Citations

ABSTRACTFibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT‐PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor β (TGF‐β), and SMAD3 (P < 0.05) which significantly corroborate the fold changes found in the fibrosis arrays. To further explore the nature of SSCT fibrosis, cells were isolated from patient and control tissue. Col1, Col3, TGF‐β, and SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (P < 0.05). Further, fibrotic genes expression was decreased by inhibiting TGF‐β receptor I (TβRI) activity (P < 0.05). TGF‐β second messenger SMAD activity was significantly activated in SSCT fibroblasts from patients and this activation was abrogated by inhibiting TβRI signaling (P < 0.05). These findings suggest that blocking TGF‐β signaling may be an important therapeutic approach to treating the underlying fibrosis of SSCT in CTS patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1444–1450, 2014.

BackgroundWe aimed to determine the long‐term outcomes of percutaneous lead extraction and stent placement in patients with pacemaker‐induced superior vena cava (SVC) syndrome.MethodsThe study retrospectively screened patients who underwent lead extraction followed by central vein stent implantation at Mayo Clinic (Rochester, MN, USA), from January 2005 to December 2012, to identify the patients with pacemaker‐induced SVC syndrome. Demographic, clinical, and follow‐up characteristics of those patients were collected from electronic medical records.ResultsSix cases were identified. The mean (standard deviation) age was 56 (15) years (male, 67%). All patients had permanent dual‐chamber pacemakers, with a mean 11‐year history of pacemaker placement. The entire device system was explanted in five patients; one patient had a 21‐year‐old pacemaker lead that could not be removed. Eight stents were implanted in six patients: five patients had one stent, one patient had three. A new pacemaker system was reimplanted through the stented vein in five patients. Technical success was achieved in all patients, without any complication. Symptoms rapidly resolved in all patients after stent deployment. The mean follow‐up duration was 48 months (range, 10–100 months). Three patients remained symptom free. Reintervention with percutaneous balloon venoplasty was successful in three patients with symptom recurrence.ConclusionPercutaneous stent implantation after lead removal followed by reimplantation of leads is a feasible alternative therapy for pacemaker‐induced SVC syndrome, although some cases may require repeat intervention.

Key Points Methylation analysis at ZAP-70 CpG+223 in CLL provides superior prognostic information vs IGHV status or CD38 or ZAP-70 expression. A pyrosequencing method for the feasible assessment of CpG+223 methylation in CLL samples is provided.

Elasticity imaging has emerged as a viable clinical tool for assisting in diagnosis of certain diseases such as liver fibrosis and cancer. Many methods have been developed for generating and measuring shear waves in soft tissues. The advantage of using shear waves is that the shear wave velocity is proportional to the mechanical material properties of the tissues under investigation. Soft tissues are inherently viscoelastic and considerable effort has been made to quantify the dispersion, or variation of frequency, of the velocity and attenuation of shear waves. This is accomplished by measuring the shear wave motion and using Fourier-based techniques to extract the shear wave velocity and attenuation. Additional considerations are made in tissues where geometric dispersion is also present such as in the heart. Viscoelastic characterization of the shear viscoelasticity of soft tissues in vivo such as human liver, human kidney, and swine heart will be shown. We will also demonstrate parameterization of the results by using a model-free approach or by fitting the shear wave velocity dispersion to rheological models. The diagnostic value of the viscoelastic parameters will be discussed for each particular application. [This work was supported in part by NIH Grant Nos. DK092255, DK082408, and EB002167.]

AbstractNoninflammatory subsynovial connective tissue (SSCT) fibrosis with nerve compression is a prominent feature of carpal tunnel syndrome (CTS). Studies have shown that SSCT matrix synthesis and material property changes in CTS are associated with increased activity of transforming growth factor (TGF)‐β1. The aim of this study were to (1) investigate the ability of SSCT fibroblasts from CTS patients and unaffected individuals to contract a collagen gel ring and (2) determine how the addition of TGF‐β1 affects this ability. SSCT fibroblasts from three normal cadavers and three age‐matched female patients who had undergone surgery for CTS were used. Results showed patient cell‐seeded gels had a significantly higher contraction rate (p < 0.001) than control cells, and fully contracted gel rings possessed a significantly higher tensile strength (p = 0.003) and stiffness (p < 0.001). Furthermore, TGF‐β1 significantly intensified contraction rate (p < 0.001), tensile strength (p < 0.001), and stiffness (p < 0.001). In conclusion, SSCT cells from normal donors and CTS patients contract collagen gel rings differently, and this ability is affected by TGF‐β1 treatment. This cell‐seeded collagen gel model may be useful for developing new methods of stopping or eliminating the effect of TGF‐β1 on the SSCT fibroblasts and surrounding matrix, which might aid in the identification of medical treatment for CTS. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 574–580, 2015.

AbstractAlthough coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult‐onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw‐opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult‐onset primary dystonia.

Background This study investigated the effects of a series of four hypertonic dextrose injections on the subsynovial connective tissue (SSCT) and median nerve within the carpal tunnel of a rabbit model. Methods Twenty New Zealand white rabbits were used. One forepaw carpal tunnel was randomly injected with 0.1 ml of 10 % dextrose solution. The contralateral forepaw was injected with a similar amount of saline. This injection was made once per week for 4 weeks. The animals were killed at 16 weeks after the initial injection and were evaluated by electrophysiology (EP), SSCT mechanical testing, and histology. Results Mechanical testing revealed significantly greater ultimate load and energy absorption in the dextrose injection group compared to the saline injection group ( P<0.05). Histological evaluation revealed SSCT fibrosis and thickening and edema in the median nerve bundles in the dextrose injection group. There was a prolongation in the latency of the EP test in the dextrose injection group ( P=0.08). Conclusions Previous studies had shown that one or two injections of 10 % dextrose could induce moderate SSCT fibrosis and mild EP changes without nerve histology changes. In this study, we have shown that higher doses create more severe fibrosis and, most importantly, more severe neuropathy, suggesting a dose–response effect, and confirming this as a potentially useful animal model for researching the etiology and treatment of carpal tunnel syndrome.

Purpose The purpose of this in vitro biomechanical study was to assess the effects of the remplissage procedure for small‐ and large‐sized Hill‐Sachs lesions (HSLs) on shoulder range of motion (ROM) with a special interest in the apprehension position. Methods HSLs of 50% and 100% of the glenoid width were simulated in 7 cadaveric shoulders as small and large lesions, respectively, and the postoperative condition was reproduced by placing suture anchors on the articular surface and tying down the infraspinatus at the medial edge of the would‐be lesion site. ROMs were measured in abduction, internal rotation, and external rotation with the humerus in the adducted and abducted position. In addition, the ROM was measured in the anterior apprehension position, in which 2 torques of external rotation and extension were applied simultaneously, and external rotation and horizontal extension ROMs were measured with the humerus in different abduction angles (20°, 40°, and 60°). Results For standard ROMs, the procedure for the 50% HSL maintained complete ROMs, whereas the procedure for the 100% HSL significantly decreased external rotation ROM with the humerus in both the adducted and abducted positions, as well as abduction ROM. In the apprehension position, remplissage for the 50% HSL decreased extension ROM with the humerus abducted to 40° and 60°. Remplissage for the 100% HSL significantly decreased both external and extension ROMs regardless of the humeral abduction angle. Conclusions In the cadaveric model with an intact humeral head and the simulated postoperative condition, the remplissage procedure for a large HSL caused significant restrictions in ROM of abduction in the scapular plane and external rotation with the humerus in both adduction and abduction. It also caused significant restrictions in both external rotation and extension ROMs in the apprehension position. Clinical Relevance The indication for the remplissage procedure for the larger HSL should be considered carefully, especially for the competitive throwing athlete who needs exceptional external rotation ROM for optimal overhead throwing performance.

Abstract Motivation: Reference genome assemblies are subject to change and refinement from time to time. Generally, researchers need to convert the results that have been analyzed according to old assemblies to newer versions, or vice versa, to facilitate meta-analysis, direct comparison, data integration and visualization. Several useful conversion tools can convert genome interval files in browser extensible data or general feature format, but none have the functionality to convert files in sequence alignment map or BigWig format. This is a significant gap in computational genomics tools, as these formats are the ones most widely used for representing high-throughput sequencing data, such as RNA-seq, chromatin immunoprecipitation sequencing, DNA-seq, etc. Results: Here we developed CrossMap, a versatile and efficient tool for converting genome coordinates between assemblies. CrossMap supports most of the commonly used file formats, including BAM, sequence alignment map, Wiggle, BigWig, browser extensible data, general feature format, gene transfer format and variant call format. Availability and implementation: CrossMap is written in Python and C. Source code and a comprehensive user’s manual are freely available at: http://crossmap.sourceforge.net/. Contact: Kocher.JeanPierre@mayo.edu or wang.liguo@mayo.edu Supplementary information: Supplementary data are available at Bioinformatics online.

The supraspinatus tendon consists morphologically of two sub‐regions, anterior and posterior. The anterior sub‐region is thick and tubular while the posterior is thin and strap‐like. The purpose of this study was to compare the structural and mechanical properties of the anterior and posterior sub‐regions of the supraspinatus tendon. The supraspinatus tendons from seven human cadaveric shoulders were morphologically divided into the anterior and posterior sub‐regions. Length, width, and thickness were measured. A servo‐hydraulic testing machine (MTS Systems Corporation, Minneapolis, MN) was used for tensile testing. The maximal load at failure, modulus of elasticity and ultimate tendon stress were calculated. Repeated measures were used for statistical comparisons. The mean anterior tendon cross‐sectional area was 47.3 mm2 and the posterior was 32.1 mm2. Failure occurred most often at the insertion site: anterior (5/7) and posterior (6/7). All parameters of the anterior sub‐region were significantly greater than those of the posterior sub‐region. The moduli of elasticity at the insertion site were 592.4 MPa in the anterior sub‐region and 217.7 MPa in the posterior (P = 0.01). The ultimate failure loads were 779.2 N in the anterior sub‐region and 335.6 N in the posterior (P = 0.003). The ultimate stresses were 22.1 MPa in the anterior sub‐region and 11.6 MPa in the posterior (P = 0.008). We recognized that the anterior and posterior sub‐regions of the SSP tendon have significantly different mechanical properties. In a future study, we need to evaluate how best to repair an SSP tendon considering these region‐specific properties. Clin. Anat. 27:702–706, 2014. © 2013 Wiley Periodicals, Inc.