Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study.

BACKGROUND: Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce. METHODS: We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p < 5.0 × 10- 8) in the discovery stage were selected for genotyping in the replication stage. A meta-analysis integrating the discovery and replication stage results (n = 19,515) was conducted. NVP-related variables were identified as categorical or continuous. RESULTS: GWAS analysis in the discovery phase revealed loci linked to NVP in two gene regions, 11q22.1 (rs77775955) and 19p13.11 (rs749451 and rs28568614). Loci in these two gene regions have also been shown to be associated with HG in a White European population, indicating the generalizability of the GWAS analyses conducted in this study. Of these, only rs749451 and rs28568614 at 19p13.11 reached the genome-wide suggestive level (p < 1.0 × 10- 5) in the replication stage; however, both loci were significant in the meta-analysis. CONCLUSIONS: NVP-related loci were identified in the Japanese population at 11q22.1 and 19p13.11, as reported in previous GWAS. This study contributes new evidence on the generalizability of previous GWAS on the association between genetic background and NVP.

Maternal social isolation and behavioral problems in preschool children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

It is essential to clarify factors associated with mental health and behavioral problems in early childhood, because children are critical stages of life for mental health. We aimed to prospectively examine the associations between maternal social isolation and behavioral problems in preschool children. We analyzed data from 5842 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores < 12) one year after delivery. The Child Behavior Checklist 1½-5 was used to assess behavioral problems, and its subscales were used to assess internalizing and externalizing problems in children at 4 years of age. Multiple logistic regression analyses were conducted to examine the associations between social isolation and behavioral problems, after adjustment for age, education, income, work status, marital status, extraversion, neuroticism, depressive symptoms, child sex, and number of siblings. Multiple logistic regression analyses were also conducted for internalizing problems and externalizing problems. The prevalence of maternal social isolation was 25.4%. Maternal social isolation was associated with an increased risk of behavioral problems in children: the odds ratio (OR) was 1.37 (95% confidence interval [CI] 1.14-1.64). Maternal social isolation was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.33 (95% CI, 1.12-1.59) and 1.40 (95% CI, 1.18-1.66), respectively. In conclusion, maternal social isolation one year after delivery was associated with behavioral problems in children at 4 years of age.

Association between frequency of breakfast intake before and during pregnancy and developmental delays in children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Although an association between maternal nutritional intake and developmental delays in children has been demonstrated, the association of the timing of meal intake and development delays remains unclear. We examined the association between breakfast intake frequency before and during pregnancy and developmental delay in children. METHODS: Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 7491 answered the required questions and were analyzed. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: daily, and 5-6, 3-4, and 0-2 times/week. Child developmental delays at age 2 and 3.5 years were assessed using the Ages & Stages Questionnaire, Third Edition. Logistic regression models were constructed to examine the association between breakfast intake frequency in pregnant women and developmental delays in children aged 2 and 3.5 years. RESULTS: The proportion of pregnant women who had breakfast daily was 78.1% in pre- to early pregnancy, and 82.2% in early to mid-pregnancy. The proportion of children with developmental delays was 14.7% and 13.4% at age 2 and 3.5 years, respectively. Compared with the risk in children of women who had breakfast daily from pre- to early pregnancy, children of women who had breakfast 0-2 times/week had a higher risk of developmental delays at 2 years of age: odds ratio (OR) 1.30, (95% confidence interval [CI], 1.02-1.66). The risk of developmental delays at age 2 years increased in the children of women who had breakfast 0-2 times/week in early to mid- pregnancy: OR 1.75 (95% CI, 1.32-2.32). The risk of developmental delays at age 3.5 years did not increase in the children of women who had breakfast 0-2 times/week from pre- to early and early to mid-pregnancy: OR 1.06 (95% CI, 0.81-1.39 and OR 1.15 (95% CI 0.84-1.57), respectively. CONCLUSION: For women with a low frequency of breakfast intake from pre- to mid-pregnancy there was an association with developmental delays in their children at age 2, but not at 3.5 years.

