Risk factor profile for newly diagnosed atrial fibrillation: 4-year follow-up of annual health examinations in a Japanese Adult Cohort.

Background: Detecting unknown atrial fibrillation (AF) would provide an opportunity to prevent ischemic stroke by instituting appropriate anticoagulation. Although opportunistic screening of older patients is recommended in current guidelines, which patients may benefit from intensive AF screening remains unclear. We sought to clarify the risk factor profile for newly diagnosed AF in annual health examinations of a Japanese adult cohort. Methods: Among 141 441 Japanese patients who underwent annual health examinations in 2014, 87 872 patients aged ≥20 years without known AF who had undergone electrocardiography were analyzed (mean age: 47 ± 12 years; 64% men). The absence of known AF was confirmed by prior electrocardiography in 2012 and/or 2013. Newly diagnosed AF was observed in 244 patients in 2014-2017 (mean age: 62 ± 12 years; 83% men). Results: In the multivariable analysis, waist circumference obesity (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.13-1.99; p = .005) high blood pressure (HR, 1.9; 95% CI, 1.01-3.59; p = .047), on-treatment hypertension (HR, 1.53; 95% CI, 1.01-2.31; p = .046), and daily alcohol drinking (HR, 2.18; 95% CI, 1.52-3.12; p < .001) were significantly associated with newly diagnosed AF. Conclusions: In this Japanese cohort, waist circumference obesity, hypertension, and alcohol drinking were independent predictors of newly diagnosed AF in annual medical examinations. This finding encourages further evaluation of systematic AF screening programs in at-risk populations.

High prevalence of fragmented QRS on electrocardiography in Japanese patients with diabetes irrespective of metabolic syndrome.

AIMS/INTRODUCTION: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. MATERIALS AND METHODS: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets-; 103 participants); diabetes mellitus- MetS+ (133 participants); and diabetes mellitus- MetS- (302 participants). fQRS was assessed using the results of electrocardiography. RESULTS: The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS- (35%), than those with diabetes mellitus- MetS+ (14%) or diabetes mellitus- MetS- (10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(-) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67-0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62-0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25-5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference. CONCLUSIONS: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.

Incremental yield of ECG screening repeated annually over 4 years in an adult Japanese population without prior atrial fibrillation: a retrospective cohort study.

OBJECTIVES: International guidelines recommend opportunistic screening for atrial fibrillation (AF); however, there is no current data to inform how often to repeat screening. We aimed to investigate the incremental annual yield and stroke risk of new AF cases in individuals screened annually over 4 years. DESIGN: A retrospective cohort study. SETTING: Hokuriku Health Service Association, Toyama prefecture, Japan. PARTICIPANTS: Employees and their families receiving annual health examinations from Hokuriku Health Service Association. INTERVENTION: Each subject received an annual health examination (including 12-lead ECG) from 2014 to 2017. Only subjects with baseline ECGs in 2012 and/or 2013 were included. MAIN OUTCOME MEASURES: Rates (cases/100 person-years) of new AF identified each year for 4 consecutive years of screening (stratified according to gender and age groups). Calculated stroke risk of new AF cases using modified CHA2DS2-VASc scores (without heart failure data) (CHA2DS2VASc = C: congestive heart failure [1 point]; H: hypertension [1 point]; A2: age 65-74 years [1 point] or age ≥75 years [2 points]; D: diabetes mellitus [1 point]; S: prior stroke or transient ischemic attack [2 points]; VA: vascular disease [1 point]; and Sc: sex category [female] [1 point]) RESULTS: In 2014, 88 218 subjects had an ECG (46.8±12.5 years; 64% men): identifying 346 (0.39%) known AF and 69 (0.08%) new AF. The incidence rate of new AF increased with age from 0.01% (<50 years) to 0.98% (≥75 years) and was higher in men (0.1%) than women (0.05%). Repeated annual screening over 4 years identified a consistent new AF yield 0.06%-0.10% per year (0.33%-0.55% ≥65 years). Forty-two per cent of all new AF cases, and 76% of cases aged ≥65 years, had a class-1 oral anticoagulation (OAC) recommendation (modified CHA2DS2-VASc score ≥2 men, ≥3 women). CONCLUSIONS: Repeated annual ECG screening of the same population provides a consistent yield of new AF each year. The majority of new AF (≥65 years) are eligible for anticoagulation for stroke prevention. Although AF prevalence and incidence are lower in Japan than Western countries, 2318 new cases would be identified in Toyama prefecture each year with annual screening, of whom ~927 would have a high stroke risk with a recommendation for OAC therapy.

Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons.

