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Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1–10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population.
To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH).
Design:
Case–control study.
Setting:
Osaka University Hospital.
Participants:
Patients with possible iNPH underwent a CSF tap test.
Measurements:
Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients.
Results:
We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline.
Conclusions:
A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.
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 analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1–3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.
Cluster of differentiation 36 (CD36) is a membrane receptor expressed on a wide variety of human cells. CD36 polymorphisms are reportedly associated with oral fat perception, dietary intake and metabolic disorders. The present study examined associations of two CD36 polymorphisms (rs1761667 and rs1527483) and dietary fat intake, and metabolic phenotypes in a Japanese population. This cross-sectional study was conducted based on clinical information collected from health check-ups in Japan (n 495). Dietary nutrient intake was estimated from a validated short FFQ and adjusted for total energy intake using the residual method. Mean blood pressure was calculated from systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertension was defined as SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg, or use of antihypertensive drugs. Genotyping was performed using PCR with confronting two-pair primers method. Mean age was 63·4 (sd 9·9) years. Individuals with the AA genotype showed higher total fat and MUFA intake (standardised β = 0·110 and 0·087, P = 0·01 and 0·05, respectively) compared with the GG and GA genotypes. For metabolic phenotypes, the AA genotype of rs1761667 had a lower blood pressure compared with the GG genotype (standardised β = –0·123, P = 0·02). Our results suggested that the AA genotype of rs1761667 in the CD36 gene was associated with higher intake of total fat and MUFA and lower risk of hypertension in a Japanese population.
Unusual mafic rock fragments deposited in Plio-Pleistocene-aged marine sediments were recorded at Integrated Ocean Drilling Program (IODP) Site U1359, in Wilkes Land, East Antarctica. These fragments were identified from sediment layers deposited between c. 3 and 1.2 Ma, indicating a sustained supply during this time interval. Clinopyroxenes in these basalts are Al–Ti diopside–hedenbergite, uncommon in terrestrial magmatic rocks. A single strong peak in the Raman spectra of a phosphate-bearing mineral at 963 cm-1 supports the presence of merrillite. Although not conclusive, petrological traits and oxygen isotopic compositions also suggest that the fragments may be extra-terrestrial fragments affected by shock metamorphism. Nevertheless, it is concluded that the basaltic fragments incorporated in marine sediments at Site U1359 represent ice-rafted material supplied to the continental rise of East Antarctica, probably from the bedrocks near the proximal Ninnis Glacier. Further studies on Plio-Pleistocene sediments near Site U1359 are required to characterize the unusual mafic rocks described.
Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47–69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2–Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.
Neuroimaging studies of depression considered as a stress-related disorder have shown uncoupling in regional cerebral blood flow (rCBF) and regional cerebral metabolic rate for glucose (rCMRglc). We hypothesised that the mismatch change of rCBF and rCMRglc could be a stress-related phenomenon.
Methods
We exposed male rats to 15-min period of forced swim (FS), followed by the measurement of rCBF using N-isopropyl-4-[123I] iodoamphetamine (123I-IMP) and rCMRglc using 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG).
Results
The uptake rate of 18F-FDG in the FS group showed a significant decrease in the prefrontal cortex (0.86±0.20%ID/g, p<0.01) and thalamus (0.77±0.17%ID/g, p<0.05) and tended to be lower in the hippocampus (0.58±0.13%ID/g) and cerebellum (0.59±0.13%ID/g) without overt alteration in the uptake rate of 123I-IMP.
Conclusions
The FS stress can cause mismatch change of rCBF and rCMRglc, which reflect a stress-related phenomenon.
Treatment-resistant depression is a challenging problem in the clinical setting. Tipepidine has been used as a non-narcotic antitussive in Japan since 1959.
Methods
We administered tipepidine to 11 patients with treatment-resistant depression. Tipepidine was given for 8 weeks as an augmentation.
Results
Tipepidine significantly improved depression scores on the Hamilton Rating Scale for depression. Add-on treatment with tipepidine significantly improved scores on the trail making test and Rey auditory verbal learning test. However, no changes were observed in blood concentrations of stress-related hormones (adrenocorticotropic hormone, cortisol, dehydroepiandrosterone sulphate) with tipepidine augmentation.
Conclusion
Tipepidine might be a potential therapeutic drug for treatment-resistant depression.