Association between frequency of breakfast intake before and during pregnancy and infant birth weight: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Low birth weight is associated with an increased risk of developing chronic diseases in adulthood, with a particularly high incidence in Japan among developed countries. Maternal undernutrition is a risk factor for low birth weight, but the association between the timing of food intake and infant birth weight has not been investigated. This study aimed to examine the association between breakfast intake frequency among Japanese pregnant women and infant birth weight. METHODS: Of all pregnant women who participated in the Tohoku Medical Megabank Project Three Generation Cohort Study, 16,820 who answered the required questions were included in the analysis. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: every day and 5-6, 3-4, and 0-2 times/week. Multivariate linear regression models were constructed to examine the association between breakfast intake frequency among pregnant women and infant birth weight. RESULTS: The percentage of pregnant women who consumed breakfast daily was 74% in the pre- to early pregnancy period and 79% in the early to mid-pregnancy period. The average infant birth weight was 3,071 g. Compared to women who had breakfast daily from pre- to early pregnancy, those who had breakfast 0-2 times/week had lower infant birth weight (ß = -38.2, 95% confidence interval [CI]: -56.5, -20.0). Similarly, compared to women who had breakfast daily from early to mid-pregnancy, those who had breakfast 0-2 times/week had lower infant birth weight (ß = -41.5, 95% CI: -63.3, -19.6). CONCLUSIONS: Less frequent breakfast intake before and mid-pregnancy was associated with lower infant birth weight.

Associations between sugar-sweetened beverages before and during pregnancy and offspring overweight/obesity in Japanese women: the TMM BirThree Cohort Study.

OBJECTIVE: The association between high sugar-sweetened beverages (SSB) intake during pregnancy and offspring overweight/obesity has been reported only from Western countries. The objective of this study was to examine the association between SSB intake before and during pregnancy and offspring overweight/obesity among Japanese women. DESIGN: Japanese prospective birth cohort study. SETTING: We analysed mother-offspring pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SSB intake during pregnancy was evaluated using the FFQ and classified into three groups: none (0 g/d), medium (<195 g/d) and high (>195 g/d). Overweight or obesity at 1 year of age in offspring was defined as having a BMI Z-score greater than 2 sd, calculated based on the BMI reference data for Japanese children. Multiple logistic regression analyses were performed to examine the associations between SSB intake before and during pregnancy and offspring overweight/obesity, after adjusting for covariates. PARTICIPANTS: Japanese mother-offspring pairs (n 7114). RESULTS: The overweight/obesity rate of the offspring was 8·8 %. Pregnant women with a high intake of SSB in early to mid-pregnancy had a higher risk of overweight/obesity in their offspring compared with those who did not; the OR was 1·52 (95 % CI (1·09, 2·12)). CONCLUSIONS: High SSB intake in early to mid-pregnancy was associated with an increased risk of offspring overweight/obesity at 1 year of age.

Association between maternal psychological distress and children's neurodevelopment in offspring aged 4 years in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

AIM: An association between maternal psychological distress and children's development has been reported, but  reports from Japan are limited. This study aimed to examine the association of maternal psychological distress with children's neurodevelopment in Japan. METHODS: The study assessed data of 7646 mother-infant pairs in the Japanese population. We used Kessler Psychological Distress Scale, a screening tool for psychological distress, to assess maternal psychological distress in early pregnancy and 2 years postpartum and divided it into four categories: none in both the pre-natal and post-natal periods, only the pre-natal period, only the post-natal period and both the pre-natal and post-natal periods. Children's neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition (ASQ-3) at 4 years of age. ASQ-3 comprises five domains (communication, gross motor, fine motor, problem solving and personal-social), and the score of less than -2 standard deviation relative to the mean in reference was defined as having developmental delay. We conducted multivariate logistic regression analysis to examine the association between maternal psychological distress and children's neurodevelopment. RESULTS: The prevalence of developmental delay of communication, gross motor, fine motor, problem solving and personal-social were 4.0%, 4.3%, 4.9%, 3.8% and 4.6%, respectively. Maternal psychological distress in only the postpartum period and both pre-natal and postpartum periods were associated with risks of developmental delay in all domains. Maternal psychological distress in only the pre-natal period was associated with developmental delay in communication. CONCLUSIONS: Maternal psychological distress is associated with risks of children's developmental delay.

