeth were decayed, missing, or had been filled at the time of examination.
Results
The prevalence of dental caries was 20.7%. As compared with breastfeeding for less than 6 months, breastfeeding for 18 months or longer was associated with a significantly higher prevalence of dental caries. The relation was J-shaped: the adjusted prevalence ratios for less than 6 months, 6 to 11 months, 12 to 17 months, and 18 months or longer were 1.0, 0.79 (95% confidence interval [CI]: 0.60–1.05), 0.86 (95% CI: 0.66–1.13), and 1.66 (95% CI: 1.33–2.06), respectively (P for linear trend <0.0001, P for quadratic trend <0.0001).
Conclusions
Breastfeeding for 18 months or longer was positively associated with the prevalence of dental caries, while breastfeeding for 6 to 17 months was nonsignificantly inversely associated with the prevalence of dental caries.
doi:10.2188/jea.JE20110042
PMCID: PMC3798583  PMID: 22156287
breastfeeding; cross-sectional studies; dental caries; Japan
21.  Case-control study of IL13 polymorphisms, smoking, and rhinoconjunctivitis in Japanese women: the Kyushu Okinawa Maternal and Child Health Study 
BMC Medical Genetics  2011;12:143.
Background
Six previous studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the IL13 gene and allergic rhinitis, but the results have been inconsistent. However, a recent meta-analysis using data from these 6 studies has shown that the A allele of IL13 SNP rs20541 was associated with an increased risk of allergic rhinitis, whereas no such relationship existed between IL13 SNP rs1800925 and allergic rhinitis. We investigated the associations between IL13 SNPs rs1800925 and rs20541 and the risk of rhinoconjunctivitis in Japanese women.
Methods
Included were 393 cases who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Control subjects were 767 women without rhinoconjunctivitis according to the ISAAC criteria, who had also not been diagnosed with allergic rhinitis by a doctor. Adjustment was made for age, region of residence, presence of older siblings, smoking, family history of allergic rhinitis, and education.
Results
Compared with the GG genotype of IL13 SNP rs20541, the AA genotype, occurring in 7.1% of control subjects, was significantly positively related to the risk of rhinoconjunctivitis: the adjusted odds ratio was 1.65 (95% confidence interval: 1.05 - 2.60). SNP rs1800925 was not associated with rhinoconjunctivitis. The haplotype comprising the rs1800925 C allele and the rs20541 A allele was significantly positively related to rhinoconjunctivitis. The multiplicative interactions between the two SNPs under study and smoking on the risk of rhinoconjunctivitis were not statistically significant. Based on the recessive model, however, the additive interaction between SNP rs1800925, but not rs20541, and smoking was significant.
Conclusions
This study suggests that the minor genotype of IL13 SNP rs20541 and the CA haplotype are significantly positively associated with the risk of rhinoconjunctivitis. In addition, a new pattern of biological interaction that affects the risk of rhinoconjunctivitis is described between SNP rs1800925 and smoking.
doi:10.1186/1471-2350-12-143
PMCID: PMC3214177  PMID: 22023794
22.  IL13 genetic polymorphisms, smoking, and eczema in women: a case-control study in Japan 
BMC Medical Genetics  2011;12:142.
Background
Several genetic association studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the IL13 gene and eczema, and have provided contradictory results. We investigated the relationship between the IL13 SNPs rs1800925 and rs20541 and the risk of eczema in Japanese young adult women.
Methods
Included were 188 cases who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for eczema. Control subjects were 1,082 women without eczema according to the ISAAC criteria, who had not been diagnosed with atopic eczema by a doctor and who had no current asthma as defined by the European Community Respiratory Health Survey criteria. Adjustment was made for age, region of residence, number of children, smoking, and education.
