What aspects of the scoliosis correction are most important to the teenager who has keyhole scoliosis correction surgery? A prospective series of 100 patients

Introduction. Surgical treatment of scoliosis is assessed in the spine clinic by the surgeon making numerous measurements on X-Rays as well as the rib hump. But it is important to understand which of these measures correlate with self-reported improvements in patients’ quality of life following surgery. The objective of this study was to examine the relationship between patient satisfaction after thoracoscopic (keyhole) anterior scoliosis surgery and standard deformity correction measures using the Scoliosis Research Society (SRS) adolescent questionnaire. Methods. A series of 100 consecutive adolescent idiopathic scoliosis patients received a single anterior rod via a keyhole approach at the Mater Children’s Hospital, Brisbane. Patients completed SRS outcomes questionnaires before surgery and again at 24 months after surgery. Multiple regression and t-tests were used to investigate the relationship between SRS scores and deformity correction achieved after surgery. Results. There were 94 females and 6 males with a mean age of 16.1 years. The mean Cobb angle improved from 52º pre-operatively to 21º for the instrumented levels post-operatively (59% correction) and the mean rib hump improved from 16º to 8º (51% correction). The mean total SRS score for the cohort was 99.4/120 which indicated a high level of satisfaction with the results of their scoliosis surgery. None of the deformity related parameters in the multiple regressions were significant. However, the twenty patients with the smallest Cobb angles after surgery reported significantly higher SRS scores than the twenty patients with the largest Cobb angles after surgery, but there was no difference on the basis of rib hump correction. Discussion. Patients undergoing thoracoscopic (keyhole) anterior scoliosis correction report good SRS scores which are comparable to those in previous studies. We suggest that the absence of any statistically significant difference in SRS scores between patients with and without rod or screw complications is because these complications are not associated with any clinically significant loss of correction in our patient group. The Cobb angle after surgery was the only significant predictor of patient satisfaction when comparing subgroups of patients with the largest and smallest Cobb angles after surgery.

Hydrothermal synthesis of single crystallin strontium titanate nanocubes

Strontium titanate nanocubes with an average edge length of 150mm have been successfully synthesized from a simple hydrothermal system. Characterization techniques such as X-ray powder diffraction analysis, scanning electron microscopy and energy-dispersive analysis of X-rays were used to investigate the products. The results showed that as-prepared powders are pure SrTiO3 with cubic shape, which consists with the growth habit of its intrinsic crystal structure. These uniform nanocubes with high crystallinity will exhibit superior physical properties in the practical applications. Furthermore, during the experimental process, it has been found that the dilute acid washing process is very important to obtain high pure SrTiO3.

Antiproton induced DNA damage : proton like in flight, carbon-ion light near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Results using Trabecular Metal™ augments in combination with acetabular impaction bone grafting in deficient acetabula

We examined whether the use of trabecular metal wedges to fill segmental defects is an effective method of socket reconstruction when used in combination with impaction grafting and implantation of a cemented socket. Fifteen hips in 14 patients underwent impaction grafting in combination with a TM wedge with a minimum of 2 years follow-up. All patients had their defects assessed using the Paprosky classification. Patients were reviewed with x-rays and migration of the implant was measured. Outcome scores were also collected. Mean follow-up was 39 months (25-83). The mean age at surgery was 67.8 (49-85) years. Seven of the patients had previously undergone impaction grafting with the use of a stainless steel rim mesh to constrain the graft. None of the patients had failed either clinically or radiologically.

Quantitative estimation of bioturbation based on digital image analysis

Quantitative determination of modification of primary sediment features, by the activity of organisms (i.e., bioturbation) is essential in geosciences. Some methods proposed since the 1960s are mainly based on visual or subjective determinations. The first semiquantitative evaluations of the Bioturbation Index, Ichnofabric Index, or the amount of bioturbation were attempted, in the best cases using a series of flashcards designed in different situations. Recently, more effective methods involve the use of analytical and computational methods such as X-rays, magnetic resonance imaging or computed tomography; these methods are complex and often expensive. This paper presents a compilation of different methods, using Adobe® Photoshop® software CS6, for digital estimation that are a part of the IDIAP (Ichnological Digital Analysis Images Package), which is an inexpensive alternative to recently proposed methods, easy to use, and especially recommended for core samples. The different methods — “Similar Pixel Selection Method (SPSM)”, “Magic Wand Method (MWM)” and the “Color Range Selection Method (CRSM)” — entail advantages and disadvantages depending on the sediment (e.g., composition, color, texture, porosity, etc.) and ichnological features (size of traces, infilling material, burrow wall, etc.). The IDIAP provides an estimation of the amount of trace fossils produced by a particular ichnotaxon, by a whole ichnocoenosis or even for a complete ichnofabric. We recommend the application of the complete IDIAP to a given case study, followed by selection of the most appropriate method. The IDIAP was applied to core material recovered from the IODP Expedition 339, enabling us, for the first time, to arrive at a quantitative estimation of the discrete trace fossil assemblage in core samples.

Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas

Background: The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)-12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side-effects of IL-12 gene therapy, the objective was to achieve the controlled release of IL-12 after intramuscular gene electrotransfer. Methods: Gene electrotransfer of the plasmid pORF-mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL-12 was monitored in the serum of mice after carrying out two sets of intramuscular IL-12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL-12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X-rays, was evaluated on subcutaneous SA-1 and LPB tumors, as well as on lung metastases. Results: A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL-12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3-fold was determined. The amount of circulating IL-12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid. Conclusions: The present study demonstrates the feasibility of treatment by IL-12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.

Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.

Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden

Evaluation of protein and metabolite expression patterns in blood using mass spectrometry and high-throughput antibody-based screening platforms has potential for the discovery of new biomarkers for managing breast cancer patient treatment. Previously identified blood-based breast cancer biomarkers, including cancer antigen 15.3 (CA15-3) are useful in combination with imaging (computed tomography scans, magnetic resonance imaging, X-rays) and physical examination for monitoring tumour burden in advanced breast cancer patients. However, these biomarkers suffer from insufficient levels of accuracy and with new therapies available for the treatment of breast cancer, there is an urgent need for reliable, non-invasive biomarkers that measure tumour burden with high sensitivity and specificity so as to provide early warning of the need to switch to an alternative treatment. The aim of this study was to identify a biomarker signature of tumour burden using cancer and non-cancer (healthy controls/non-malignant breast disease) patient samples. Results demonstrate that combinations of three candidate biomarkers from Glutamate, 12-Hydroxyeicosatetraenoic acid, Beta-hydroxybutyrate, Factor V and Matrix metalloproteinase-1 with CA15-3, an established biomarker for breast cancer, were found to mirror tumour burden, with AUC values ranging from 0.71 to 0.98 when comparing non-malignant breast disease to the different stages of breast cancer. Further validation of these biomarker panels could potentially facilitate the management of breast cancer patients, especially to assess changes in tumour burden in combination with imaging and physical examination.

An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12

Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

The effect of hip muscle strengthening on pain and disability for individuals with non-specific low back pain : a randomized controlled trial

Introduction Clinical guidelines for the treatment of chronic low back pain suggest the use of supervised exercise. Motor control (MC) based exercise is widely used within clinical practice but its efficacy is equivalent to general exercise therapy. MC exercise targets the trunk musculature. Considering the mechanical links between the hip, pelvis, and lumbar spine, surprisingly little focus has been on investigating the contribution of the hip musculature to lumbopelvic support. The purpose of this study is to compare the efficacy of two exercise programs for the treatment of non-specific low back pain (NSLBP). Methods Eighty individuals aged 18-65 years of age were randomized into two groups to participate in this trial. The primary outcome measures included self-reported pain intensity (0-100mm VAS) and percent disability (Oswestry Disability Index V2). Bilateral measures of hip strength (N/kg) and two dimensional frontal plane mechanics (º) were the secondary outcomes. Outcomes were measured at baseline and following a six-week home based exercise program including weekly sessions of real-time ultrasound imaging. Results Within group comparisons revealed clinically meaningful reductions in pain for both groups. The MC exercise only (N= 40, xˉ =-20.9mm, 95%CI -25.7, -16.1) and the combined MC and hip exercise (N= 40, xˉ = -24.9mm, 95%CI -30.8, -19.0). There was no statistical difference in the change of pain (xˉ =-4.0mm, t= -1.07, p=0.29, 95%CI -11.5, 3.5) or disability (xˉ =-0.3%, t=-0.19, p=0.85, 95%CI -11.5, 3.5) between groups. Conclusion Both exercise programs had similar and positive effects on NSLBP which support the use of the home based exercise programs with weekly supervised visits. However, the addition of specific hip strengthening exercises to a MC based exercise program did not result in significantly greater reductions in pain or disability. Trial Registration NCTO1567566 Funding: Worker’s Compensation Board Alberta Research Grant.

'Sink or swim': An evaluation of the clinical characteristics of individuals with high bone mass

Summary High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. Introduction High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Methods Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Results Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m 2, p < 0.001). Conclusion Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Migraine is a debilitating neurological disorder affecting around 1 in 7 people worldwide, but its molecular mechanisms remain poorly understood. Some debate exists over whether migraine is a disease of vascular dysfunction, or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we performed the largest genetic study of migraine to date, comprising 59,674 cases and 316,078 controls from 22 GWA studies. We identified 45 independent single nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 x 10-8) that map to 38 distinct genomic loci, including 28 loci not previously reported and the first locus identified on chromosome X. Furthermore, a subset analysis for migraine without aura (MO) identified seven of the same loci as from the full sample, whereas no loci reached genome-wide significance in the migraine with aura (MA) subset. In subsequent computational analyzes, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men

Context: High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear. Objective: To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover. Design, Setting, and Participants: We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. Atotal of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls. Main Outcome Measures: We measured fat mass, by DXA, and bone turnover markers. Results: Amongwomen, fat mass was inversely related to age in controls (P<.01), but not in HBM cases (P<.96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P<.001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P<.002); however, lean mass increases wereless marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P<.001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5]μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P<.001). Conclusions: HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover. Copyright © 2013 by The Endocrine Society.

Elevated circulating sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations

CONTEXT: The role and importance of circulating sclerostin is poorly understood. High bone mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. OBJECTIVE: Our objective was to determine circulating sclerostin concentrations in HBM. DESIGN AND PARTICIPANTS: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. MAIN MEASURES: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. RESULTS: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P < .01). CONCLUSIONS: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.