Association of maternal psychological distress and the use of childcare facilities with children's behavioral problems: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Childcare facilities are a factor that lowers the established association of mother's postnatal psychiatric symptoms with children's behavioral problems. However, no studies have considered the prenatal psychiatric symptoms yet. This study examined whether the use of childcare facilities moderates the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years. METHODS: The present study was based on the data from 23,130 mother-child pairs participating in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. K6 was used to classify maternal psychological distress in early pregnancy and at two years postpartum into four categories: none in both prenatal and postnatal periods (none), only the prenatal period (prenatal only); only the postnatal period (postnatal only); both prenatal and postnatal periods (both). The children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½-5 (CBCL) aged four years. The clinical range of the externalizing, internalizing, and total problem scales of the CBCL was defined as having behavioral problems. To examine whether availing childcare facilities moderates the association between maternal psychological distress and children's behavioral problems, we conducted a stratified analysis based on the use of childcare facilities or not, at two years of age. The interaction term between maternal psychological distress and use of childcare facilities was included as a covariate in the multivariate logistic regression analysis to confirm the p-value for the interaction. RESULTS: The prevalence of the clinical ranges of externalizing problems, internalizing problems, and clinical range of total problems were 13.7%, 15.4%, and 5.8%, respectively. The association of maternal psychological distress with a high risk of children's behavioral problems was significant; however, the association between prenatal only psychological distress and externalizing problems in the group that did not use childcare facilities was not significant. Interactions between the use of childcare facilities and maternal psychological distress on behavioral problems in children were not significant. CONCLUSIONS: Use of childcare facilities did not moderate the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years.

Skipping breakfast during pregnancy and hypertensive disorders of pregnancy in Japanese women: the Tohoku medical megabank project birth and three-generation cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) adversely affect the prognosis of mother and child, and the prognosis depends on the subtype of HDP. Skipping breakfast may be associated with increased blood pressure due to disruption of the circadian clock, but the association with the development of HDP has not been studied. The purpose of this study was to examine the association between skipping breakfast and the development of HDP and HDP subtypes in Japanese pregnant women. METHODS: Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 18,839 who answered the required questions were included in the analysis. This study had a cross-sectional design. The breakfast intake frequency from pre-pregnancy to early pregnancy was classified into four groups: daily, 5-6 times per week, 3-4 times per week, and 0-2 times per week. HDP was classified into gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and severe preeclampsia (SuPE). Multiple logistic regression analysis and multinomial logistic analysis were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breakfast intake frequency and development of HDP or HDP subtypes. We performed a stratified analysis based on energy intake. RESULTS: Of the participants, 74.3% consumed breakfast daily, and 11.1% developed HDP. Women who consumed breakfast 0-2 times per week had a higher risk of HDP (OR: 1.33, 95% CI: 1.14-1.56), CH (OR: 1.63, 95% CI: 1.21-2.19), and PE (OR: 1.68, 95% CI: 1.27-2.21) than those who consumed breakfast daily. No association was found between skipping breakfast and the risk of developing GH (OR: 1.26, 95% CI: 0.99-1.61) and SuPE (OR: 0.91, 95% CI: 0.55-1.49). Stratified analysis showed that the risk of developing HDP due to skipping breakfast was highest in the group with the highest daily energy intake. CONCLUSIONS: Skipping breakfast during pre-to early pregnancy is associated with the development of HDP. Further longitudinal studies are required to clarify the causal association between skipping breakfast and HDP.

