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Plasticity is a fundamental property of neurons in both the central and peripheral nervous systems, enabling rapid changes in neural network function. The intracardiac nervous system (ICNS) is an extensive network of neurons clustered into ganglionated plexi (GP) on the surface of the heart. GP neurons are the final site of neuronal control of heart rhythm, and pathophysiological remodeling of the ICNS is proposed to feature in multiple cardiovascular diseases, including heart failure and atrial fibrillation. To examine the potential role of GP neuron plasticity in atrial arrhythmia and hypertension, we developed whole cell patch clamp recording techniques from GP neurons in isolated ICNS preparations from aged control (Wistar-Kyoto) and spontaneously hypertensive rats (SHRs). Anesthetized SHRs showed frequent premature ventricular contractions and episodes of atrial arrhythmia following carbachol injection, and isolated SHR atrial preparations were susceptible to pacing induced atrial arrhythmia. Whole cell recordings revealed elevated spontaneous postsynaptic current frequency in SHR GP neurons, as well as remodeled electrophysiology, with significant decreases in action potential amplitude and half-width. SHRs also showed a parallel increase in the number of cholinergic neurons and adrenergic glomus cells in cardiac ganglia, a higher proportion of synaptic α7-subunit but not β2-containing nicotinic receptors, and an elevation in the number of synaptic terminals onto GP neurons. Our data show that significant structural and functional plasticity occurs in the intracardiac nervous system and suggest that enhanced excitability through synaptic plasticity, together with remodeling of cardiac neuron electrophysiology, contributes to the substrate for atrial arrhythmia in hypertensive heart disease.NEW & NOTEWORTHY We have developed intracardiac neuron whole cell recording techniques in atrial preparations from control and spontaneous hypertensive rats. This has enabled the identification of significant synaptic plasticity in the intracardiac nervous system, including enhanced postsynaptic current frequency, increased synaptic terminal density, and altered postsynaptic receptors. This increased synaptic drive together with altered cardiac neuron electrophysiology could increase intracardiac nervous system excitability and contribute to the substrate for atrial arrhythmia in hypertensive heart disease.

Heart failure (HF) is one of the leading causes of death worldwide. HF is associated with substantial microstructural remodeling, which is linked to changes in left ventricular geometry and impaired cardiac function. The role of myocardial remodeling in altering the mechanics of failing hearts remains unclear. Structurally based constitutive modeling provides an approach to improve understanding of the relationship between biomechanical function and tissue organization in cardiac muscle during HF. In this study, we used cardiac magnetic resonance imaging and extended-volume confocal microscopy to quantify the remodeling of left ventricular geometry and myocardial microstructure of healthy and spontaneously hypertensive rat hearts at the ages of 12 and 24 months. Passive cardiac mechanical function was characterized using left ventricular pressure-volume compliance measurements. We have developed a, to our knowledge, new structurally based biomechanical constitutive equation built on parameters quantified directly from collagen distributions observed in confocal images of the myocardium. Three-dimensional left ventricular finite element models were constructed from subject-specific in vivo magnetic resonance imaging data. The structurally based constitutive equation was integrated into geometrically subject-specific finite element models of the hearts and used to investigate the underlying mechanisms of ventricular dysfunction during HF. Using a single pair of material parameters for all hearts, we were able to produce compliance curves that reproduced all of the experimental compliance measurements. The value of this study is not limited to reproducing the mechanical behavior of healthy and diseased hearts, but it also provides important insights into the structure-function relationship of diseased myocardium that will help pave the way toward more effective treatments for HF.

Building anatomically accurate models of the coronary vascular system enables potentially deeper understandings of coronary circulation. To achieve this, (a) images at different levels of vascular network-arteries, arterioles, capillaries, venules, and veins-need to be obtained through suitable imaging modalities; and (b) from images, morphological and topological information needs to be extracted using image processing techniques. While there are several modalities that enable the imaging of large vessels, microcirculation imaging-capturing vessels having diameter lesser than 100 μm-has to date been typically confined to small regions of the heart. This spatially limited microcirculatory information has often been used within cardiac models, with the potentially erroneous assumption that it is representative of the whole organ. However, with the recent advancements in imaging and image processing, it is rapidly becoming feasible to acquire, process, and quantify microcirculation data at the scale of whole organ. In this review, we summarize the progress toward this goal followed through a presentation of the current state-of-the-art imaging and image processing techniques in the context of coronary microcirculation extraction, prominently but not exclusively, from small animals.