The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons.

Transient activation of Wnt/ß-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.

After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/ß-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(-) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/ß-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury.

Cohort Profile: The Japanese Population-based Osteoporosis (JPOS) Cohort Study.

The Japanese Population-based Osteoporosis (JPOS) Cohort Study was launched in 1996 to produce a reference database of areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA) and bone turnover markers in the Japanese female population and to determine risk factors for osteoporotic fractures. At baseline, 3984 women aged 15 to 79 years were randomly selected to provide representative bone status data and aBMD values for the diagnosis of osteoporosis. Follow-up surveys were conducted in 1999, 2002, 2006 and 2011/12 to determine changes in aBMD and identify incident morphometry-confirmed vertebral fractures and clinical fractures. These outcomes were obtained from 2174 women who participated in at least one follow-up survey. JPOS is a unique resource of individual-level bone health information with radiological and biological archives that include DXA images, and serum, plasma and DNA for future analyses with emerging radiological and biological techniques. The JPOS dataset is not freely available, but new collaborations are encouraged. Potential collaborators are invited to contact the Secretary General (M.I.) at the administrative office of the JPOS Study Group.

Pax6 mediates ß-catenin signaling for self-renewal and neurogenesis by neocortical radial glial stem cells.

The Wnt/ß-catenin pathway is a critical stem cell regulator and plays important roles in neuroepithelial cells during early gestation. However, the role of Wnt/ß-catenin signaling in radial glia, a major neural stem cell population expanded by midgestation, remains poorly understood. This study shows that genetic ablation of ß-catenin with hGFAP-Cre mice inhibits neocortical formation by disrupting radial glial development. Reduced radial glia and intermediate progenitors are found in the ß-catenin-deficient neocortex during late gestation. Increased apoptosis and divergent localization of radial glia in the subventricular zone are also observed in the mutant neocortex. In vivo and in vitro proliferation and neurogenesis as well as oligodendrogenesis by cortical radial glia or by dissociated neural stem cells are significantly defective in the mutants. Neocortical layer patterning is not apparently altered, while astrogliogenesis is ectopically increased in the mutants. At the molecular level, the expression of the transcription factor Pax6 is dramatically diminished in the cortical radial glia and the sphere-forming neural stem cells of ß-catenin-deficient mutants. Chromatin immunoprecipitation and luciferase assays demonstrate that ß-catenin/Tcf complex binds to Pax6 promoter and induces its transcriptional activities. The forced expression of Pax6 through lentiviral transduction partially rescues the defective proliferation and neurogenesis by ß-catenin-deficient neural stem cells. Thus, Pax6 is a novel downstream target of the Wnt/ß-catenin pathway, and ß-catenin/Pax6 signaling plays critical roles in self-renewal and neurogenesis of radial glia/neural stem cells during neocortical development.

EphB2 isolates a human marrow stromal cell subpopulation with enhanced ability to contribute to the resident intestinal cellular pool.

To identify human bone marrow stromal cell (BMSC) subsets with enhanced ability to engraft/contribute to the resident intestinal cellular pool, we transplanted clonally derived BMSCs into fetal sheep. Analysis at 75 d post-transplantation showed 2 of the 6 clones engrafting the intestine at 4- to 5-fold higher levels (5.03±0.089 and 5.04±0.15%, respectively) than the other clones (P<0.01), correlating with the percentage of donor-derived Musashi-1(+) (12.01-14.17 vs. 1.2-3.8%; P<0.01) or leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)(+) cells within the intestinal stem cell (ISC) region. Phenotypic and transcriptome analysis determined that the clones with enhanced intestinal contribution expressed high levels of Ephrin type B receptor 2 (EphB2). Intestinal explants demonstrated proliferation of the engrafted cells and ability to generate crypt-like structures in vitro still expressing EphB2. Additional transplants based on BMSC EphB2 expression demonstrated that, at 7 d post-transplant, the EphB2(high) BMSCs engrafted in the ISC region at levels of 2.1 ± 0.2%, while control EphB2(low) BMSCs engrafted at 0.3 ± 0.1% (P<0.01). Therefore we identified a marker for isolating and culturing an expandable subpopulation of BMSCs with enhanced intestinal homing and contribution to the ISC region.

Deoxidation of fenthion sulfoxide, fenthion oxon sulfoxide and fensulfothion in gas chromatograph/mass spectrometer, and the prevention of sulfoxide deoxidation by polyethylene glycol 300.

