Novel SCN5A mutation associated with idiopathic ventricular fibrillation due to subclinical Brugada syndrome

Idiopathic ventricular fibrillation can be caused by subclinical channelopathies such as Brugada syndrome. Our objective is to study the clinical behaviour of a new SCN5A mutation found in a woman with idiopathic ventricular fibrillation. A 53-year-old woman presented with multiple episodes of ventricular fibrillation, a structurally normal heart and normal baseline electrocardiogram. Genetic testing included KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 and identified a mutation in SCN5A (D1816fs/g98747-98748insT). We studied 15 immediate family members by means of electrocardiogram, echocardiogram, flecainide challenge test and genetic study. Eight subjects had the mutation. The flecainide challenge test was positive for Brugada syndrome in two subjects in the case group and none in the control group. The PR and QRS intervals on the baseline electrocardiogram were longer in the case group. The left atrial volume indexed to body surface was higher in the case group, likely due to the fact that two patients with the mutation had atrial fibrillation and none had it in the control group. The D1816fs/g98747-98748insT mutation in SCN5A may be associated with idiopathic ventricular fibrillation and Brugada syndrome with a broad phenotypic spectrum and incomplete penetrance. Genetic testing may be useful to identify the etiology of idiopathic ventricular fibrillation in patients with a negative thorough clinical evaluation

Free Form Deformation-Based Image Registration Improves Accuracy of Traction Force Microscopy

Traction Force Microscopy (TFM) is a widespread method used to recover cellular tractions from the deformation that they cause in their surrounding substrate. Particle Image Velocimetry (PIV) is commonly used to quantify the substrate's deformations, due to its simplicity and efficiency. However, PIV relies on a block-matching scheme that easily underestimates the deformations. This is especially relevant in the case of large, locally non-uniform deformations as those usually found in the vicinity of a cell's adhesions to the substrate. To overcome these limitations, we formulate the calculation of the deformation of the substrate in TFM as a non-rigid image registration process that warps the image of the unstressed material to match the image of the stressed one. In particular, we propose to use a B-spline -based Free Form Deformation (FFD) algorithm that uses a connected deformable mesh to model a wide range of flexible deformations caused by cellular tractions. Our FFD approach is validated in 3D fields using synthetic (simulated) data as well as with experimental data obtained using isolated endothelial cells lying on a deformable, polyacrylamide substrate. Our results show that FFD outperforms PIV providing a deformation field that allows a better recovery of the magnitude and orientation of tractions. Together, these results demonstrate the added value of the FFD algorithm for improving the accuracy of traction recovery.Funded by Ministerio de Economía y Competividad (ES); url: http://www.mineco.gob.es/; RyC2010-06094, Fundación Ramón Areces (ES); url: http://www.fundacionareces.es/fundacionareces/, Ministerío de Economía y Competividad (ES); url: http://www.mineco.gob.es/; SAF2011-24953 (MVM); Ministerio de Economía y Competividad (ES); url: http://www.mineco.gob.es/; DPI2012-38090-C1, European Research Council (BE); url: http://erc.europa.eu/; 306751 (JMGA); European Research Council (BE); url: http://erc.europa.eu/; 308223 (HVO); Ministerio de Economía y Competividad (ES); url: http://www.mineco.gob.es/; DPI2012-38090-C3 (COS); and Ministerio de Economía y Competividad (ES); url: http://www.mineco.gob.es/; TEC2013- 48552-C2-1-R (AMB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.European Community's Seventh Framework Progra

Full L-1-regularized Traction Force Microscopy over whole cells

Traction Force Microscopy (TFM) is a widespread technique to estimate the tractions that cells exert on the surrounding substrate. To recover the tractions, it is necessary to solve an inverse problem, which is ill-posed and needs regularization to make the solution stable. The typical regularization scheme is given by the minimization of a cost functional, which is divided in two terms: the error present in the data or data fidelity term; and the regularization or penalty term. The classical approach is to use zero-order Tikhonov or L2-regularization, which uses the L2-norm for both terms in the cost function. Recently, some studies have demonstrated an improved performance using L1-regularization (L1-norm in the penalty term) related to an increase in the spatial resolution and sensitivity of the recovered traction field. In this manuscript, we present a comparison between the previous two regularization schemes (relying in the L2-norm for the data fidelity term) and the full L1-regularization (using the L1-norm for both terms in the cost function) for synthetic and real data. Our results reveal that L1-regularizations give an improved spatial resolution (more important for full L1-regularization) and a reduction in the background noise with respect to the classical zero-order Tikhonov regularization. In addition, we present an approximation, which makes feasible the recovery of cellular tractions over whole cells on typical full-size microscope images when working in the spatial domain. The proposed full L1-regularization improves the sensitivity to recover small stress footprints. Moreover, the proposed method has been validated to work on full-field microscopy images of real cells, what certainly demonstrates it is a promising tool for biological applications.status: publishe

Comparison of the short-term outcomes between trigger point dry needling and trigger point manual therapy for the management of chronic mechanical neck pain: A randomized clinical trial

