A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

This global multicenter study on reference values (RVs) allowed us to explore biological sources of variation (SVs) of RVs across the world.As described in the first part of this paper, RVs of 50 major analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as partial correlation coefficient (rp).Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related change profiles of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromrp, BMI related changes were observed in many nutritional and inflammatory markers in almost all countries. However, the slope of linear BMI vs. RV relationship differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes.Features of sex, age, alcohol, and smoking-related changes in RVs of major analytes were almost comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases

Msx1のMH6ドメインを含むC末端領域は骨格形成に関与する

MSX1 is a causative gene for oligodontia in humans. Although conventional Msx1-deficient mice die neonatally, a mutant mouse lacking the C-terminus MH6 domain of MSX1 (Msx1ΔMH6/ΔMH6) showed two different phenotypes; newborn homozygotes with cleft palates died neonatally, whereas those with thin palates remained alive and had craniofacial dysplasia and growth retardation compared with wild-type mice, with most mice dying by the age of 4–5 weeks. In a previously reported case of human oligodontia caused by a heterozygous defect of the Msx1 MH6 domain, a small foramen was observed on the occipital bone. The aim of this study was to test the hypothesis that the Msx1 MH6 domain is involved in bone formation in vivo. In Msx1ΔMH6/ΔMH6 mice, cranial suture fusion was delayed at embryonic day 18.5, and the anteroposterior cranial diameter was smaller and long bone length was decreased at 3 weeks of age. The femoral epiphysis showed no change in the trabecular number, but decreased bone mass, bone density, and trabecular width in Msx1ΔMH6/ΔMH6 mice. In addition, cancellous bone mass was reduced and the cartilage layer in the growth plate was thinner in Msx1ΔMH6/ΔMH6 mice. The mRNA expression levels of major osteoblast and chondrocyte differentiation marker genes were decreased in Msx1ΔMH6/ΔMH6 mice compared with wild-type mice. These findings suggest that the C-terminal region including the MH6 domain of MSX1 plays important roles not only in tooth development and palatal fusion, but also in postnatal bone formation

cDNA cloning of rat proteasome subunit RC1, a homologue of RING10 located in the human MHC class II region

AbstractThe nucleotide sequence of a cDNA that encodes a new subunit, named RC1, of rat proteasomes (multicatalytic proteinase complexes) has been determined. The polypeptide predicted from the open reading frame consisted of 208 amino acid residues with a calculated molecular mass of 23,130, which is consistent with the size obtained by electrophoretic analysis of purified RC1. The partial amino acid sequences of several fragments of RC1, obtained by protein chemical analyses, were found to be in excellent accordance with those deduced from the cDNA sequence. Surprisingly, the overall structure of RC1 was found to be almost identical to that of recently isolated RING10, whose gene is located in the class II region of the human MHC gene cluster. This finding suggests that RC1 is a homologue of human RING10, supporting the proposal that proteasomes are involved in the antigen processing pathway

Management of Apert Syndrome

Aim and objective: To present an Apert syndrome patient with midfacial growth deficiency treated with Le Fort III distraction osteogenesis and subsequent two-jaw surgery. Background: Apert syndrome is expressed as a severe and irregular craniosynostosis, midfacial hypoplasia, and symmetric syndactyly in the fingers and toes. For craniosynostosis syndromes, treatment planning is complex due to the disharmony between facial profile and occlusion. Case description: A 4-year-and-5-month-old boy, diagnosed with Apert syndrome, showed a concave profile accompanied with midfacial hypoplasia, moderate exorbitism, a reversed occlusion of −10.0 mm, an anterior open bite of −5.0 mm, and skeletal class III jaw-base relationship. The patient, aged 15 years and 4 months, underwent a Le Fort III osteotomy, and subsequent osteodistraction was performed via a rigid external distraction (RED) device. His midfacial bone was advanced by approximately 7.0 mm. One year after the distraction, preoperative treatment with 0.018-in preadjusted edgewise appliances was initiated. Two-jaw surgery with a Le Fort I osteotomy and bilateral sagittal split ramus osteotomy was performed after 42 months of preoperative orthodontic treatment. At the age of 20 years and 9 months, his facial profile dramatically changed to a straight profile, and an acceptable occlusion with an adequate interincisal relationship was obtained. A functional occlusion with an excellent facial profile was maintained throughout the 2-year retention period, although the upper dental arch width was slightly decreased, resulting in the recurrence of the left posterior crossbite. Conclusion: Our report indicates the necessity of long-term follow-up in patients with craniosynostosis because of syndrome-specific growth and methodologically induced relapse. Clinical significance: The two-stage operation combining early distraction osteogenesis and postgrowth orthognathic surgery proves to be an effective therapy for correcting midfacial hypoplasia and skeletal mandibular protrusion caused by Apert syndrome