Fenthion, fenthion sulfoxide, fenthion oxon sulfoxide and fensulfothion showed two different mass spectra in GC/MS, depending on their concentrations. The base peaks shifted to lower levels by 1 m/z at lower concentration, and no retention time shifts were observed. The "shifted base peaks" were not obtained by a general EI fragmentation. The product ion scan spectra of the "shifted base peaks" were coincident with those of molecular ions of their corresponding sulfides. These phenomena can be ascribed to the conversion of sulfoxide into sulfide by the dominant deoxidation reaction than EI fragmentation in an ion source. Adding polyethylene glycol 300 (PEG300) into a test solution prevented sulfoxide deoxidation.

Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration.

The mammalian olfactory epithelium (OE) has a unique stem cell or progenitor niche, which is responsible for the constant peripheral neurogenesis throughout the lifespan of the animal. However, neither the signals that regulate the behavior of these cells nor the lineage properties of the OE stem cells are well understood. Multiple Wnt signaling components exhibit dynamic expression patterns in the developing OE. We generated Wnt signaling reporter TOPeGFP transgenic mice and found TOPeGFP activation predominantly in proliferating Sox2(+) OE basal cells during early postnatal development. FACS-isolated TOPeGFP(+) OE basal cells are required, but are not sufficient, for formation of spheres. Wnt3a significantly promotes the proliferation of the Sox2(+) OE sphere cells. Wnt-stimulated OE sphere cells maintain their multipotency and can differentiate into most types of neuronal and non-neuronal epithelial cells. Also, Wnt activators shift the production of differentiated cells toward olfactory sensory neurons. Moreover, TOPeGFP(+) cells are robustly increased in the adult OE after injury. In vivo administration of Wnt modulators significantly alters the regeneration potential. This study demonstrates the role of the canonical Wnt signaling pathway in the regulation of OE stem cells or progenitors during development and regeneration.

Tracking of appendicular bone mineral density for 6 years including the pubertal growth spurt: Japanese Population-based Osteoporosis kids cohort study.

Bone development up to early adulthood plays an important role in determining the risk of osteoporosis later in life. However, bone development in children has not been fully documented by longitudinal studies in Japanese children. The purpose of this study is to determine the degree of tracking of areal bone mineral density (aBMD) from pre-puberty to 6-year follow-up, and to determine the target period to achieve maximal peak aBMD. This study was conducted as the pediatric part of a larger cohort study, the Japanese Population-based Osteoporosis (JPOS) study. Of 448 children aged 9-12 years who completed the baseline survey, 225 participated in the follow-up study 6 years later (follow-up rate: 50.2%). aBMD at the forearm was measured using dual-energy X-ray absorptiometry. aBMD values in pre-pubertal children at baseline showed a significant tracking correlation with aBMD obtained at 6-year follow-up in both genders (boys r = 0.655, girls r = 0.759). Although boys and girls in the lowest quartile of aBMD pre-pubertally had greater annual increases in aBMD from pre-puberty to 6-year follow-up than those in other aBMD quartiles, they still showed the lowest mean aBMD at 6-year follow-up. Children with lower pre-pubertal aBMD showed greater increases in BMD up until 6-year follow-up, but the increase was not great enough to catch up with other children. About 50% of the variance in aBMD at 6-year follow-up was determined by the aBMD achieved during the pre-pubertal period. Activities that increase aBMD are important not only for children during puberty, but also for younger pre-pubertal children.

Epithelial Wnt/ß-catenin signaling regulates palatal shelf fusion through regulation of Tgfß3 expression.

The canonical Wnt/ß-catenin signaling plays essential role in development and diseases. Previous studies have implicated the canonical Wnt/ß-catenin signaling in the regulation of normal palate development, but functional Wnt/ß-catenin signaling and its tissue-specific activities remain to be accurately elucidated. In this study, we show that functional Wnt/ß-catenin signaling operates primarily in the palate epithelium, particularly in the medial edge epithelium (MEE) of the developing mouse palatal shelves, consistent with the expression patterns of ß-catenin and several Wnt ligands and receptors. Epithelial specific inactivation of ß-catenin by the K14-Cre transgenic allele abolishes the canonical Wnt signaling activity in the palatal epithelium and leads to an abnormal persistence of the medial edge seam (MES), ultimately causing a cleft palate formation, a phenotype resembling that in Tgfß3 mutant mice. Consistent with this phenotype is the down-regulation of Tgfß3 and suppression of apoptosis in the MEE of the ß-catenin mutant palatal shelves. Application of exogenous Tgfß3 to the mutant palatal shelves in organ culture rescues the midline seam phenotype. On the other hand, expression of stabilized ß-catenin in the palatal epithelium also disrupts normal palatogenesis by activating ectopic Tgfß3 expression in the palatal epithelium and causing an aberrant fusion between the palate shelf and mandible in addition to severely deformed palatal shelves. Collectively, our results demonstrate an essential role for Wnt/ß-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgfß3 in the MEE.

Generation of Lrp6 conditional gene-targeting mouse line for modeling and dissecting multiple birth defects/congenital anomalies.

Lrp6 is a key coreceptor in the canonical Wnt pathway that is widely involved in tissue/organ morphogenesis. We generated a loxP-floxed Lrp6 mouse line. Crossing with a general Cre deleter, we obtained the Lrp6-floxdel mice, in which the loxP-floxed exon 2 of Lrp6 gene has been deleted ubiquitously. The homozygotes of Lrp6-floxdel mice reproduced typical defects as seen in the conventional Lrp6-deficient mice, such as defects in eye, limb, and neural tube, and die around birth. We also found new phenotypes including cleft palate and agenesis of external genitalia in the Lrp6-floxdel mice. In addition, the Lrp6-deficient embryos are known to be defective in other systems and internal organs including the heart and brain. Thus, by selectively crossing with a lineage-specific or inducible Cre mouse line, the Lrp6 conditional gene-targeting mice will allow us to model specific types of birth defects for mechanism and prevention studies.

Canonical Wnt signaling activity during synovial joint development.

Wnt signaling plays important roles in skeletal development. However, the activation and function of canonical Wnt signaling in joint development remains unclear. We analyzed the lineage identity and developmental changes of the Wnt-responsive cells during synovial joint formation as well as adulthood in the Wnt signaling reporter TOPgal transgenic mice. At embryonic day (E) 12.5, we found that the TOPgal was inactivated in the presumptive joint forming interzone, but it was intensively activated in the cartilage anlage of developing long bones and digits. At E14.5, the TOPgal activity was found in a subgroup of the articular chondrocyte lineage cells, which were co-immunolabeled with Doublecortin intensively and with Vinculin weakly. At E18.5, the TOPgal/Doublecortin co-immunolabeled cells were found in the superficial layer of the developing articular cartilage. During postnatal development, the TOPgal(+) articular chondrocytes were abundant at P7 and decreased from P10. A small number of TOPgal(+) articular chondrocytes were also found in adult joints. Our study suggests an age- and lineage-specific role of canonical Wnt signaling in joint development and maintenance.

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion.

Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/beta-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/beta-catenin signaling pathway during lip formation and fusion. By contrast, a ;fusion-resistant' gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/beta-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.

Relationship between body image and lifestyle factors in Japanese adolescent girls.

BACKGROUND: Body image, defined here as an inaccurate perception of personal bodyweight, plays a significant role in the development of obesity, eating problems and eating disorders. Certain lifestyle factors may influence an individual's body image, but current knowledge is based mainly on studies in Western populations. METHODS: The associations between body image and lifestyle factors were investigated in samples of the Japanese female adolescent population. RESULTS: Respondents who reported that they ate meals slowly (odds ratio [OR] 1.81, P < 0.001) or only consumed small amounts of food (OR 3.17, P < 0.001) were more likely to underestimate their body image, as determined by their body mass index, than eaters who had average behavior for this age group. Individuals who reported eating faster (OR 1.47, P < 0.001) or consuming large amounts (OR 1.67, P < 0.001); those who do not eat breakfast on a daily basis (OR 1.35, P = 0.006); those who go to bed later than the average time for this age group (OR 1.38, P < 0.001) or sleep <7 h (OR 1.40, P < 0.001) and those individuals who rarely exercise (OR 1.27, P = 0.03) were more likely to overestimate their body image, as determined by BMI, compared with those who had average eating, sleeping and exercise behaviors for this age group. CONCLUSIONS: Variation from the norm in eating, sleeping and exercise behaviors showed a relationship with a distorted perception of body image in Japanese adolescent girls. These findings are of potential importance in understanding the underlying mechanisms involved in the development of body image and for exploring interventional approaches.

Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line.

