The reliability and validity of the Questionnaire - Children with Difficulties (QCD)

Background: The aim of this study was to evaluate the reliability and validity of the Questionnaire-Children with Difficulties (QCD), which was developed for the evaluation of children's daily life behaviors during specified periods of the day. Methods: The subjects were 1,514 Japanese public elementary and junior high school students. For the examination of reliability, Cronbach's alpha was calculated to assess the internal consistency of the questionnaire. With regard to validity, correlation coefficients were calculated to examine whether QCD scores correlated with those of the ADHD-Rating Scale (ADHD-RS) and the Oppositional Defiant Behavior Inventory (ODBI). Results: Cronbach's alpha coefficient for the total score of the QCD was .876. The correlation coefficients of the QCD score with ADHD-RS and ODBI scores were -.514 and -.577, respectively. Conclusions: The internal consistency and validity of the QCD were demonstrated. The QCD is a reliable and valid instrument for evaluating daily life problems for children during different time periods of the day.ArticleCHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH. 7:11 (2013)journal articl

Comparison of the Fixation Strengths of Screws between the Traditional Trajectory and the Single and Double Endplate Penetrating Screw Trajectories Using Osteoporotic Vertebral Body Models Based on the Finite Element Method

Study Design This is a finite element (FE) study. Purpose To compare the fixation strength of traditional trajectory (TT) and single and double endplate penetrating screw trajectories (SEPST/DEPST) to the osteoporotic vertebral body model based on the FE method. Overview of Literature SEPST/DEPST have been developed to enhance the fixation strength in patients with diffuse idiopathic hyperostosis (DISH). This technique was also applied to patients with osteoporosis. However, determining the superiority of SEPST/DEPST is difficult because of the heterogeneous patient backgrounds. Methods Twenty vertebrae (T12 and L1) from 10 patients with osteoporosis (two males and eight females; mean age, 74.7 years) were obtained to create the 10 FE models. First, a single screw was placed with TT and SEPST/DEPST, and the fixation strength was compared by axial pullout strength (POS) and multidirectional loading tests. Second, two screws were placed on the bilateral pedicles with TT and SEPST/DEPST, and the fixation force of the vertebrae in the constructs in flexion, extension, lateral flexion, and axial rotation was examined. Results SEPST and DEPST had 140% and 171% higher POS values than TT, respectively, and the DEPST result was statistically significant (p=0.007). The multidirectional fixation strength was significantly higher in DEPST and SEPST than in TT in the cranial, caudal, and medial directions (p<0.05) but not in the lateral direction (p=0.05). The vertebral fracture strength at the lower instrumented vertebra of the DEPST tended to be higher than that of TT. The vertebral motion angles in SEPST and DEPST were significantly smaller in lateral bending (p=0.02) and tended to be smaller in flexion and extension than in TT (p=0.13). Conclusions This study may provide useful information for spine surgeons in deciding whether to choose the SEPS or DEPS technique for augmenting fixation in osteoporotic vertebral fracture surgery

GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells

SummaryObjectiveThe role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway.MethodsThe vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter–enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA).ResultsERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter–enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells.ConclusionsCrosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration

Severe progressive scoliosis due to huge subcutaneous cavernous hemangioma: A case report

Cavernous hemangioma consists mainly of congenital vascular malformations present before birth and gradually increasing in size with skeletal growth. A small number of patients with cavernous hemangioma develop scoliosis, and surgical treatment for the scoliosis in such cases has not been reported to date. Here we report a 12-year-old male patient with severe progressive scoliosis due to a huge subcutaneous cavernous hemangioma, who underwent posterior correction and fusion surgery. Upon referral to our department, radiographs revealed a scoliosis of 85° at T6-L1 and a kyphosis of 58° at T4-T10. CT and MR images revealed a huge hemangioma extending from the subcutaneous region to the paraspinal muscles and the retroperitoneal space and invading the spinal canal. Posterior correction and fusion surgery using pedicle screws between T2 and L3 were performed. Massive hemorrhage from the hemangioma occurred during the surgery, with intraoperative blood loss reaching 2800 ml. The scoliosis was corrected to 59°, and the kyphosis to 45° after surgery. Seven hours after surgery, the patient suffered from hypovolemic shock and disseminated intravascular coagulation due to postoperative hemorrhage from the hemangioma. The patient developed sensory and conduction aphasia caused by cerebral hypoxia during the shock on the day of the surgery. At present, two years after the surgery, although the patient has completely recovered from the aphasia. This case illustrates that, in correction surgery for scoliosis due to huge subcutaneous cavernous hemangioma, intraoperative and postoperative intensive care for hemodynamics should be performed, since massive hemorrhage can occur during the postoperative period as well as the intraoperative period

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

Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation

Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2 occupancy at target sites in vivo.This study was funded by the Wellcome Trust (WT0834922 and WT081385), CRUK (C28585/A10839), NIHR, EMBO, Lister Institute of Preventative Medicine, RIKEN, MEXT, and JST CRES