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Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social, or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analyzed GWAS data on sweets consumption using 14,073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with sweets consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1 to 3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/day) in addition to the above-described variables. We found 418 single nucleotide polymorphisms (SNPs) located in 12q24 that were associated with sweets consumption. SNPs with the 10 lowest P-values were located on nine genes including at the BRAP, ACAD10, and ALDH2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with sweets intake with genome-wide significance. In conclusion, we found a significant number of SNPs located on 12q24 genes that were associated with sweets intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.
The current study aimed to predict disability-adjusted life years (DALY) rate in Japan through 2040 with plausible future scenarios of fruit intake for neoplasms, cardiovascular diseases (CVD) and diabetes and kidney diseases (DKD).
Data from National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017 were used. We developed an autoregressive integrated moving average model with four future scenarios. Reference scenario maintains the current trend. Best scenario assumes that the goal defined in Health Japan 21 is achieved in 2023 and is kept constant afterwards. Moderate scenario assumes that the goal is achieved in 2040. Constant scenario applies the same proportion of 2016 for the period between 2017 and 2040.
DALY rates in Japan were predicted for the period between 2017 and 2040.
Population aged more than than 20 years old.
In our reference forecast, the DALY rates in all-ages group were projected to be stable for CVD and continue increasing for neoplasms and DKD. Age group-specific DALY rates for these three disease groups were forecasted to decrease, with some exceptions. Among men aged 20–49 years, DALY attributable to CVD differed substantially between the scenarios, implying that there is a significant potential for reducing the burden of CVD by increasing fruit intake at the population level.
Our scenario analysis shows that higher fruit intake is associated with lower disease burden in Japan. Further research is required to assess which policies and interventions can be used to achieve an increase in fruit intake as modelled in the scenarios of the current study.
Gestational nutrition is widely recognized to affect an offspring’s future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(−)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(−) than FA(+) dams. Notably, in the skin of FA(−) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(−) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, “innate” utero nutrition as the third cause of tumorigenesis besides the known causes—hereditary predisposition and acquired environmental factors.
Collusion is a largely unconscious, dynamic bond, which may occur between patients and clinicians, between patients and family members, or between different health professionals. It is widely prevalent in the palliative care setting and provokes intense emotions, unreflective behavior, and negative impact on care. However, research on collusion is limited due to a lack of conceptual clarity and robust instruments to investigate this complex phenomenon. We have therefore developed the Collusion Classification Grid (CCG), which we aimed to evaluate with regard to its potential utility to analyze instances of collusion, be it for the purpose of supervision in the clinical setting or research.
Situations of difficult interactions with patients with advanced disease (N = 10), presented by clinicians in supervision with a liaison psychiatrist were retrospectively analyzed by means of the CCG.
1) All items constituting the grid were mobilized at least once; 2) one new item had to be added; and 3) the CCG identified different types of collusion.
Significance of results
This case series of collusions assessed with the CCG is a first step before the investigation of larger samples with the CCG. Such studies could search and identify setting-dependent and recurrent types of collusions, and patterns emerging between the items of the CCG. A better grasp of collusion could ultimately lead to a better understanding of the impact of collusion on the patient encounter and clinical decision-making.
Few studies have reported the association between the Japanese diet as food score and mortality. This study aimed to investigate adherence to the Japanese food score associated with all-cause, CVD and cancer mortality. A total of 58 767 (23 162 men and 34 232 women) Japanese participants aged 40–79 years, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990, were included. The Japanese food score was derived from the components of seven food groups (beans and bean products, fresh fishes, vegetables, Japanese pickles, fungi, seaweeds and fruits) based on the FFQ. The total score ranged from 0 to 7, and participants were divided into five categories based on scores (0–2, 3, 4, 5 and 6–7). Hazard ratios (HR) and 95 % CI for all-cause, CVD and cancer mortality based on sex were estimated using Cox proportional models. During the follow-up period until 2009, 11 692 participants with all-cause, 3408 with CVD and 4247 with cancer died. The multivariable HR in the 6–7 and 0–2 Japanese food score groups were 0·93 (95 % CI 0·86, 1·01) in men and 0·82 (95 % CI 0·75, 0·90) in women for all-cause mortality and 0·89 (95 % CI 0·76, 1·04) in men and 0·66 (95 % CI 0·56, 0·77) in women for CVD mortality. Our findings suggest that adherence to the Japanese food score consisting of food combinations characterised by a Japanese diet may help in preventing all-cause and CVD mortality, especially in women.
Higher daytime cortisol levels because of a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts.
To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method.
The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement.
Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected).
Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal–subcortical and frontal–limbic circuits.
The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining.
The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95).
Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level.
J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function.
Background: The aim of this study was to identify the neural correlates of each component of the clock drawing test (CDT) in drug-naïve patients with Alzheimer's disease (AD) using single photon emission computed tomography.
