AC and AG Dinucleotide Repeats in the PAX6 P1 Promoter are Associated with High Myopia

Purpose: The PAX6 gene, located at the reported myopia locus MYP7 on chromosome 11p13, was postulated to be associated with myopia development. This study investigated the association of PAX6 with high myopia in 379 high myopia patients and 349 controls. Methods: High myopia patients had refractive errors of –6.00 diopters or greater and axial length longer than 26 mm. Control subjects had refractive errors less than –1.00 diopter and axial length shorter than 24 mm. The P1 promoter, all coding sequences, and adjacent splice-site regions of the PAX6 gene were screened in all study subjects by polymerase chain reaction and direct sequencing. PAX6 P1 promoter-luciferase constructs with variable AC and AG repeat lengths were prepared and transfected into human ARPE-19 cells prior to assaying for their transcriptional activities. Results: No sequence alterations in the coding or splicing regions showed an association with high myopia. Two dinucleotide repeats, (AC)m and (AG)n, in the P1 promoter region were found to be highly polymorphic and significantly associated with high myopia. Higher repeat numbers were observed in high myopia patients for both (AC)m (empirical p = 0.013) and (AG)n (empirical p = 0.012) dinucleotide polymorphisms, with a 1.327-fold increased risk associated with the (AG)n repeat (empirical p = 0.016; 95% confidence interval: 1.059–1.663). Luciferase-reporter analysis showed elevated transcription activity with increasing individual (AC)m and (AG)n and combined (AC)m(AG)n repeat lengths. Conclusions: Our results revealed an association between high myopia and AC and AG dinucleotide repeat lengths in the PAX6 P1 promoter, indicating the involvement of PAX6 in the pathogenesis of high myopia

Dynamic magnetic resonance imaging in assessing lung function in adolescent idiopathic scoliosis: a pilot study of comparison before and after posterior spinal fusion

<p>Abstract</p> <p>Background</p> <p>Restrictive impairment is the commonest reported pulmonary deficit in AIS, which improves following surgical operation. However, exact mechanism of how improvement is brought about is unknown. Dynamic fast breath-hold (BH)-MR imaging is a recent advance which provides direct quantitative visual assessment of pulmonary function. By using above technique, change in lung volume, chest wall and diaphragmatic motion in AIS patients before and six months after posterior spinal fusion surgery were measured.</p> <p>Methods</p> <p>16 patients with severe right-sided predominant thoracic scoliosis (standing Cobb's angle 50° -82°, mean 60°) received posterior spinal fusion without thoracoplasty were recruited into this study. BH-MR sequences were used to obtain coronal images of the whole chest during full inspiration and expiration. The following measurements were assessed: (1) inspiratory, expiratory and change in lung volume; (2) change in anteroposterior (AP) and transverse (TS) diameter of the chest wall at two levels: carina and apex (3) change in diaphragmatic heights. The changes in parameters before and after operation were compared using Wilcoxon signed ranks test. Patients were also asked to score their breathing effort before and after operation using a scale of 1–9 with ascending order of effort. The degree of spinal surgical correction at three planes was also assessed by reformatted MR images and correction rate of Cobb's angle was calculated.</p> <p>Results</p> <p>The individual or total inspiratory and expiratory volume showed slight but insignificant increase after operation. There was significantly increase in bilateral TS chest wall movement at carina level and increase in bilateral diaphragmatic movements between inspiration and expiration. The AP chest wall movements, however, did not significantly change.</p> <p>The median breathing effort after operation was lower than that before operation (p < 0.05).</p> <p>There was significant reduction in coronal Cobb's angle after operation but the change in sagittal and axial angle at scoliosis apex was not significant.</p> <p>Conclusion</p> <p>There is improvement of lateral chest wall and diaphragmatic motions in AIS patients six months after posterior spinal fusion, associated with subjective symptomatic improvement. Lung volumes however, do not significantly change after operation. BH-MR is novel non-invasive method for long term post operative assessment of pulmonary function in AIS patients.</p

Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis

IntroductionAdolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case–control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS.MethodsThe study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle &lt;6°). Clinical and radiological assessments were conducted on each group.ResultsCobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p &lt; 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011).DiscussionPatients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression

Monitoring of Curve Progression in Patients with Adolescent Idiopathic Scoliosis Using 3-D Ultrasound