Background: Inverse electrocardiographic mapping reconstructs cardiac electrical activity from recorded body surface potentials. This noninvasive technique has been used to identify potential ablation targets. Despite this, there has been little systematic evaluation of its reliability. Methods: Torso and ventricular epicardial potentials were recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, epicardial, and endocardial ventricular pacing (70 records in total). Body surface and cardiac electrode positions were determined and registered using magnetic resonance imaging. Epicardial potentials were reconstructed during ventricular activation using experiment-specific magnetic resonance imaging–based thorax models, with homogeneous or inhomogeneous (lungs, skeletal muscle, fat) electrical properties. Coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions were compared. Inverse mapping underestimated epicardial potentials >2-fold ( P RESULTS: Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60±0.08 to 0.64±0.07 across all methods. Epicardial electrograms were recovered with reasonable fidelity at ≈50% of sites (median correlation coefficient, 0.69–0.72), but variation was substantial. General activation spread was reproduced (median correlation coefficient, 0.72–0.78 for activation time maps after spatio-temporal smoothing). Epicardial foci were identified with a median location error ≈16 mm (interquartile range, 9–29 mm). Inverse mapping with meshless method of fundamental solutions was better than with finite/boundary element methods, and the latter were not improved by inclusion of inhomogeneous torso electrical properties. Conclusions: Inverse potential mapping provides useful information on the origin and spread of epicardial activation. However the spatio-temporal variability of recovered electrograms limit resolution and must constrain the accuracy with which arrhythmia circuits can be identified independently using this approach.

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modelling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the ‘longitudinal’ direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

Recognition of facial beauty is both inborn and learned through social discourses and exposures. Demographic shifts across the globe, in addition to cross-cultural interactions that typify 21st century globalization in virtually all industries, comprise major active evolutionary forces that reshape our individual notions of facial beauty. This article highlights the changing perceptions of beauty, while defining and distinguishing natural beauty and artificial beauty.

The mechanical properties of myocardial tissue are primarily determined by the organisation of the collagen network. Quantitative measurements of collagen morphology can help to understand the structure-function relationship in cardiac tissue. In this study, we segmented collagen from high-resolution three-dimensional (3D) images of the left ventricle (LV) mid-wall myocardium obtained using extended-volume confocal microscopy. 3D shape analysis was used to compute the morphological parameters elongation (e), flatness (f), and anisotropy (a). We applied this analysis to both control and hypertensive rat hearts and showed distinct differences between the control and remodelled hearts, particularly in collagen elongation. The predominant form of collagen in the control rat is elongated with a value of e = 0.846 ± 0.041, whereas in the hypertensive rat collagen, is arranged mostly in a sheet-like form with e = 0.301 ± 0.023. Such quantitative information can be used to develop microstructural models of the myocardium that link the observed changes in cardiac microstructure to changes in mechanical function during the progression of heart diseases, which will help to elucidate the underlying pathological mechanisms.

Understanding of the microvasculature has previously been limited by the lack of methods capable of capturing and modelling complete vascular networks. We used novel imaging and computational techniques to establish the topology of the entire blood vessel network of a murine lymph node, combining 63706 confocal images at 2 μm pixel resolution to cover a volume of 3.88 mm3. Detailed measurements including the distribution of vessel diameters, branch counts, and identification of voids were subsequently re-visualised in 3D revealing regional specialisation within the network. By focussing on critical immune microenvironments we quantified differences in their vascular topology. We further developed a morphology-based approach to identify High Endothelial Venules, key sites for lymphocyte extravasation. These data represent a comprehensive and continuous blood vessel network of an entire organ and provide benchmark measurements that will inform modelling of blood vessel networks as well as enable comparison of vascular topology in different organs.