• STUDY DESIGN: Randomized clinical study. • OBJECTIVES: To compare the effects of trigger point (TrP) dry needling (DN) and TrP manual therapy (MT) on pain, function, pressure pain sensitivity, and cervical range of motion in subjects with chronic mechanical neck pain. • BACKGROUND: Recent evidence suggests that TrP DN could be effective in the treatment of neck pain. However, no studies have directly compared the outcomes of TrP DN and TrP MT in this population. • METHODS: Ninety-four patients (mean ± SD age, 31 ± 3 years; 66% female) were randomized into a TrP DN group (n = 47) or a TrP MT group (n = 47). Neck pain intensity (11-point numeric pain rating scale), cervical range of motion, and pressure pain thresholds (PPTs) over the spinous process of C7 were measured at baseline, postintervention, and at follow-ups of 1 week and 2 weeks after treatment. The Spanish version of the Northwick Park Neck Pain Questionnaire was used to measure disability/function at baseline and the 2-week follow-up. Mixed-model, repeated-measures analyses of variance (ANOVAs) were used to determine if a time-by-group interaction existed on the effects of the treatment on each outcome variable, with time as the within-subject variable and group as the between-subject variable. • RESULTS: The ANOVA revealed that participants who received TrP DN had outcomes similar to those who received TrP MT in terms of pain, function, and cervical range of motion. The 4-by-2 mixed-model ANOVA also revealed a significant time-by-group interaction (P\u3c.001) for PPT: patients who received TrP DN experienced a greater increase in PPT (decreased pressure sensitivity) than those who received TrP MT at all follow-up periods (between-group differences: posttreatment, 59.0 kPa; 95% confidence interval [CI]: 40.0, 69.2; 1-week follow-up, 69.2 kPa; 95% CI: 49.5, 79.1; 2-week follow-up, 78.9 kPa; 95% CI: 49.5, 89.0). • CONCLUSION: The results of this clinical trial suggest that 2 sessions of TrP DN and TrP MT resulted in similar outcomes in terms of pain, disability, and cervical range of motion. Those in the TrP DN group experienced greater improvements in PPT over the cervical spine. Future trials are needed to examine the effects of TrP DN and TrP MT over long-term follow-up periods

Free Form Deformation -based Image Registration Improves Accuracy of Traction Force Microscopy

Traction Force Microscopy (TFM) is a widespread method used to recover cellular tractions from the deformation that they cause in their surrounding substrate. Particle Image Velocimetry (PIV) is commonly used to quantify the substrate’s deformations, due to its simplicity and efficiency. However, PIV relies on a block-matching scheme that easily underestimates the deformations. This is especially relevant in the case of large, locally non-uniform deformations as those usually found in the vicinity of a cell’s adhesions to the substrate. To overcome these limitations, we formulate the calculation of the deformation of the substrate in TFM as a non-rigid image registration process that warps the image of the unstressed material to match the image of the stressed one. In particular, we propose to use a B-spline -based Free Form Deformation (FFD) algorithm that uses a connected deformable mesh to model a wide range of flexible deformations caused by cellular tractions. Our FFD approach is validated in 3D fields using synthetic (simulated) data as well as with experimental data obtained using isolated endothelial cells lying on a deformable, polyacrylamide substrate. Our results show that FFD outperforms PIV providing a deformation field that allows a better recovery of the magnitude and orientation of tractions. Together, these results demonstrate the added value of the FFD algorithm for improving the accuracy of traction recovery.status: publishe

Displacements obtained from a circular traction patch of 6μm diameter exerting a load of 10% of the Young modulus along the X-axis.

<p>(a) Magnitude of the displacement field provided by the simulated ground-truth data, (b) PIV algorithm and (c) FFD algorithm. Cones indicate the direction of the field at those locations where the magnitude is larger than 20% of the peak magnitude. Units are given in μm. The scale bars represent 5μm.</p

Displacements of fluorescent beads induced by a GFP-HUVEC on a 1.3 kPa PAA gel.

<p>(a) Maximum intensity projection of the fluorescent image of the HUVEC. (b) Pseudo-color image showing the fluorescent beads at the gel surface. The beads in the unstressed and stressed gel are pseudo-colored in red and green, respectively. The contrast of the pseudo-color image has been modified to highlight the areas with bead displacements. The scale bar represents 30μm.</p

Quantitative performance evaluation of the recovered total force magnitude and average orientation within the segmented stress footprint for FFD and PIV algorithms within a TFM framework.

<p>Quantitative performance evaluation of the recovered total force magnitude and average orientation within the segmented stress footprint for FFD and PIV algorithms within a TFM framework.</p

Tractions obtained from a circular traction patch of 6μm diameter exerting a load of 10% of the Young’s modulus along the X-axis.

<p>From left to right, simulated tractions, results from PIV, and results from FFD. (a) Magnitude of the traction field before and after segmenting the stress footprint and, (b) its corresponding orientation with the elevation angle indicated by the colormap. Units of the magnitude are given as percentage of the Young’s modulus. Units of the elevation angles (with respect to X-axis) are given in degrees. The scale bar represents 5μm.</p