Objective: The aim of the work described here was to determine whether 3-D ultrasound can provide results comparable to those of conventional X-ray examination in assessing curve progression in patients with adolescent idiopathic scoliosis (AIS). Methods: One hundred thirty-six participants with AIS (42 males and 94 females; age range: 10–18 y, mean age: 14.1 ± 1.9 y) with scoliosis of different severity (Cobb angle range: 10º– 85º, mean: of 24.3 ± 14.4º) were included. Each participant underwent biplanar low-dose X-ray EOS and 3-D ultrasound system scanning with the same posture on the same date. Participants underwent the second assessment at routine clinical follow-up. Manual measurements of scoliotic curvature on ultrasound coronal projection images and posterior–anterior radiographs were expressed as the ultrasound curve angle (UCA) and radiographic Cobb angle (RCA), respectively. RCA and UCA increments ≥5º represented a scoliosis progression detected by X-ray assessment and 3-D ultrasound assessment, respectively. Results: The sensitivity and specificity of UCA measurement in detecting scoliosis progression were 0.93 and 0.90, respectively. The negative likelihood ratio of the diagnostic test for scoliosis progression by the 3-D ultrasound imaging system was 0.08. Conclusion: The 3-D ultrasound imaging method is a valid technique for detecting coronal curve progression as compared with conventional radiography in follow-up of AIS. Substituting conventional radiography with 3-D ultrasound is effective in reducing the radiation dose to which AIS patients are exposed during their follow-up examinations

A population-based cohort study of 394,401 children followed for 10 years exhibits sustained effectiveness of scoliosis screening

© 2015 Elsevier Inc. All rights reserved. Background context: The value of scoliosis screening has been recently shown in a multicenter randomized controlled trial. However, the long-term sustainability of the clinical effectiveness of scoliosis screening as a routine health service remains unknown. Purpose: The aim of this study was to assess the sustainability of the clinical effectiveness of school scoliosis screening. Study design/setting: A large population-based cohort study with a 10-year follow-up was conducted. Patient sample: A total of 394,401 students who were in the fifth grade during the five academic years from 1995/1996 to 1999/2000 formed five consecutive annual cohorts. The students were eligible for the Hong Kong scoliosis screening program, with their screening history and medical records until their nineteenth birthdays being assessed. Outcome measures: The outcome measures considered in the study were development of adolescent idiopathic scoliosis by the 19 years of age and the Cobb angle. Methods: The clinical effectiveness of scoliosis screening was assessed by referral rate for radiographic diagnosis, sensitivity, specificity, and predictive values. Results: A total of 306,144 students (78%) participated in scoliosis screening, which used a two-tier system. The prevalence of curves of 20 or greater was 1.8% (95% confidence interval [CI], 1.7-1.8%), whereas the referral rate for radiography, the sensitivity, and the positive predictive value (PPV) for curves of 20 or greater were 4.1% (95% CI, 4.0-4.2%), 91% (95% CI, 90-92%), and 40% (95% CI, 39-41%), respectively. Across the five consecutive annual cohorts, the prevalence and sensitivity for curves of 20 or greater increased by 0.23% (95% CI, 0.21-0.25%; p<.001) and 0.76% (95% CI, 0.43-1.04%; p<.001) per year, respectively; however, the PPV was reduced by 1.71% (95% CI, 1.09-2.33%; p<.001) per year. Conclusions: This report describes the first large population-based study with a long-term follow-up indicating that a scoliosis screening program can have sustained clinical effectiveness in identifying patients with adolescent idiopathic scoliosis needing clinical observation. As the prevalence of adolescent idiopathic scoliosis increases, scoliosis screening should be continued as a routine health service in schools or by general practitioners if there is no scoliosis screening policy.postprin

Comparison of 3D and 2D characterization of spinal geometry from biplanar X-rays: a large cohort study

Background: Biplanar X-ray system providing anteroposterior and sagittal plane with an ultra-low radiation dose and in weight-bearing position is increasingly used for spine imaging. The original three-dimensional (3D) reconstruction method from biplanar X-rays has been widely used for clinical parameters, however, the main issue is that manual adjustments of the 3D model was quite time-consuming and limited to thoracolumbar spine. A quasi-automated 3D reconstruction method of the spine from cervical vertebra to pelvis was proposed, which proved fast and accurate in 57 patients with adolescent idiopathic scoliosis. The aim of this study was to compare the newly developed technique of quasi-automatic 3D measurement with classical 2D measurements in a large cohort. Methods: A total of 494 adults with biplanar EOS X-ray scanning were included in this study and divided into health and deformity group according to the presence of spinal deformity. The proposed method of quasi-automatic 3D measurement was applied to all these subjects. The radiographic parameters included: thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sagittal vertical axis (SVA), T1 pelvic angle (TPA) in sagittal plane, and cobb angle in coronal plane. Comparison was made between quasi-automatic and manual measurement. Results: The mean age was 53.7±19.9 years old. In the whole population, the mean differences between the two methods were 3.9° for TK (30.5°±9.9° vs. 26.5°±9.3°, P30°, respectively. Correlation analysis showed r2 for all clinical parameters ranged from 0.667 to 0.923. On average, the new method takes 5 minutes to compute all the parameters for one case. Conclusions: In conclusion, this ergonomic and efficient quasi-automatic method for full spine proved fast and accurate measurement in a large population, which showed great potential in extensive clinical applicatio