Background— Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation. Methods and Results— Atrial surface geometry and myofiber orientations were reconstructed in 3D at 50×50×50-μm 3 resolution from serial images acquired throughout the sheep atrial chambers. Myofiber orientations were determined by Eigen-analysis of the structure tensor. These data have been incorporated into an anatomic model that provides the first quantitative representation of myofiber architecture throughout the atrial chambers. By simulating activation on this 3D structure, we have confirmed the roles of specialized myofiber tracts such as the crista terminalis, pectinate muscles, and the Bachman bundle on the spread of activation from the sinus node. We also demonstrate how the complex myocyte arrangement in the posterior left atrium contributes to activation time dispersion adjacent to the pulmonary veins and increased vulnerability to rhythm disturbance generated by ectopic stimuli originating in the pulmonary vein sleeves. Conclusions— We have developed a structurally detailed, image-based model of atrial anatomy that provides deeper understanding of the role that myocyte architecture plays in normal and abnormal atrial electric function.

Transient post-thyroidectomy hypocalcemia is a common complication following thyroid surgery. Studies have identified risk factors and possible ways to help predict post-thyroidectomy hypocalcemia with the intent of ultimately limiting its incidence. This study evaluates the role of patient gender as a potential risk factor.A retrospective case series with chart review of 270 consecutive total thyroidectomy patients was conducted.Jewish General Hospital, a McGill University-affiliated hospital in Montreal, Canada.219 women and 51 men were included. Postoperative hypocalcemia was defined as any 1 of the following: total serum calcium 1.90 mmol/L or less, or signs and symptoms of hypocalcemia. The following were evaluated as potential confounding factors in the study: age, menopause, preoperative calcium, parathyroid hormone, magnesium and phosphate levels, presence of carcinoma in the surgical specimen, number of parathyroid glands preserved in situ, thyroid gland volume, and nodule size.Female patients experienced transient postoperative hypocalcemia in 24.7% (54/219) of cases, which was significantly greater than the 11.8% (6/51) incidence detected in men (P.05). This represents a female/male relative risk ratio of 2.1 (confidence interval, 1.0-4.6). There was no significant difference in rates of hypocalcemia between premenopausal and postmenopausal women (22.7% vs 26.6%).These findings suggest that being female is likely a risk factor for transient post-thyroidectomy hypocalcemia. Although this association is statistically significant, its magnitude and clinical relevance are uncertain and may be trivial. Additional research is needed to ascertain the physiologic mechanisms underlying this gender difference.

We report the first case of hepatoid adenocarcinoma of the skull base, as well as the first reported case in the head and neck region. Hepatoid adenocarcinoma is a rare, aggressive, extrahepatic malignancy with a distinct morphological similarity to hepatocellular carcinoma, in the absence of primary hepatic disease. A 45-year-old man presented with sinus headaches and retro-orbital pain and was found to have a nasopharyngeal mass on endoscopy and a large, destructive sinonasal mass extending intracranially on imaging. Histo- and cytopathological features were similar to hepatocellular carcinoma, and the cells were immunoreactive for α-fetoprotein, epithelial membrane antigen, periodic acid-Schiff, cytokeratin (CK)8/18, CK19, and S100.

Objectives. The goal of the present study is to determine whether a decline in the 1-hour postoperative parathyroid hormone (PTH) level relative to the preoperative level is predictive of hypocalcemia. Methods. This is a retrospective study involving 142 consecutive patients who underwent total thyroidectomy. Changes in preoperative PTH levels were then compared with the 1-hour levels. Results. Thirty-four of 142 patients (23.9%) who underwent total thyroidectomy developed hypocalcemia. Thirty-one of the 34 patients who became hypocalcemic had a 1-hour postoperative PTH drop of 70% or more when compared with the preoperative value (sensitivity = 91%, specificity = 98%, positive predictive value = 94%, and negative predictive value = 97%). Conclusion. A decline in the preoperative PTH level of 70% or greater at 1 hour following total thyroidectomy appears to be a reliable predictor of patients at risk of developing hypocalcemia. By allowing thyroid surgeons to identify these patients in the early postoperative period, calcium supplementation can be initiated sooner.