Dietary patterns before and during pregnancy and small for gestational age in Japan: a prospective birth cohort study.

BACKGROUND: Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population. METHODS: Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively. RESULTS: A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed. CONCLUSIONS: The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.

Common carotid arteritis and polymyalgia with Mycoplasma pneumoniae infection.

A few pediatric cases with brain vasculitis most frequently affecting the middle cerebral artery have been reported in association with Mycoplasma pneumoniae infection, but involvement of the common carotid artery (CCA) before the bifurcation has not been reported to date. We report herein a case of 10-year-old boy with common carotid arteritis and polymyalgia associated with Mycoplasma pneumoniae infection. His fever and cough began 2 weeks before, and his right upper and lower extremity pains began 2 days before admission. He had initially been treated with clarithromycin followed by tosufloxacin, but his symptoms persisted. His M. pneumonia-specific antibody titer was high on admission (1:10240 by particle agglutination method) and the gene of M. pneumoniae was detected in a throat swab specimen by the loop-mediated isothermal amplification method with initial high levels of serum interleukin-8, tumor necrosis factor-α, and interleukin-18 along with elevated blood levels of complements. On the 5th day of hospitalization, vascular echograms of the extremities and neck showed increasing intima-media thickness of bilateral CCAs without stenosis and/or thrombosis and T2-weighted with lipid suppression magnetic resonance imaging of the neck showed high signal intensity of bilateral CCA walls. Coagulation studies were unremarkable and no autoantibodies were detected as far as tested. He was successfully treated by intravenous administration of prednisolone and was stable without any neurological sequelae 17 months after the onset without medication. His particle agglutination titer decreased to 1:5120, and serum interleukin-8, tumor necrosis factor-α, interleukin-18, and complement levels returned to normal.

Intravital phosphorescence lifetime imaging of the renal cortex accurately measures renal hypoxia.

Renal tubulointerstitial hypoxia is recognized as a final common pathway of chronic kidney disease and is considered a promising drug target. However, hypoxia in the tubules is not well examined because of limited detection methods. Here, we devised a method to visualize renal tubular oxygen tension with spatial resolution at a cellular level using the cell-penetrating phosphorescent probe, BTPDM1 (an iridium-based cationic lipophilic dye), and confocal phosphorescence lifetime imaging microscopy to precisely assess renal hypoxia. Imaging with BTPDM1 revealed an oxygen gradient between S1 and S2 segments in mouse kidney. We also demonstrated that our microscopy system can detect subtle changes of hypoxemia and reoxygenation, and the acquired phosphorescence lifetime can be converted to partial pressure of oxygen. This new method allows, for the first time, visualization of intravital oxygen gradients at the renal surface with high spatial resolution. Thus, the confocal phosphorescence lifetime imaging microscopy platform, combined with BTPDM1, will promote an accurate understanding of tissue hypoxia, including renal hypoxia.

Long-term outcome of stereotactic body radiotherapy for patients with small hepatocellular carcinoma.

AIM: To evaluate the long-term outcome of stereotactic body radiotherapy in patients with small hepatocellular carcinoma who were ineligible for resection or ablation therapies. METHODS: A total of 65 patients with 74 hepatocellular carcinomas (median tumor size 16 mm) were enrolled in the present study. They were treated with the prescribed dose of 48 Gy in four fractions at the isocenter. We extended the observation period and analyzed long-term outcomes, including overall survival, progression-free survival, local control, and various prognostic factors, in these patients. RESULTS: The median follow-up period was 41 months for all patients and 62 months for surviving patients. The 3- and 5-year overall survival rates were 56.3% (95% confidence interval, 44.1-68.5%) and 41.4% (95% confidence interval, 28.7-54.1%), respectively. The 3- and 5-year progression-free survival rates were 25.4% (95% confidence interval, 14.0-36.8%) and 10.6% (95% confidence interval, 1.5-19.8%), respectively. The 3- and 5-year local control rates were both 100% (95% confidence interval 100%). Liver toxicities exceeding grade 3 were observed in 15 patients (23.1%). The proportion of patients who had grade ≥3 toxicities did not increase. Adverse effects (grade ≤2) presented as significant prognostic factors of overall survival, while TNM stage (T1N0M0) was a significant prognostic factor of progression-free survival after multivariate analysis. CONCLUSIONS: Stereotactic body radiotherapy was effective for patients with small hepatocellular carcinomas who were ineligible for resection or ablation therapies. The incidence of grade ≥3 adverse effects did not increase, even after longer follow-up times.