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 purpose of this study was to qualitatively examine the content of the psychological responses in interviews with breast cancer outpatients receiving initial medical consultation.
Method:
The participants were 180 people who visited the breast cancer outpatient clinic at Kitasato University Hospital between November 2004 and August 2005. The remaining 176 participants (39 breast cancer patients and 137 benign tumor patients; average age ± SD: 50.7 ± 12.4 years) were analyzed. Two clinical psychologists carried out the interview, asking the participants to speak freely about their anxieties, worries, thoughts, and feelings up until the medical examination. This study used a content analysis of interviews to chronologically examine psychological response of cancer patients seeking medical consultation at three points in time.
Results:
Patients at the time of their first outpatient breast cancer consultation experience negative feelings before the examination, directly influenced by the suspicion of cancer. These include anxiety and worries, fear, evasion, depression, and impatience. These tendencies do not change at the time of consultation. However, in addition to negative feelings, some people also possess positive feelings, either simultaneously or at a different point in time. Further, many patients tend to talk at length about psychological responses before seeking treatment, understanding the process they went through to come to seek treatment as an important event.
Significance of results:
It is important for medical workers to bear in mind the psychological conflicts that patients may undergo before seeking treatment and ensure that sufficient communication takes place.
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.
Aims
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).
Method
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
birth order.
Results
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.
Conclusions
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.
This study discusses the pattern of development of child-related policies, particularly in recent years. The Liberal Democratic Party (LDP) lacks interest in public engagement in child-related issues, whereas Komeito, the recent coalition partner of the LDP, has been the driving force of recent developments. The study investigates the historical development of three child-related policies: namely, child allowance, childcare services, and the facilitation of work–life balance of employees, and discusses the role of Komeito in the recent coalition government. An analytical model is provided to explain why Komeito was active in the development of child allowance, but not other policies. On the whole, the participation of Komeito in the coalition government seems to give impetus to the development of child-related polices, but the scope of that party's behavior is constrained, due to its position as a minor partner in the coalition government.
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.
We have investigated the effect of the substrate-surface morphology on the growth of Al whiskers grown by high temperature glancing angle deposition (HT-GLAD). Before the HT-GLAD of Al at 390 °C, the morphology of the substrate was systematically modified by depositing nanocolumnar SiO2 layer of thickness between 0 and 100 nm on the flat SiO2 layer. Aluminum whiskers with the width of ≈100 nm and the length ≤ μm are found on all the samples. The number of short whiskers, which can be grown from very small nuclei, depends strongly on the thickness of the SiO2 nanocolumnar layer and shows the maximum at SiO2 thickness of 20 nm. On the other hand, the number of long whiskers, which requires extraordinary amount of Al than that deposited on the side surface of the whikers, is almost independent of SiO2 thickness. These facts suggest that the surface roughness of the substrate plays an important role in the nucleation of the whiskers and that there are some transport processes of Al, which are insensitive to the surface morphology.
We demonstrated high temperature glancing deposition (HT-GLAD) of Al on the heated substrate with trench patterns. When Al was deposited under the condition, where the Al vapor is incident at very glancing on the sidewall but on the surface, Al nano-whiskers grew only on the sidewall of the trenches since HT-GLAD condition is achieved only for the sidewall. On the other, Al was deposited at glancing angle both on the surface and the sidewalls, nano-whiskers grow both on the surface and the sidewalls of the trenches. The selective growth of the nano-whisker is successfully achieved by controlling the geometrical deposition conditions. Remarkably, moreover, the nano-whiskers grow not only on the illuminated sidewalls but also on the shadow sidewall. In addition, few nano-whiskers grow on the shadow region of the bottom of the trenches. In order to understand the peculiar growth of Al nano-whiskers, novel transport processes of Al atoms other than the surface diffusion have to be clarified. The reevaporation or reflective scattering on the sidewalls of the trenches is likely to play an important role in the growth of nano-whiskers.
We demonstrate high temperature glancing deposition (HT-GLAD) of metals on the heated substrate. It has been found that Al, Ag, Au, Fe nano-whiskers grow on the substrate of Si, SiO2, and glass substrates. The robustness in the selection of materials suggests that the HT-GLAD is a universal method to grow nano-whiskers of various metals. We also demonstrate the selective growth of the nano-whiskers on the substrate with micro-trench patterns. The metal nano-whiskers are useful for the nano electromechanical devices and vacuum microelectronics.