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Background: Recent literature suggest the effect of maternal smoking on risk of hypertensive disorders in pregnancy (HDP) and preeclampsia may differ by ethnicity; however, studies on Asians are limited.Methods: We investigated the association of maternal smoking with HDP and preeclampsia using a common analysis protocol to analyze the association in six birth cohorts participating in a Japanese consortium of birth cohorts (JBiCC). Results were compared with-published results from cohorts not included in this consortium, and, where possible, we produced a meta-analysis including these studies.Results: Meta-analysis of four cohort studies including 28,219 participants produced an odds ratio (OR) of 1.24 (95% confidence interval [CI], 0.88–1.87) for the effect of smoking beyond early pregnancy compared to women who did not smoke during pregnancy. These results combined with those from the Japan Environment and Children’s Study (JECS) yielded an OR of 1.19 (95% CI, 1.00–1.43, P = 0.056). Meta-analysis results for categories of smoking volume were insignificant, but when combined with JECS yielded an OR of 0.86 (95% CI, 0.65–1.12) for smoking 1–4 cigarettes, 1.25 (95% CI, 0.98–1.60) for smoking 5–9 cigarettes, and 1.27 (95% CI, 1.04–1.54) for smoking 10 or more cigarettes per day. All effects were insignificant for preeclampsia.Conclusion: Our results suggest that the protective effects of smoking longer and smoking more on HDP and preeclampsia repeatedly observed among Europeans and North Americans likely do not hold for the Japanese.

Background The concept of health literacy has gained prominence in the context of oral health. In Japan, curative dental care is generally under universal health coverage, while preventive dental care requires effort. We used this situation to test the hypothesis that high health literacy is associated with preventive dental care use and good oral health status, but not with curative dental care use, in Japan. Methods A questionnaire survey was conducted from 2010 to 2011 among residents aged 25–50 years in Japanese metropolitan areas. Data from 3767 participants were used. Health literacy was measured using the Communicative and Critical Health Literacy Scale, and the total score was categorized into quartiles. Poisson regression analyses with robust variance estimators were conducted to examine the associations of health literacy with curative dental care use, preventive dental care use, and good oral health, adjusted for covariates. Results The percentages of curative dental care use, preventive dental care use, and good oral health were 40.2%, 28.8%, and 74.0%, respectively. Health literacy was not associated with curative dental care use; the prevalence ratio (PR) of the highest relative to the lowest quartile of health literacy was 1.04 (95% confidence interval [CI], 0.93–1.18). High health literacy was associated with preventive dental care use and good oral health; the corresponding PRs were 1.17 (95% CI, 1.00–1.36) and 1.09 (95% CI, 1.03–1.15), respectively. Conclusions These findings may provide clues for the design of effective interventions to promote preventive dental care use and improve oral health status.

Background: While a wide range of predictors of postpartum smoking relapse have been suggested, population-based studies have rarely examined these factors exclusively among women who quit in early pregnancy. Furthermore, workplace secondhand smoke (SHS) exposure has never been examined.Methods: We analyzed data from 10,466 pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Age, education, parity, breastfeeding, postpartum depression, SHS exposure at home, and SHS exposure at work (not working, working without SHS exposure, working with SHS exposure) were evaluated as possible predictors. Multiple logistic regression analyses were conducted to examine the associations between these factors and smoking relapse by 1 year postpartum among women who quit in early pregnancy. Analyses stratified by SHS exposure at home were also conducted.Results: About one-fourth of early-pregnancy quitters had relapsed into smoking by 1 year postpartum. Lower education, multiparity, not breastfeeding, postpartum depression, and SHS exposure at home were associated with increased risks of smoking relapse. Working with SHS exposure was associated with an increased risk of smoking relapse; the multivariate-adjusted odds ratios of working without SHS exposure and working with SHS exposure compared with not working were 1.14 (95% confidence interval [CI], 0.82–1.59) and 2.18 (95% CI, 1.37–3.46), respectively. The significant association of workplace SHS exposure was observed only among women without SHS exposure at home.Conclusion: SHS exposure at work, as well as education, multiparity, breastfeeding, postpartum depression, and SHS exposure at home were associated with postpartum smoking relapse among early-pregnancy quitters.

Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40–49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. Of 72 998 women enrolled, 36 859 were assigned to the intervention group and 36 139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2–95·0 vs 77·0%, 70·3–83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3–88·0 vs 91·4%, 91·1–91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034). Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. Ministry of Health, Labour and Welfare of Japan.