Cut-Off Value of Total Adiponectin

Aim To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml

永久歯の先天的欠如に関する臨床統計調査

永久歯の先天性欠如（以下，先欠とする）は，最も高頻度に発現する顎顔面領域の先天異常であり，様々な不正咬合を引き起こし，交換期における咬合誘導あるいは，永久歯列期における歯の排列に際して苦慮することが多い．しかし，歯科矯正用アンカースクリューの登場により，治療方針に多様性が生まれ，先欠を有する患者に対して，欠損部位・歯数に影響されない，顎顔面骨格形態に則した治療方針が選択できる症例が増加している．このような症例の治療計画を立案する際には，先欠が顎顔面骨格形態へ与える影響を明らかにしておく必要がある．そこで，今回我々は不正咬合患者における第三大臼歯を除く永久歯の先欠の実態把握，ならびに先欠が顎顔面骨格形態に及ぼす影響の解明を目的として臨床統計学的な検討を行った． 2011年4月から2016年3月までの5年間に不正咬合を主訴として徳島大学病院矯正歯科を受診した患者のうち，口唇裂・口蓋裂やその他の先天異常を有する患者，矯正歯科治療の既往を有する患者および先欠の確認が不可能であった患者を除外した653名（男性233名，女性420名）を対象とし，調査を行った．その結果，以下の所見を得た． 1．先欠を有する患者は96名（14.7％）であり，男女比は1.13：1と男性がやや多かった．1人あたりの先欠歯数としては，1歯のみの欠損が最も多く，49.0％を占めた． 2．歯種別発現頻度は，上下顎ともに第二小臼歯，側切歯の順で高かった． 3．先欠を有する患者を上顎先欠群，下顎先欠群，上下顎先欠群に分類し，比較検討を行ったところ，前歯部被蓋関係については，下顎先欠群においてoverjetが最も大きかった．顎骨の前後的位置関係については，下顎先欠群において∠ANBが大きく，∠SNBが小さくなる傾向を認め，上顎先欠群，上下顎先欠群では∠SNAが小さくなる傾向を認めた． 以上の所見より，先欠が顎顔面骨格の成長・発育に影響を及ぼす可能性が示されたことから，先欠に関連した顎顔面骨格形態の特徴を考慮した治療計画の立案が重要であることが示唆された

口唇裂・口蓋裂患者の歯数異常に関する調査

口唇裂・口蓋裂患者は，軟組織や骨の癒合不全だけでなく，永久歯の先天欠如や過剰などの歯数異常が認められ，歯科矯正学的対応に苦慮することも多い．そこで，口唇裂・口蓋裂患者における永久歯の歯数異常の実態を明らかにすることを目的として，1995年1月から2011年12月までの17年間に出生し，徳島大学病院矯正歯科を受診した口唇裂・口蓋裂患者（症候群を含まない）を対象とした調査を行い，以下の結果を得た． 1．調査資料が揃っている患者101名の男女比は，1：1.02であった． 2．顎裂保有者82名の顎裂部位は，1 ▼ 3の型が最も多く，次いで1 ▼23の型であった．（▼は顎裂部位を示す） 3．永久歯における歯数異常の発現率は63.4％であり，歯の欠如のみを有するものが50.5％，過剰歯のみを有するものは8.9％，歯の欠如と過剰歯をともに有するものは4.0％であった． 4．歯の欠如の歯種別頻度は，側切歯が最も多く，次いで第二小臼歯の順であった． 5．顎裂保有者のみを対象とすると，歯の欠如の発現頻度は披裂側で59.8％，非披裂側で24.3％であった． 以上のことから，口唇裂・口蓋裂患者での先天欠如歯の発現率は高いため，治療計画立案時に補綴治療を含めた包括的歯科治療の必要性が示唆された

Dietary diversity and healthy lifestyle

The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing and / or buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health

Fermented soy food and inflammatory makers

Epidemiological investigations have shown that consumption of soybeans or soy foods reduces the risk of the development of cardiovascular disease, cancer and osteoporosis. The aim of this study was to determine the associations between different soy foods and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers. The cross-sectional study included 1,426 Japanese workers (1,053 men and 373 women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated food frequency questionnaire. Associations of total soy foods, fermented soy food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels were examined by general linear model regression analysis. We found that total fermented soy food intake was inversely associated with multivariable-adjusted geometric concentration of IL-6 in men (Q1 : 1.03 pg/mL, Q5 : 0.94 pg/mL ; P for trend = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely associated with miso intake (β= -0.068 ; p = 0.034) and soy sauce intake in men (β= -0.074 ; p = 0.018). This study suggests that intake of total fermented soy food, miso and soy sauce be associated with IL-6 concentrations in Japanese men

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe