Rubinstein-Taybi syndrome with scoliosis

<p>Abstract</p> <p>Study Design</p> <p>Case report.</p> <p>Objective</p> <p>The authors present the case of a 14-year-old boy with Rubinstein-Taybi syndrome (RSTS) presenting scoliosis.</p> <p>Summary of Background Data</p> <p>There have been no reports on surgery for RSTS presenting scoliosis.</p> <p>Methods</p> <p>The patient was referred to our hospital for evaluation of a progressive spinal curvature. A standing anteroposterior spine radiograph at presentation to our hospital revealed an 84-degree right thoracic curve from T6 to T12, along with a 63-degree left lumbar compensatory curve from T12 to L4. We planned a two-staged surgery and decided to fuse from T4 to L4. The first operation was front-back surgery because of the rigidity of the right thoracic curve. The second operation of lumbar anterior discectomy and fusion was arranged 9 months after the first surgery to prevent the crankshaft phenomenon due to his natural course of adolescent growth. To avoid respiratory complications, the patient was put on a respirator in the ICU for several days after both surgeries.</p> <p>Results</p> <p>Full-length spine radiographs after the first surgery revealed no instrumentation failure and showed that the right thoracic curve was corrected to 31 degrees and the left lumbar curve was corrected to 34 degrees. No postoperative complications occurred after both surgeries.</p> <p>Conclusions</p> <p>We succeeded in treating the patient without complications. Full-length spine standing radiographs at one year after the second operation demonstrated a stable bony arthrodesis with no loss of initial correction.</p

Mechanical Properties of End-crosslinked Entangled Polymer Networks using Sliplink Brownian Dynamics Simulations

The mechanical properties of a polymeric network containing both crosslinks and sliplinks (entanglements) are studied using a multi-chain Brownian dynamics simulation. We coarse-grain at the level of chain segments connecting consecutive nodes (cross- or sliplinks), with particular attention to the Gaussian statistics of the network. Affine displacement of nodes is not imposed: their displacement as well as sliding of monomers through sliplinks is governed by force balances. The simulation results of stress in uniaxial extension and the full stress tensor in simple shear including the (non-zero) second normal stress difference are presented for monodisperse chains with up to 18 entanglements between two crosslinks. The cases of two different force laws of the subchains (Gaussian chains and chains with finite extensibility) for two different numbers of monomers in a subchain (no = 50 and no = 100) are examined. It is shown that the additivity assumption of slip- and crosslink contribution holds for sufficiently long chains with two or more entanglements, and that it can be used to construct the strain response of a network of infinitely long chains. An important consequence is that the contribution of sliplinks to the small-strain shear modulus is about &#8532; of the contribution of a crosslink

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

The RUDY study platform – a novel approach to patient driven research in rare musculoskeletal diseases

Background: Research into rare diseases is becoming more common, with recognition of the significant diagnostic and therapeutic care gaps. Registries are considered a key research methodology to address rare diseases. This report describes the structure of the Rare UK Diseases Study (RUDY) platform that aims to improve research processes and address many of the challenges of carrying out rare musculoskeletal disease research. RUDY is an internet-based platform with online registration, initial verbal consent, online capture of patient reported outcome measures and events within a dynamic consent framework. The database structure, security and governance framework are described. Results: There have been 380 participants recruited into RUDY with completed questionnaire rates in excess of 50 %. There has been one withdrawal and two participants have amended their consent options. Conclusions: The strengths of RUDY include low burden for the clinical team, low research administration costs with high participant recruitment and ease of data collection and access. This platform has the potential to be used as the model for other rare diseases globally

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

Injection therapy and denervation procedures for chronic low-back pain: a systematic review

Injection therapy and denervation procedures are commonly used in the management of chronic low-back pain (LBP) despite uncertainty regarding their effectiveness and safety. To provide an evaluation of the current evidence associated with the use of these procedures, a systematic review was performed. Existing systematic reviews were screened, and the Cochrane Back Review Group trial register was searched for randomized controlled trials (RCTs) fulfilling the inclusion criteria. Studies were included if they recruited adults with chronic LBP, evaluated the use of injection therapy or denervation procedures and measured at least one clinically relevant outcome (such as pain or functional status). Two review authors independently assessed studies for eligibility and risk of bias (RoB). A meta-analysis was performed with clinically homogeneous studies, and the GRADE approach was used to determine the quality of evidence. In total, 27 RCTs were included, 14 on injection therapy and 13 on denervation procedures. 18 (66%) of the studies were determined to have a low RoB. Because of clinical heterogeneity, only two comparisons could be pooled. Overall, there is only low to very low quality evidence to support the use of injection therapy and denervation procedures over placebo or other treatments for patients with chronic LBP. However, it cannot be ruled out that in carefully selected patients, some injection therapy or denervation procedures may be of benefit

Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit

Haplotype association analyses in resources of mixed structure using Monte Carlo testing

<p>Abstract</p> <p>Background</p> <p>Genomewide association studies have resulted in a great many genomic regions that are likely to harbor disease genes. Thorough interrogation of these specific regions is the logical next step, including regional haplotype studies to identify risk haplotypes upon which the underlying critical variants lie. Pedigrees ascertained for disease can be powerful for genetic analysis due to the cases being enriched for genetic disease. Here we present a Monte Carlo based method to perform haplotype association analysis. Our method, hapMC, allows for the analysis of full-length and sub-haplotypes, including imputation of missing data, in resources of nuclear families, general pedigrees, case-control data or mixtures thereof. Both traditional association statistics and transmission/disequilibrium statistics can be performed. The method includes a phasing algorithm that can be used in large pedigrees and optional use of pseudocontrols.</p> <p>Results</p> <p>Our new phasing algorithm substantially outperformed the standard expectation-maximization algorithm that is ignorant of pedigree structure, and hence is preferable for resources that include pedigree structure. Through simulation we show that our Monte Carlo procedure maintains the correct type 1 error rates for all resource types. Power comparisons suggest that transmission-disequilibrium statistics are superior for performing association in resources of only nuclear families. For mixed structure resources, however, the newly implemented pseudocontrol approach appears to be the best choice. Results also indicated the value of large high-risk pedigrees for association analysis, which, in the simulations considered, were comparable in power to case-control resources of the same sample size.</p> <p>Conclusions</p> <p>We propose hapMC as a valuable new tool to perform haplotype association analyses, particularly for resources of mixed structure. The availability of meta-association and haplotype-mining modules in our suite of Monte Carlo haplotype procedures adds further value to the approach.</p