Results
The minor TT genotype of SNP rs1800925 was significantly associated with an increased risk of eczema in the co-dominant model: the adjusted odds ratio was 2.19 (95% confidence interval: 1.03-4.67). SNP rs20541 was not related to eczema. None of the haplotypes were significantly associated with eczema. Compared with women with the CC or CT genotype of SNP rs1800925 who had never smoked, those with the TT genotype who had ever smoked had a 2.85-fold increased risk of eczema, though the adjusted odds ratio was not statistically significant, and neither multiplicative nor additive interaction was statistically significant.
Conclusions
Our findings suggest that the IL13 SNP rs1800925 is significantly associated with eczema in Japanese young adult women. We could not find evidence for an interaction between SNP rs1800925 and smoking with regard to eczema.
doi:10.1186/1471-2350-12-142
PMCID: PMC3206833  PMID: 22013915
23.  Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population 
BMC Neurology  2011;11:89.
Background
Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD.
Methods
We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population.
Results
Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed.
Conclusions
The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.
doi:10.1186/1471-2377-11-89
PMCID: PMC3199768  PMID: 21781348
24.  Sibling number and prevalence of allergic disorders in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
BMC Public Health  2011;11:561.
Background
Although an inverse relationship between number of siblings and likelihood of allergic disorders has been shown in many epidemiological studies, the biological mechanism underlying this phenomenon has not yet been identified. There is no epidemiological research regarding the sibling effect on allergic disorders in Japanese adults. The current cross-sectional study examined the relationship between number of siblings and prevalence of allergic disorders among adult women in Japan.
Methods
Subjects were 1745 pregnant women. This study was based on questionnaire data. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age, region of residence, pack-years of smoking, secondhand smoke exposure at home and at work, family history of asthma, atopic eczema, and allergic rhinitis, household income, and education.
Results
The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the past 12 months were 10.4%, 5.5%, 13.0%, and 25.9%, respectively. A significant inverse exposure-response relationship was observed between the number of older siblings and rhinoconjunctivitis, but not wheeze, asthma, or eczema (P for trend = 0.03); however, the adjusted odds ratio (OR) for having 2 or more older siblings was not significant although the adjusted OR for having 1 older sibling was statistically significant (adjusted OR = 0.71 [95% CI: 0.56-0.91]). Number of total siblings and number of younger siblings were not related to wheeze, asthma, eczema, or rhinoconjunctivitis.
Conclusions
This study found a significant inverse relationship between the number of older siblings and the prevalence of rhinoconjunctivitis among pregnant Japanese women. Our findings are likely to support the intrauterine programming hypothesis; however, we could not rule out the hygiene hypothesis.
doi:10.1186/1471-2458-11-561
PMCID: PMC3142516  PMID: 21752304
25.  Occupational risk factors for Parkinson's disease: a case-control study in Japan 
BMC Neurology  2011;11:83.
Background
The evidence for associations between occupational factors and the risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD associated with various occupational factors in Japan.
Methods
We examined 249 cases within 6 years of onset of PD. Control subjects were 369 inpatients and outpatients without neurodegenerative disease. Information on occupational factors was obtained from a self-administered questionnaire. Relative risks of PD were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based on logistic regression. Adjustments were made for gender, age, region of residence, educational level, and pack-years of smoking.
Results
Working in a professional or technical occupation tended to be inversely related to the risk of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, P = 0.08). According to a stratified analysis by gender, the decreased risk of PD for persons in professional or technical occupations was statistically significant only for men. Adjusted ORs for a professional or technical occupation among men and women were 0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant interaction was observed (P = 0.048 for homogeneity of OR). In contrast, risk estimates for protective service occupations and transport or communications were increased, although the results were not statistically significant: adjusted ORs were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No statistical significance was seen in data concerning exposure to occupational agents and the risk of PD, although roughly a 2-fold increase in OR was observed for workers exposed to stone or sand.
Conclusion
The results of our study suggest that occupational factors do not play a substantial etiologic role in this population. However, among men, professional or technical occupations may decrease the risk of PD.
doi:10.1186/1471-2377-11-83
PMCID: PMC3171313  PMID: 21733194

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