Methods: The participants were 95 drug-naïve patients with AD. The Rouleau CDT was used to score the clock drawings. The score for the Rouleau CDT (R total) is separated into three components: the scores for the clock face (R1), the numbers (R2), and the hands (R3). A multiple regression analysis was performed to examine the relationship of each score (i.e. R total, R1, R2, and R3) with regional cerebral blood flow (rCBF). Age, gender, and education were included as covariates. The statistical threshold was set to a family-wise error (FWE)-corrected p value of 0.05 at the voxel level.
Results: The R total score was positively correlated with rCBF in the bilateral parietal and posterior temporal lobes and the right middle frontal gyrus. R1 was not significantly positively correlated with rCBF, R2 was significantly positively correlated with rCBF in the right posterior temporal lobe and the left posterior middle temporal lobe, and R3 was significantly positively correlated with rCBF in the bilateral parietal lobes, the right posterior temporal lobe, the right middle frontal gyrus, and the right occipital lobe.
Conclusions: Various brain regions were associated with each component of the CDT. These results suggest that an assessment of these components is useful for the detection of localization of brain damage.
We developed a portable ozone-mist sterilization system to exterminate pests (harmful insects) in agricultural field and greenhouse. The system is composed of an ozone generator, an ozone-mist spray and a small container of ozone gas. The ozone generator can supply highly concentrated ozone using the surface dielectric barrier discharge. Ozone-mist is produced using a developed nozzle system. We studied the effects of ozone-mist spray sterilization on insects and agricultural plants. The sterilization conditions are estimated by monitoring the behavior of aphids and observing the damage of the plants. It was shown that aphids were exterminated in 30 s without noticeable damages of the plant leaves. The reactive radicals with strong oxidation potential such as hydroxyl radical (*OH), hydroperoxide radical (*HO2), the superoxide ion radical (*O2‒) and ozonide radical ion (*O3‒) can increase the sterilization rate for aphids.
We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients.
Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively.
Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG).
The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels.
Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.
A thin metal film with nano-apertures, called “nano-mesh electrode,” generates near-field lights near the electrode. We investigated carrier excitations in semiconductors by the near-field light. Finite-difference time-domain (FDTD) method revealed that when the infrared light irradiates the Au nano-mesh electrode on Ge, near-field lights are generated and absorbed in the surface region of the Ge. In order to measure the photocurrent involved by near-filed lights, we fabricated a Schottky cell and applied a Au nano-mesh electrode on the n-type Ge. The efficiency of the Schottky cell with the Au nano-mesh electrode improved in infrared region compared to plain the Au-film Schottky cell. The agreement between theoretical simulations and experiments indicates that near-field lights enhance the carrier excitation in the semiconductor.
The three-dimensional structure of crack tip dislocations in single crystal silicon was observed by combining high-voltage electron microscopy and tomography. It was revealed that dislocations cross-slipped proximal to the crack tip even in the initial stages of plastic deformation. The local stress intensity factor along the crack front was calculated by taking into account the experimentally determined dislocation character. Based on these observations and calculations, a model to account for the sequential multiplication of dislocation sources along the crack front is proposed.
We investigated whether the small litter size in the 129 inbred mouse strain results from a reduction in oocyte fertilizability. Sensitivity of the zona pellucida to α-chymotrypsin was examined for oocytes collected at 14 h (shortly after ovulation), 17 h, and 20 h after hCG injection. Passage of spermatozoa through the zona pellucida (using an in vitro fertilization (IVF) technique) and the density of cortical granules were examined for oocytes collected at 14 and 17 h after hCG injection. The capability of the oolemma to fuse with the sperm plasma membrane was also evaluated by IVF using zona-free eggs. The zona pellucida became markedly resistant to the enzyme 17 h after hCG injection. IVF rates significantly decreased at this time. In addition, there was a significant reduction in the density of cortical granules. When zona-free oocytes were inseminated, high fertilization rates were obtained at both 17 and 14 h after hCG injection. These results indicate that accelerated modification of the zona pellucida primarily causes a decreased fertilizability of oocytes in 129 mice, resulting in the low reproductive performance of this strain.
The aim of the present study was to investigate metabolite alterations in the hippocampal formation as they relate to aggression in high-functioning adults with autism. We measured concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr+PCr) in the hippocampal formation by proton magnetic resonance spectroscopy in 12 non-medicated male subjects with autism and 12 age- and sex-matched controls. Aggression was scored in the autistic subjects using the Buss–Perry Aggression Questionnaire. The concentrations of Cho and Cr+PCr in the hippocampal formation in autistic subjects were significantly higher than the corresponding values in control subjects, and a significant positive correlation was observed between the concentrations of these metabolites in the hippocampal formation and scores on the Buss–Perry Aggression Questionnaire in autistic subjects. Results suggest that high-functioning adult subjects with autism have abnormal metabolite concentrations in the hippocampal formation, which may in part account for their aggression.
