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1.  Evaluation of psychological distress using the K6 in patients on chronic hemodialysis 
Objective
The aim of this study was to evaluate psychological distress in patients on chronic hemodialysis.
Subjects and methods
A total of 72 patients on chronic hemodialysis were enrolled in this study. We evaluated psychological distress by using the K6 questionnaire, health-related quality of life (HRQOL) by using the EQ-5D questionnaire, and clinical parameters. Among the 72 patients, we also evaluated changes in K6 scores in 58 patients at 1-year follow-up.
Results
The mean K6 score was 3.7 ± 3.7 and 2 subjects (2.8 %) were defined as having psychological distress. K6 scores were significantly correlated with body fat percentage, albumin level, and EQ-5D scores in total subjects. K6 scores were also significantly and negatively correlated with EQ-5D scores in men and women. In the 1-year follow-up group, changes in K6 scores were weakly and negatively correlated with changes in EQ-5D scores.
Conclusion
Psychological distress was closely associated with HRQOL in patients on chronic hemodialysis. Coping strategies for psychological distress might be useful in improving HRQOL in patients on hemodialysis.
doi:10.1007/s12199-014-0432-4
PMCID: PMC4597344  PMID: 25472901
Psychological distress; HRQOL; Hemodialysis; K6 questionnaire; EQ-5D questionnaire
2.  Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics 
PLoS ONE  2016;11(1):e0146335.
Background
Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.
Methodology/Principal Findings
Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake.
doi:10.1371/journal.pone.0146335
PMCID: PMC4701477  PMID: 26731104
3.  The linkage among ambulance transports, death and climate parameters in Asahikawa City, Japan 
Objective
The aim of this study was to investigate the linkage among climate parameters, total ambulance transports and the number of deaths in Asahikawa City in northern Japan.
Methods
Monthly data on total ambulance transports and the number of deaths from January 2004 to December 2011 were obtained from Asahikawa City Fire Department and the Asahikawa City official website. Climate parameters for the required period were also obtained from the Japan Meteorological Agency, Japan. To adjust for the population, we also used monthly population data on Asahikawa City. The linkage among climate parameters, total ambulance transports and the number of deaths was evaluated by ecological analysis.
Results
The mean air temperature in the Asahikawa area was 7.3 ± 10.1 °C. Total ambulance transports (/a hundred thousand people/day) and the number of deaths (/a hundred thousand people/day) were 10.0 ± 0.6 and 2.6 ± 0.3, respectively. Using quadratic curves, total ambulance transports and the number of deaths were weakly correlated with some climate parameters. The number of deaths was weakly and positively correlated with total ambulance transports.
Conclusion
A weak linkage among climate parameters, total ambulance transports and the number of deaths was noted in Asahikawa City, Japan. However, these associations were not as high as expected.
doi:10.1007/s12199-014-0429-z
PMCID: PMC4284251  PMID: 25466262
Ambulance transports; Death; Climate parameters; Air temperature; Asahikawa
4.  Perinatal outcomes for transfer of blastocysts vitrified and warmed in defined solutions with recombinant human albumin: 374 babies born after 898 embryo transfers 
Purpose
To assess the efficacy of a novel, defined vitrification procedure using recombinant human albumin (rHA) for cryopreservation of human blastocysts. Design: Retrospective study. Setting: Private IVF clinic. Patients: 1,496 patients received vitrified/warmed embryo transfer (ET).
Methods
Surplus blastocysts, and blastocysts from patients undergoing elective embryo cryopreservation, were vitrified/warmed using Cryotop carriers in homemade solutions containing either human serum albumin (HSA) or rHA. Main Outcome Measures: Clinical and neonatal outcomes regarding the vitrified/warmed ET procedures.
Results
The HSA and rHA groups had a total of 1,163 and 898 vitrified/warmed cycles, respectively. Embryo survival rates (98.7 % vs. 98.9 %, respectively) and the number of embryos transferred (1.08 ± 0.01 vs. 1.06 ± 0.01, respectively) were similar in the HSA and rHA groups. Clinical pregnancy rates/ET were higher (P < 0.05) in the rHA group (56.0 %) than in the HSA group (51.5 %). The HSA and rHA groups had similar live delivery rates/pregnancy (72.2 % vs. 72.3 %, respectively) and perinatal outcomes, including birth weight (2,988 ± 28 vs. 3,046 ± 26 g, respectively). Birth defects occurred in 0.9 % and 1.6 % of neonates in the HSA and rHA groups, respectively.