Simultaneous site-directed mutagenesis of duplicated loci in soybean using a single guide RNA.

KEY MESSAGE: Using a gRNA and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two GmPPD loci in soybean. Mutations in GmPPD loci were confirmed in at least 33% of T2 seeds. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9 (Cas9) system is a powerful tool for site-directed mutagenesis in crops. Using a single guide RNA (gRNA) and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two homoeologous loci in soybean (Glycine max), GmPPD1 and GmPPD2, which encode the orthologs of Arabidopsis thaliana PEAPOD (PPD). Most of the T1 plants had heterozygous and/or chimeric mutations for the targeted loci. The sequencing analysis of T1 and T2 generations indicates that putative mutation induced in the T0 plant is transmitted to the T1 generation. The inheritable mutation induced in the T1 plant was also detected. This result indicates that continuous induction of mutations during T1 plant development increases the occurrence of mutations in germ cells, which ensures the transmission of mutations to the next generation. Simultaneous site-directed mutagenesis in both GmPPD loci was confirmed in at least 33% of T2 seeds examined. Approximately 19% of double mutants did not contain the Cas9/gRNA expression construct. Double mutants with frameshift mutations in both GmPPD1 and GmPPD2 had dome-shaped trifoliate leaves, extremely twisted pods, and produced few seeds. Taken together, our data indicate that continuous induction of mutations in the whole plant and advancing generations of transgenic plants enable efficient simultaneous site-directed mutagenesis in duplicated loci in soybean.

Irritable bowel syndrome and quality of life in a community-dwelling population in Japan.

Objective Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and is characterized by recurrent abdominal pain or abnormal defecation. This investigation evaluated the relationship between IBS and self-reported quality of life in a community-dwelling population in Japan. Methods For this cross-sectional survey, we enrolled 1002 volunteers who participated in the Iwaki Health Promotion Project in 2013. IBS symptoms were evaluated using the criteria from the Japanese version of the Rome III Questionnaire. The assessments included an interview to obtain sociodemographic data, the second version of the Short-Form Health Survey (SF-36), and the Center for Epidemiologic Studies Depression Scale. Multiple regression analysis was used to assess the relationship between IBS symptoms and scores on the SF-36. Results A total of 59 subjects (5.9%) were classified as having IBS. Scores for all eight domains of the SF-36, the physical component summary, and the mental component summary were significantly and negatively associated with the Center for Epidemiologic Studies Depression scores. Physical functioning, role physical, vitality, mental health, and physical component summary scores were significantly and negatively associated with IBS. Conclusions The burden of IBS symptoms affects both physical and mental wellbeing, even after adjusting for confounders. Our findings suggest that screening for IBS symptoms and evaluating the need for medical care is important for community health workers.

Serum pentosidine concentration is associated with radiographic severity of lumbar spondylosis in a general Japanese population.