The open-system pingos of Spitsbergen are formed outside terminal moraines, fault zones, and delta areas. Pingos in this study area were located near the shore in active geologic uplift areas. Three open-system pingos in the Adventdalen delta area of Spitsbergen were examined. Pingos closer to shore are younger in age and those farther away are older. Growth of these pingos occurs rapidly after initial submarine uplift and a minimum thickness of permafrost is established. Hut pingo, which is farthest from the sea, was formed after 6980±70 a BP (NUTA-3856). Driftwood associated with Longyear pingo, in the middle part of the delta, was dated at 2800±90 a BP. The radiocarbon age of peat near the shore pingo, Lagoon pingo, was 140±20 a BP. The growth of the pingos is related to transgression and development of permafrost.
The effectiveness and safety of yokukansan (TJ-54), a traditional Japanese medicine (kampo) for the treatment of the behavioural and psychological symptoms of dementia (BPSD), were evaluated in 106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. Patients were randomly assigned to group A (TJ-54 treatment in period I and no treatment in period II; each period lasting 4 wk) or group B (no treatment in period I and TJ-54 treatment in period II). BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. The effects of TJ-54 persisted for 1 month without any psychological withdrawal symptoms in group A. TJ-54 did not show any effect on either cognitive function or ADL. No serious adverse reactions were observed. The present study suggests that TJ-54 is an effective and well-tolerated treatment for patients with BPSD.
Previous studies have reported the association between advanced paternal
age at birth and the risk of autistic-spectrum disorder in offspring,
including offspring with intellectual disability.
To test whether an association between advanced paternal age at birth is
found in offspring with high-functioning autistic-spectrum disorder (i.e.
offspring without intellectual disability).
A case–control study was conducted in Japan. The participants consisted
of individuals with full-scale IQ ⩾ 70, with a DSM–IV autistic disorder
or related diagnosis. Unrelated healthy volunteers were recruited as
controls. Parental ages were divided into tertiles (i.e. three age
classes). Odds ratios and 95% confidence intervals were estimated using
logistic regression analyses, with an adjustment for age, gender and
Eighty-four individuals with autistic-spectrum disorder but without
intellectual disability and 208 healthy controls were enrolled. Increased
paternal, but not maternal, age was associated with an elevated risk of
high-functioning autistic-spectrum disorder. A one-level advance in
paternal age class corresponded to a 1.8-fold increase in risk, after
adjustment for covariates.
Advanced paternal age is associated with an increased risk for
high-functioning autistic-spectrum disorder.
Immune dysfunction has been proposed as a mechanism for the pathophysiology
of autistic-spectrum disorders. The selectin family of adhesion molecules
plays a prominent role in immune/inflammatory responses. We determined the
serum levels of three types of soluble-form selectin (sP, sL and sE) in 15
men with high-functioning autism and 22 age-matched healthy controls by
enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin
were significantly lower in patients than in controls. Furthermore,
sP-selectin levels were negatively correlated with impaired social
development during early childhood.
Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (5-HTT), which modulates serotonin levels, is a major therapeutic target in autism. Therefore, factors that regulate 5-HTT expression might be implicated in autism. One candidate 5-HTT-regulatory protein is the presynaptic protein, syntaxin 1A (STX1A). We examined the association of STX1A with autism in a trio association study using DNA samples from 249 AGRE trios with autistic probands. Only male probands were selected, since autism is more prevalent among males. The probands of 102 trios had IQ>70, and were considered as high functioning autism (HFA). In transmission disequilibrium test (TDT) analysis, rs2293485 (p=0.034) and rs4717806 (p=0.033) showed nominal associations with HFA; modest haplotype association was also observed. The SNPs that showed associations were related to early developmental abnormalities (ADI-R_D). We further compared STX1A mRNA expression in the lymphocytes of drug-naive HFA patients (n=12) and age- and sex-matched controls (n=13). STX1A expression in the HFA group was significantly higher (p=0.001) than that of controls. Thus, we suggest a possible role of STX1A in the pathogenesis of HFA. During early childhood, there is a period of high brain serotonin synthesis that is disrupted in autistic children; STX1A might influence the serotonergic system during this stage of neurodevelopment, as implied by the association with ADI-R_D.
This paper deals with a problem of nondestructive testing for a composite system formed by the connection of a steel beam and a reinforced concrete beam. The small vibrations of the composite beam are described by a differential system where a coupling takes place between longitudinal and bending motions. The motion is governed in space by two second order and two fourth order differential operators, which are coupled in the lower order terms by the shearing, k, and axial, μ, stiffness coefficients of the connection. The coefficients k and μ define the mechanical model of the connection between the steel beam and the concrete beam and contain direct information on the integrity of the system. In this paper we study the inverse problem of determining k and μ by mixed data. The inverse problem is transformed to a variational problem for a cost function which includes boundary measurements of Neumann data and also some interior measurements. By computing the Gateaux derivatives of the functional, an algorithm based on the projected gradient method is proposed for identifying the unknown coefficients. The results of some numerical simulations on real steel-concrete beams are presented and discussed.