Acute myeloid leukemia (AML) is the most frequently diagnosed adulthood leukemia, yet current therapies offer a cure rate of less than 30%. This may be due in part to the fact that the leukemia-initiating cells in AML reside within the rare and highly primitive CD34(+)CD38(-) hematopoietic stem/progenitor cell (HSC) population that are often resistant to chemotherapy. Docosahexanoic acid (DHA), a major component of fish oil, has previously been shown to inhibit the induction and progression of breast, prostate and colon cancer, and increase the therapeutic effects of numerous chemotherapeutics, often by enhancing apoptosis. In the present studies, we investigated DHA's effect on the primitive and undifferentiated AML cell line KG1a, to explore the potential of this fatty acid to serve as adjuvant therapy for AML. Treatment of KG1a cells with DHA for 96 hours did not lead to maturation or cell cycle modification when compared to an untreated KG1a control (n = 4). However, DHA treatment of KG1a cells resulted in a progressive loss of viability, DNA fragmentation, and an increase in Annexin V expression, demonstrating DHA-induced apoptosis (n = 4). Moreover, expression of the pro-apoptotic protein Bax was increased, with resultant skewing in the Bax/bcl-2 ratio, providing a mechanistic explanation for the observed DHA-induced increase in apoptosis. Since we also show that DHA does not have a detrimental effect on normal hematopoiesis our results suggest that DHA could potentially serve as an well-tolerated adjuvant in the treatment of AML patients.

Lifestyle at 3 years of age and quality of life (QOL) in first-year junior high school students in Japan: results of the Toyama Birth Cohort Study.

OBJECTIVE: The aim of this study was to determine whether some effects of childhood lifestyles at 3 years of age are associated with quality of life (QOL) in first-year junior high school students (JHSS). METHOD: Lifestyles including sleep, physical activity and dietary habits of 9,674 3-year-old children were obtained by questionnaire between 1992 and 1994. Assessments were undertaken with the Dartmouth Primary Care Co-operative Project charts in 9,574 first-year JHSS in 2002. Logistic regression analyses were used to explore the relationship between lifestyle in early childhood and QOL in first-year JHSS for the follow-up subjects. RESULTS: After adjusting for demographic and familial factors at baseline, the results showed that later bedtime [odds ratio (OR) = 1.17, P = 0.043], later waking time (OR = 1.19, P = 0.039), short sleep duration (OR = 1.15, P = 0.061), physical inactivity (OR = 1.48, P = 0.022), skipping breakfast (OR = 1.56, P = 0.003), irregular snacks (OR = 1.43, P < 0.001), and frequent instant noodle consumption (OR = 1.49, P = 0.007) in early childhood increased the risk of poor QOL in first-year JHSS. The relationships were reinforced by a significant linear trend for almost all factors considered at baseline to QOL in first-year JHSS. CONCLUSION: Early childhood lifestyle factors, especially dietary habits, at 3 years of age have significant effects on QOL in first-year JHSS. This suggests that interventions as early as 3 years of age should be considered.

Biological variations in cadmium, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in adult women in a non-polluted area.

OBJECTIVES: This study was initiated to investigate the extents of biological variations in cadmium and three common tubular dysfunction marker levels in blood and urine through repeated sampling. METHODS: A 12-month survey and a 10-week survey were conducted in an area with no known cadmium pollution. In the 12-month survey, five adult women offered urine samples once every month and blood samples once in every season, respectively. In the 10-week survey, 17 adult women gave urine samples once every week. Blood and urine samples were analyzed for cadmium (Cd-B and Cd-U) by graphite-furnace atomic absorption spectrometry, and urine samples were analyzed also for alpha 1-microglobulin (alpha 1-MG-U), beta 2-microglobulin (beta 2-MG-U) and N-acetyl-beta-D-glucosaminidase (NAG-U) by conventional methods, all under strict quality control. The results were subjected to statistical analysis to examine the extents of biological variations through-out the study periods. RESULTS: Variations in geometric means (GMs) for Cd-B, Cd-U, alpha 1-MG-U, beta 2-MG-U, and NAG-U were all small; the ratio of the largest GM over the lowest GM was 1.1 for Cd-B, 2 for Cd-U and 2 to 3 for alpha 1-MG-U, beta 2-MG-U, and NAG-U in the 12-month survey, and 1.7 at largest for all parameters in the 10-week survey. The within-subject variations during the 12-month or 10-week periods were however large, i.e., more than 4-5-fold difference between the smallest and the largest values obtained for the same subject. Effects of the correction for urine density to reduce the variations were limited. In contrast, within-subject variation in Cd-B was small with a ratio of 1.3. CONCLUSIONS: Variations in GM values for Cd-U, alpha 1-MG-U, beta 2-MG-U, and NAG-U at different time of sampling are small so that single measurement would be acceptable as far as the evaluation on a group basis is the study objective. Within-subject variations are wide however, the ratio of the largest value over the smallest value being 4-5 or more, irrespective of correction for urine density. Therefore, care should be practiced when evaluation on an individual basis is intended. Very low within-subject variation in Cd-B may suggest the advantage of Cd-B over Cd-U for individual evaluation among general populations if blood sampling is accepted.