The aim of this study was to investigate the relationship between the radiographic severity of lumbar spondylosis (LS) and serum bone metabolic markers. A total of 681 individuals volunteered for this study (269 men, 412 women; age: 54.9 ± 14.3; body mass index [BMI]: 23.1 ± 3.3 kg/m2). Lateral lumbar radiographs were evaluated in each intervertebral section (L1/2 to L5/S1) using the Kellgren-Lawrence grade (KL). If at least one intervertebral section was graded as KL 2 or greater, the participants were considered to have LS. The summation of each section of intervertebral section was used as the radiographic severity value of LS. In addition, bone status was evaluated with an osteo-sono assessment index (OSI) at the calcaneus. Serum bone alkaline phosphatase (µg/mL), N-telopeptide of type I collagen (nMBCE/L), and pentosidine (pmol/mL) concentrations were examined and used as the bone metabolism index. Stepwise multiple linear regression analysis was conducted with the radiographic severity value of LS as the dependent variable and age, sex, BMI, OSI, and the value of serum bone metabolic markers as the independent variables. The total number of LS participants was 470 (69.0 %); the frequency of LS was higher in men (n = 198) than in women (n = 272; P = 0.036, χ 2 test). The mean severity value of LS was 7.1 ± 4.4, and the mean value of pentosidine was 120.7 ± 54.8 pmol/mL. On multiple regression analysis, age (B = 0.190, ß = 0.611), sex (men = 1, women = 2; B = -0.900, ß = -0.099), BMI (B = 0.185, ß = 0.136), and pentosidine (B = 0.009, ß = 0.115) were significantly correlated with the severity of LS. Serum pentosidine concentration was positively correlated with the radiographic severity of LS in this cross-sectional study.

Clinical relevance of aortic calcification in urolithiasis patients.

BACKGROUND: The aim of the present study is to investigate the clinical relevance of aortic calcification in urolithiasis patients. METHODS: Between January 2010 and September 2014, 1221 patients with urolithiasis were treated in Oyokyo Kidney Research Institute and Hirosaki University Hospital. Among these, 287 patients (Stone group) on whom adequate data were available were included in this retrospective study. We also selected 148 subjects with early stage (pT1N0M0) renal cell carcinoma from 607 renal cell carcinoma patients who underwent radical nephrectomy at Hirosaki University Hospital (Non-stone group) as control subjects. Validity of the Non-stone group was evaluated by comparison with pair-matched 296 volunteers from 1166 subjects who participated in the Iwaki Health Promotion Project in 2014. Thereafter, age, body mass index, aortic calcification index (ACI), renal function, serum uric acid concentrations, and comorbidities (diabetes, hypertension, or cardiovascular disease) were compared between the Non-stone and Stone groups. Independent factors for higher ACI and impaired renal function were assessed using multivariate logistic regression analysis. RESULTS: We confirmed relevance of Non-stone group patients as a control subject by comparing the pair-matched community-dwelling volunteers. Backgrounds of patients between the Non-stone and Stone groups were not significantly different except for the presence of hypertension in the Stone group. ACI was not significantly high in the Stone group compared with the Non-stone group. However, age-adjusted ACI was greater in the Stone group than the Non-stone group. Among urolithiasis patients, ACI was significantly higher in uric acid containing stone patients. The number of patients with stage 3B chronic kidney disease (CKD) was significantly higher in the Stone group than in the Non-stone group (12% vs. 4%, P = 0.008). Multivariate logistic regression analysis showed higher aortic calcification index (>13%), and being a stone former were independent factors for stage 3B CKD at the time of diagnosis. CONCLUSION: Aortic calcification and being a stone former had harmful influence on renal function. This study was registered as a clinical trial: UMIN: UMIN000022962.

Hypertensive disorders of pregnancy increase the risk for chronic kidney disease: A population-based retrospective study.

Hypertensive disorders of pregnancy (HDP) and chronic kidney disease (CKD) are well-known risk factors for cardiovascular disease (CVD) in later life. However, few studies have investigated the association of HDP with CKD. Moreover, these studies utilized either registry- or clinical-based data and did not include subclinical CKD patients. To address this gap in the literature, we investigated whether HDP is related to CKD, diagnosed based on the estimated glomerular filtration rate (eGFR), in later life. We designed a population-based, retrospective study, and reviewed the results of blood and physiological examinations as well as the results of pregnancy data available in patients' Maternity Health Record Books for 312 women. We identified 15 women with a diagnosis of CKD based on the eGFR, and 14 women with HDP. We found that women who experienced HDP had a high risk of CKD in later life compared with women without HDP (odds ratio (OR): 4.854; 95% confidence interval (CI): 1.042-22.621). Compared with normotensive women, those who were hypertensive at the time of the examination were significantly associated with CKD (OR: 3.109; 95% CI: 1.213-11.510). Awareness regarding the risk for CKD and CVD in a relatively young age can enable women to prevent diseases effectively.

