Aging markers in human urine: A comprehensive, non‐targeted LC‐MS study

Metabolites in human biofluids document the physiological status of individuals. We conducted comprehensive, non‐targeted, non‐invasive metabolomic analysis of urine from 27 healthy human subjects, comprising 13 young adults (30 ± 3 years) and 14 seniors (76 ± 4 years). Quantitative analysis of 99 metabolites revealed 55 that displayed significant differences in abundance between the two groups. Forty‐four did not show a statistically significant relationship with age. These include 13 standard amino acids, 5 methylated, 4 acetylated, and 9 other amino acids, 6 nucleosides, nucleobases, and derivatives, 4 sugar derivatives, 5 sugar phosphates, 4 carnitines, 2 hydroxybutyrates, 1 choline, and 1 ethanolamine derivative, and glutathione disulfide. Abundances of 53 compounds decreased, while 2 (glutathione disulfide, myo‐inositol) increased in elderly people. The great majority of age‐linked markers were highly correlated with creatinine. In contrast, 44 other urinary metabolites, including urate, carnitine, hippurate, and betaine, were not age‐linked, neither declining nor increasing in elderly subjects. As metabolite profiles of urine and blood are quite different, age‐related information in urine offers additional valuable insights into aging mechanisms of endocrine system. Correlation analysis of urinary metabolites revealed distinctly inter‐related groups of compounds

Human age-declined saliva metabolic markers determined by LC–MS

Metabolites in human biofluids reflect individual physiological states influenced by various factors. Using liquid chromatography-mass spectrometry (LC–MS), we conducted non-targeted, non-invasive metabolomics using saliva of 27 healthy volunteers in Okinawa, comprising 13 young (30 ± 3 year) and 14 elderly (76 ± 4 year) subjects. Few studies have comprehensively identified age-dependent changes in salivary metabolites. Among 99 salivary metabolites, 21 were statistically age-related. All of the latter decline in abundance with advancing age, except ATP, which increased 1.96-fold in the elderly, possibly due to reduced ATP consumption. Fourteen age-linked and highly correlated compounds function in a metabolic network involving the pentose-phosphate pathway, glycolysis/gluconeogenesis, amino acids, and purines/pyrimidines nucleobases. The remaining seven less strongly correlated metabolites, include ATP, anti-oxidation-related glutathione disulfide, muscle-related acetyl-carnosine, N-methyl-histidine, creatinine, RNA-related dimethyl-xanthine and N-methyl-adenosine. In addition, glutamate and N-methyl-histidine are related to taste, so their decline suggests that the elderly lose some ability to taste. Reduced redox metabolism and muscle activity are suggested by changes in glutathione and acetyl-carnosine. These age-linked salivary metabolites together illuminate a metabolic network that reflects a decline of oral functions during human aging

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10−13; odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS

Congenital dislocation of the patella

Das Leben und Schreiben des weiblichen Religiosentums in der Devotio moderna stand im Mittelpunkt dieser literahistorischen Arbeit. Dreh- und Angelpunkt des Forschungsprojekts sind die aus den Frauengemeinschaften der spätmittelalterlichen Reformbewegung überlieferten Schwesternbücher des ausgehenden 15. und beginnenden 16. Jahrhunderts. Zie: Zusammenfassung.

Reliability and validity of a novel quality of life questionnaire for female patients with adolescent idiopathic scoliosis: Scoliosis Japanese Questionnaire-27: a multicenter, cross-sectional study

Abstract Background A progressive deformity associated with adolescent idiopathic scoliosis (AIS) negatively affects a patient’s health-related quality of life (HRQOL). Although the Scoliosis Research Society-22 (SRS-22) is the standard measurement tool for assessing HRQOL in patients with AIS, it is partially suboptimal for evaluating HRQOL in Japanese patients with AIS because of cultural differences. The purpose of this study was to develop a novel patient-reported outcome measure for Japanese female patients with AIS and to evaluate the reliability and validity of this questionnaire in comparison with the SRS-22 tool. Methods We developed 27 questions based on the psychosocial problems in the daily life of young female patients with AIS in Japan, the Scoliosis Japanese Questionnaire-27 (SJ-27). To evaluate its reliability, the internal consistency was assessed using Cronbach’s alpha coefficient. Concurrent validity was evaluated using Spearman’s correlation coefficient between the SJ-27 and the SRS-22. To investigate the construct validity of the SJ-27, the correlation between the SJ-27 questions was assessed using Akaike’s information criterion (AIC). Results We analyzed 384 female patients with AIS. Cronbach’s alpha coefficients were 0.914 and 0.829 for the SJ-27 and the SRS-22, respectively. Spearman’s correlation coefficient between the SJ-27 and the SRS-22 was 0.692 (p < 0.001). The AIC analysis indicated that the SJ-27 items are divided into five domains, indicating that the SJ-27 covered a wide range of health-related problems among female patients with AIS. Conclusions The results suggest that the SJ-27 is a reliable and valid patient-reported outcome measure for evaluating HRQOL in female patients with AIS in Japan