Background: More research is needed to clarify the health effects of dietary carotenoid intakes, and this requires the use of high-quality assessments of habitual dietary intake. Cohort studies from the Tohoku Medical Megabank Organization included a self-administered food frequency questionnaire (TMM-FFQ) for community-dwelling adults. This study evaluated the validity of carotenoid intakes derived from the TMM-FFQ using serum carotenoid concentrations as the gold standard.Methods: In Miyagi Prefecture, 88 men and 124 women aged ≥20 years voluntarily agreed to participate in the study and provided completed TMM-FFQs and blood samples in 2019 and 2021. Carotenoids examined included α-carotene, β-carotene, β-cryptoxanthin, and lycopene. Intraclass correlation coefficients (ICCs) were calculated to assess correlations between serum concentrations in 2019 and 2021. Spearman’s rank correlation coefficients were calculated to evaluate the correlations between energy-adjusted dietary carotenoid intakes from the TMM-FFQ in 2021 and the average serum carotenoid concentrations in 2019 and 2021, with correction for the attenuating effect of random within-individual variation.Results: The ICCs between serum concentrations over the 2 years were >0.50 for all carotenoids. Among men, correlation coefficients were 0.33 for α-carotene, 0.42 for β-carotene, 0.50 for β-cryptoxanthin, and −0.09 for lycopene. Among women, the coefficients were lower than those for men, except for lycopene: 0.11 for α-carotene, 0.23 for β-carotene, 0.21 for β-cryptoxanthin, and 0.28 for lycopene.Conclusion: The TMM-FFQ demonstrated reasonable validity for assessing intakes of α-carotene, β-carotene, and β-cryptoxanthin among men, but not among women, in the TMM cohort studies when using serum concentrations as the gold standard.

Background: The Tohoku Medical Megabank Project has initiated the Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study) including genomic and omics investigations and conducted a self-administered food frequency questionnaire with the response option “constitutionally unable to eat or drink it” for individual food items (TMM-FFQ) for pregnant women. This study evaluated the validity of the TMM-FFQ among pregnant women.Methods: Participants comprised 122 pregnant women aged ≥20 years residing in Miyagi Prefecture who completed weighed food records (WFRs) for 3 days as reference intake and the TMM-FFQ during mid-pregnancy. Correlations between nutrient or food group intakes based on the WFR and the TMM-FFQ were calculated using Spearman’s rank correlation coefficients (CCs), adjusting for energy intake and correcting for random within-individual variation of WFR. Cross-classification was also conducted according to quintiles using the WFR and TMM-FFQ data.Results: The percentages of participants who chose the “constitutionally unable to eat or drink it” option were >3% for seven food and drink items. CCs were >0.30 for 31 nutrients; the median across energy and 44 nutrients was 0.41. CCs were >0.30 for 14 food groups; the median across 20 food groups was 0.35. The median percentages of cross-classification into exact plus adjacent quintiles and extreme quintiles were 63.1% and 3.3% for energy and nutrients and 61.9% and 4.1% for food groups, respectively.Conclusion: The validity of the TMM-FFQ compared with the WFR was reasonable for certain nutrients and food groups among pregnant women in the TMM BirThree Cohort Study.

The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first large-scale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.Population genetics: large database of Japanese gene variations constructedA new database provides information on the frequency of genetic variations within 3552 Japanese individuals, and facilitates comparisons with other populations. The reference panel, constructed by Kengo Kinoshita of Tohoku University, Sendai, and colleagues in Japan is also the first large-scale database to provide genetic variation frequency information on the X chromosome and mitochondrial DNA in the Japanese population. The methods used to sequence the genetic data are similar to those used in other large databases, allowing comparisons with other populations. The population size and methods used to compile the database overcome limitations in previous Japanese reference panels. This and similar databases that catalog genetic variations within populations can improve efforts towards personalizing healthcare and contribute to the study of human population genetics. The database is publicly available online.

The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies. The Tohoku Medical Megabank Organization establishes a biobank with detailed patient health care and genome information. Here the authors analyse whole-genome sequences of 1,070 Japanese individuals, allowing them to catalogue 21 million single-nucleotide variants including 12 million novel ones.

Purpose The purpose of this study was to determine the ideal coronal alignment under dynamic conditions after open-wedge high tibial osteotomy (OWHTO). It was hypothesised that, although the classical target alignment was based on experimental evidence, it would demonstrate biomechanical validity. Methods Musculoskeletal computer models were analysed with various degrees of coronal correction in OWHTO during gait and squat, specifically with the mechanical axis passing through points at 40%, 50%, 60%, 62.5%, 70%, and 80% of the tibial plateau from the medial edge, defined as the weight-bearing line percentage (WBL%). The peak load on the lateral tibiofemoral (TF) joint, the medial collateral ligament (MCL), and anterior cruciate ligament (ACL) tensions, and knee kinematics with or without increased posterior tibial slope (PTS) were evaluated. Results The classical alignment with WBL62.5% achieved sufficient load on the lateral TF joint and maintained normal knee kinematics after OWHTO. However, over-correction with WBL80% caused an excessive lateral load and non-physiological kinematics. Increased WBL% resulted in increased MCL tension due to lateral femoral movement against the tibia. With WBL80%, abnormal contact between the medial femoral condyle and the medial intercondylar eminence of the tibia occurred at knee extension. The screw-home movement around knee extension and the TF rotational angle during flexion were reduced as WBL% increased. Increased PTS was associated with increased ACL tension and decreased TF rotation angle because of ligamentous imbalance. Conclusions The classical target alignment demonstrated validity in OWHTO, and over-correction should be avoided as it negatively impacts clinical outcome. Level of evidence IV.