Association of clinical and radiographic signs of femoroacetabular impingement in the general population.

BACKGROUND: The relationships between the clinical and radiographic signs of femoroacetabular impingement (FAI) are unknown. The purpose of this study was to assess the relationship between hip pain, a positive anterior impingement sign (AIS), and radiographic signs of FAI in a general Japanese population. METHODS: A total of 616 individuals participated in this study. Hip pain was assessed using the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) pain category score and the AIS was used as a provocation test. Participants were divided into a positive AIS group (at least one positive hip) and a negative AIS group. Radiographs were assessed for the cross-over sign (COS), ischial spine sign (ISS), posterior wall sign (PWS), and pistol grip deformity (PGD). Then, the relationships between the clinical and radiographic signs of FAI were evaluated. RESULTS: JHEQ pain scores did not differ between men and women. Seven men (3.4%) and 29 women (7.1%) had a least one hip with a positive AIS. The mean JHEQ pain scores were 22.9 ± 7.2 for the positive and 27.3 ± 2.2 for the negative AIS group (P < 0.01). The prevalences of COS, ISS, PWS, and PGD were 8.9%, 17.2%, 21.8%, and 1.9%, respectively. There were no significant associations between degree of hip pain, AIS, and each radiographic finding. CONCLUSIONS: Radiographic signs of FAI were not associated with the degree of hip pain or a positive AIS, which suggests that radiographic findings may not be important in the clinical diagnosis of FAI.

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas.

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained-from 339 healthy volunteers (HV)-controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.

Lumbar spondylosis, lumbar spinal stenosis, knee pain, back muscle strength are associated with the locomotive syndrome: Rural population study in Japan.

OBJECTIVES: To comprehensively investigate the clinical and physical factors associating with locomotive syndrome (Loc-S); the locomotorium-disability for daily life. METHODS: 647 volunteers participated (247 males, 400 females, Age: 58.4 ± 11.0, BMI: 22.5 ± 3.3). Three self-assessment questionnaires were administered: 1) "25-question Geriatric Locomotive Function Scale" (GFLS-25) for evaluating Loc-S (GLFS-25 ≥ 16 defined as Loc-S); 2) "diagnostic support tool for LSS" (LSS-DST) for evaluating the prevalence of lumbar spinal stenosis (LSS); 3) Knee injury and Osteoarthritis Outcome Score (KOOS). Plain radiographs of the bilateral knees and lumbar spine were evaluated, and the severity of lumbar spondylosis (LS) and knee osteoarthritis (KOA) defined by Kellgren-Lawrence grade. Bone status was evaluated by using the osteo-sono assessment index (OSI) at the calcaneus. Isometric muscle strength of trunk and leg (Nm/kg, both extension and flexion) were evaluated. Linear regression analysis was performed to elucidate the factors concerned with GFLS-25 including age, sex, and BMI. RESULTS: Thirty-nine subjects (6.0%, 13 males, 26 females) were defined as having Loc-S. Single regression model showed that age, height, BMI, skeletal muscle mass, OSI, LSS, KOOS, the severity of LS and KOA, and trunk- and leg-muscle strength were correlated with the degree of GLFS-25. Stepwise multiple regression model showed that sex, height, LSS, KOOS, the severity of LS, and back muscle strength were significantly correlated with that of GLFS-25. CONCLUSION: In this cross-sectional study, pain status associated with LSS and knee joint, structural severity for LS, and back muscle strength primarily affected the degree of GFLS-25. For managing Loc-S, we must pay more intensive attention to these factors.