Conclusions
rHA effectively replaced HSA for human embryo vitrification procedures, and yielded high rates of pregnancy and live births after vitrified/warmed ET. This new approach will support the development of defined ART systems, which will eliminate the variation and risks associated with the use of blood-derived products.
doi:10.1007/s10815-014-0343-8
PMCID: PMC4250466  PMID: 25326854
Blastocyst; Human; Vitrification; Defined; Recombinant human albumin
5.  Developmental capacity and implantation potential of the embryos with multinucleated blastomeres 
The presence of multinucleated blastomeres (MNBs) in embryos is associated with poor developmental competence in assisted reproductive technologies. This phenomenon is observed not only in humans but also in other animal species. The purpose of the present study was to investigate the characteristics of embryos with MNBs (MNB embryos) that could be utilized in embryo transfer. The developmental rate of MNB embryos to the blastocyst stage (50.8%) was significantly lower than that of normal embryos (73.3%) (P < 0.05). The clinical pregnancy rates of fresh embryo transfer (ET) using day 2 or day 3 embryos were significantly lower in MNB embryos (5.1%) compared with normal embryos (24.0%) (P < 0.05). In the case of frozen-thawed ET using a single vitrified/warmed blastocyst, however, the clinical pregnancy rate of MNB embryos was close to that of normal embryos (59.1% vs. 52.8%). Thus, the findings of the present study suggest that the frozen-thawed ET of MNB embryos might improve the potential for implantation followed by successful pregnancy.
doi:10.1262/jrd.2015-052
PMCID: PMC4685227  PMID: 26346255
Blastocyst transfer; Human embryos; Implantation; Multinucleated blastomeres
6.  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
7.  Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis 
BMJ Open  2015;5(4):e007766.
Objectives
To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON.
Setting
We recruited participants in the department of neurology and ophthalmology in our hospital in Japan.
Methods
We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay.
Participants
Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16–84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald's criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16–84 years).
Results
27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy.
Conclusions
Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON.
doi:10.1136/bmjopen-2015-007766
PMCID: PMC4390681  PMID: 25838512
8.  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
9.  Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica 
BBA Clinical  2015;3:126-134.
Background
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-β treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood.
Methods
OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber.
Results
Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin αvβ3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways.
Conclusion
These results indicate that osteopontin is involved in NMO pathology.
General significance
Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO.
Highlights
•Osteopontin is significantly increased in the CSF of NMO patients.•Osteopontin is markedly elevated in the cerebral white matter of NMO patients.•NMO osteopontin is produced by astrocytes, neurons, oligodendroglia, and macrophages.•Interaction of NMO osteopontin with integrin αvβ3 promotes macrophage chemotaxis.•NMO osteopontin promotes macrophage chemotaxis by activating PI3K and MEK1/2.
doi:10.1016/j.bbacli.2015.01.003
PMCID: PMC4661545  PMID: 26673877
Ab, antibody; Abs, antibodies; AQP4, aquaporin-4; CNS, central nervous system; CSF, cerebrospinal fluid; EAE, experimental autoimmune encephalomyelitis; GFAP, glial fibrillary acidic protein; IFN, interferon; mAb, monoclonal antibody; MS, multiple sclerosis; NMO, neuromyelitis optica; OPN, osteopontin; pAb, polyclonal antibody; PI3K, phosphoinositide 3-kinase; RGD, Arg–Gly–Asp; RGE, Arg–Gly–Glu; TRAP, tartrate-resistant form of acid phosphatase; Osteopontin; Neuromyelitis optica; Cerebrospinal fluid; Multiple sclerosis; Biomarker; Integrin
10.  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
11.  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
12.  Phylogenetic Clades 6 and 8 of Enterohemorrhagic Escherichia coli O157:H7 With Particular stx Subtypes are More Frequently Found in Isolates From Hemolytic Uremic Syndrome Patients Than From Asymptomatic Carriers 
Open Forum Infectious Diseases  2014;1(2):ofu061.
EHEC O157:H7 clade 6 strains harboring stx2a and/or stx2c and clade 8 strains harboring stx2a or stx2a/stx2c were frequently associated with childhood HUS cases in Japan. Rapid and specific detection of such lineages are required for infection control measures.
Background
 Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe diseases such as bloody diarrhea and hemolytic uremic syndrome (HUS). Although EHEC O157:H7 strains have exhibited high genetic variability, their abilities to cause human diseases have not been fully examined.
Methods
 Clade typing and stx subtyping of EHEC O157:H7 strains, which were isolated in Japan during 1999–2011 from 269 HUS patients and 387 asymptomatic carriers (ACs) and showed distinct pulsed-field gel electrophoresis patterns, were performed to determine relationships between specific lineages and clinical presentation.
Results
 Clades 6 and 8 strains were more frequently found among the isolates from HUS cases than those from ACs (P = .00062 for clade 6, P < .0001 for clade 8). All clade 6 strains isolated from HUS patients harbored stx2a and/or stx2c, whereas all clade 8 strains harbored either stx2a or stx2a/stx2c. However, clade 7 strains were predominantly found among the AC isolates but less frequently found among the HUS isolates, suggesting a significant association between clade 7 and AC (P < .0001). Logistic regression analysis revealed that 0–9 year old age is a significant predictor of the association between clade 8 and HUS. We also found an intact norV gene, which encodes for a nitric oxide reductase that inhibits Shiga toxin activity under anaerobic condition, in all clades 1–3 isolates but not in clades 4–8 isolates.
Conclusions
 Early detection of EHEC O157:H7 strains that belonged to clades 6/8 and harbored specific stx subtypes may be important for defining the risk of disease progression in EHEC-infected 0- to 9-year-old children.
doi:10.1093/ofid/ofu061
PMCID: PMC4281788  PMID: 25734131
clade; EHEC; HUS; O157; stx
13.  Anti-inflammatory effects of green soybean extract irradiated with visible light 
Scientific Reports  2014;4:4732.
We conducted a preliminary investigation of the effects of visible light irradiation on plant extracts, and we observed a strong suppressive effect on interleukin (IL) 2 expression with the inhibition of c-Jun amino-terminal kinase (JNK) phosphorylation in Jurkat cells by visible light irradiation to ethanol extract from green soybeans (LIEGS). This effect was produced only by extracts from green soybeans (Glycine max) and not other-color soybeans. LIEGS suppressed the lipopolysaccharide-induced IL-6, IL-12 and TNF-α expression levels in human monocyte THP-1 cells in a concentration-dependent manner. LIEGS was applied for 8 weeks to NC/Nga mice. LIEGS suppressed the development of atopic dermatitis (AD)-like skin lesions and reduced the dermatitis scores of the mice. The light irradiation changed the various types of small-molecule compounds in extracts. Visible light irradiation to daidzein with chlorophyll b induced a novel oxidative product of daidzein. This product suppressed IL-2 expression in Jurkat cells.
doi:10.1038/srep04732
PMCID: PMC3994445  PMID: 24751752
14.  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
15.  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
16.  Evolutionary Relations of Hexanchiformes Deep-Sea Sharks Elucidated by Whole Mitochondrial Genome Sequences 
BioMed Research International  2013;2013:147064.
Hexanchiformes is regarded as a monophyletic taxon, but the morphological and genetic relationships between the five extant species within the order are still uncertain. In this study, we determined the whole mitochondrial DNA (mtDNA) sequences of seven sharks including representatives of the five Hexanchiformes, one squaliform, and one carcharhiniform and inferred the phylogenetic relationships among those species and 12 other Chondrichthyes (cartilaginous fishes) species for which the complete mitogenome is available. The monophyly of Hexanchiformes and its close relation with all other Squaliformes sharks were strongly supported by likelihood and Bayesian phylogenetic analysis of 13,749 aligned nucleotides of 13 protein coding genes and two rRNA genes that were derived from the whole mDNA sequences of the 19 species. The phylogeny suggested that Hexanchiformes is in the superorder Squalomorphi, Chlamydoselachus anguineus (frilled shark) is the sister species to all other Hexanchiformes, and the relations within Hexanchiformes are well resolved as Chlamydoselachus, (Notorynchus, (Heptranchias, (Hexanchus griseus, H. nakamurai))). Based on our phylogeny, we discussed evolutionary scenarios of the jaw suspension mechanism and gill slit numbers that are significant features in the sharks.
doi:10.1155/2013/147064
PMCID: PMC3780621  PMID: 24089661
17.  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
18.  The role of tobacco use on dental care and oral disease severity within community dental clinics in Japan 
Tobacco Induced Diseases  2013;11(1):13.
Background
To examine facilitators of dental smoking intervention practices in Japan, where smokeless tobacco is rarely used, we evaluated the characteristics of dental care for smokers.
Methods
Community dentists volunteered to record the treated disease or encounter with patients that was principally responsible for their dental care on the survey day. Patients were classified into groups receiving gingival/periodontal treatment (GPT), caries/endodontic treatment (CET), prosthetic treatment (PRT), periodical check-up/orthodontic treatment (POT), or other encounters/treatments. Potential effect of dentist clustering was adjusted by incorporating the complex survey design into the analysis.
Results
Data of 2835 current smokers (CS) and 6850 non-smokers (NS) from 753 clinics were analysed. Distribution of treatments significantly differed between CS and NS (P = 0.001). In ad hoc multiple comparisons for each treatment, CS were significantly higher than NS for CET (47.1% vs. 43.6%, P = 0.002), and lower for POT (1.6% vs. 2.7%, P = 0.001), whereas GPT and PRT proportions were equivalent by smoking. When stage of disease progression was compared in the GPT subpopulation, CS were more likely received treatment for advanced stage disease than NS in the age groups of 40–59 years (24.9% vs. 15.3%, P = 0.001) and more than 60 years (40.8% vs. 22.1%, P < 0.001). However, the difference was less apparent in the entire population (9.7% vs. 6.0%), and CS were not predominant among patients receiving GPT for advanced stage disease (37.6%).
Conclusions
The association of smoking with type of dental care of CET and GPT severity would warrant the need for dental professionals to engage their patients smoking within clinical practice. The detrimental effects of smoking in dental care for smokers, as evidenced by the distribution of treatment and encounter and stage of treated disease, may not be clearly realized by dental professionals, unless the smoking status of all patients is identified.
doi:10.1186/1617-9625-11-13
PMCID: PMC3701518  PMID: 23799972
Dental care; Dental caries; Dental clinic; Periodontal disease; Prosthetic treatment; Smoking
19.  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
20.  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
21.  Memory Immune Responses against Pandemic (H1N1) 2009 Influenza Virus Induced by a Whole Particle Vaccine in Cynomolgus Monkeys Carrying Mafa-A1*052∶02 
PLoS ONE  2012;7(5):e37220.
We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA) non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009) H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052∶02, were used to analyze peptide-specific CD8+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1) than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1) in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052∶02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses to macaques against pandemic influenza virus infection than did the split vaccine.
doi:10.1371/journal.pone.0037220
PMCID: PMC3356377  PMID: 22623997
22.  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
23.  Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features 
BMC Psychiatry  2012;12:37.
Background
Causative role of encephalitis in major psychotic features, dyskinesias (particularly orofacial), seizures, and autonomic and respiratory changes has been recently emphasized. These symptoms often occur in young females with ovarian teratomas and are frequently associated with serum and CSF autoantibodies to the NMDA receptor (NMDAR).
Methods
The study included a total of 61 patients from age 15 to 61 and was carried out between January 1, 2005, and Dec 31, 2010. The patients were divided into the following three clinical groups for comparison. Group A; Patients with typical clinical characteristics of anti-NMDAR encephalitis. Group B; Patients with narcolepsy with severe psychosis. Group C; Patients with schizophrenia or schizo-affective disorders.
Results
Ten out of 61 cases were anti-NMDAR antibody positive in typical encephalitis cases (group A: 3 of 5 cases) and cases in a broader range of psychiatric disorders including narcolepsy (group B: 3 of 5 cases) and schizophrenia (group C: 4 of 51 cases).
Conclusion
In addition to 3 typical cases, we found 7 cases with anti-NMDAR antibody associated with various psychotic and sleep symptoms, which lack any noticeable clinical signs of encephalitis (seizures and autonomic symptoms) throughout the course of the disease episodes; this result suggest that further discussion on the nosology and pathophysiology of autoimmune-mediated atypical psychosis and sleep disorders is required.
doi:10.1186/1471-244X-12-37
PMCID: PMC3436772  PMID: 22569157
24.  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
25.  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

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