Cardiac ventricular trabeculae are widely used in the study of cardiac muscle function, primarily because their myocytes are axially-aligned. However, their collagen content has not been rigorously determined. In particular, it is unknown whether the content of collagen differs between specimens originating from the left (LV) and right (RV) ventricles and whether, indeed, either corresponds to the collagen content of the ventricular walls themselves. In order to redress this deficit of knowledge, we have used the techniques of fluorescence confocal microscopy and environmental scanning electron microscopy to quantify the proportion of perimysial collagen comprising the cross-sectional area of trabeculae carneae. In trabeculae from both the RV and LV of adult rat hearts, collagen may occupy as little as 1% or as much as 100% of the cross-section. For specimens of dimensions typically used experimentally, there was no difference in average collagen content (6.03 ± 5.14%, n = 33) of preparations from the two ventricles.

In a two-year carcinogenicity study with administration of high doses of the partial nicotinic agonist varenicline (recently approved for smoking cessation), mediastinal hibernomas occurred in three male rats. To investigate potential mechanisms for partial and full nicotinic agonists to contribute to development of hibernomas, the effects of nicotine on rat brown adipose tissue (BAT) were studied. Male and female rats were administered nicotine at doses of 0, 0.3, and 1 mg/kg subcutaneously for fourteen days. Intrathoracic (mediastinal periaortic and mediastinal perithymic) BAT and interscapular BAT were examined microscopically, and determinations of uncoupling protein-1 (UCP-1) expression and norepinephrine (NE) content were made. Additionally, NE turnover was measured in mediastinal periaortic and perithymic BAT. Nicotine (1 mg/kg) administration resulted in decreased vacuolation only in mediastinal periaortic and mediastinal perithymic BAT of males and elevated UCP-1 in mediastinal periaortic BAT of males and females. Increased NE content occurred only in mediastinal periaortic BAT of males given 0.3 and 1 mg/kg doses, whereas NE turnover was decreased in both males and females given 1 mg/kg. Together, these data demonstrate that nicotine primarily affects mediastinal BAT in male rats, consistent with the gender and location of the hibernomas observed in the two-year carcinogenicity study.

Changes in heart geometry and microstructural remodelling of myocardium are pathological processes that occur in heart failure (HF). The combination of effects often leads to compromised mechanical function of the left ventricle (LV). We have developed an image-driven constitutive modelling framework, which integrates subject-specific geometric data and microstructural organisation of the myocardial tissue, in order to investigate the mechanisms of heart function in health and disease. In this study, we investigated the effect of myocardial microstructural remodelling on passive mechanical function of the LV during the progression of hypertension-induced HF. We constructed finite element models of the LV using geometric data derived from in vivo magnetic resonance images of healthy and failing rat hearts at both 14-months and 24-months of age. By incorporating subject-specific LV geometries and parameters that directly reflect the tissue microstructure, we demonstrated that a single set of fitted constitutive parameters could reproduce the observed LV chamber compliance curves in all four cases (healthy and diseased hearts at 14-months and 24-months). This study highlights the important role that remodelling of myocardial microstructure plays in the mechanics of the failing heart.

The McGill Thyroid Nodule Score (MTNS) is a scoring system devised to help physicians to assess the preoperative risk that a thyroid nodule is malignant. It uses 22 different known risk factors for thyroid cancer (radiation exposure, microcalcifications on ultrasound, positive HBME-1 stain on biopsy, etc.) and attributes a percentage risk that the nodule is malignant. Recently, preoperative thyroglobulin (Tg) levels have been shown to correlate with the risk of malignancy. The aim of this study was to incorporate Tg levels into the already established MTNS.This is a retrospective analysis of 184 thyroidectomy patients at the McGill University Thyroid Cancer Center. Patients with preoperative Tg levels were included in the study, and patients with incidental papillary microcarcinoma without extrathyroidal extent on final pathology were excluded. MTNS scores were calculated for all patients. Preoperative Tg levels of 75 ng/mL added one point to the MTNS, and levels of 187.5 ng/mL added two points. The new system is named MTNS+.Malignancy rates were calculated for each MTNS+ score. Patients with a score of 0-1 were5% at risk of malignancy. The malignancy rate for scores of 2-3 was 14.29%, followed by 28.95% for scores of 4-6, 32.65% for scores of 7-8, 64.86% for scores of 9-11, 71.43% for scores of 12-14, 78.57% for scores of 15-18, and 92.31% for scores of 19-22. All patients (five of five) with an MTNS+ score of 23 or more had a malignant final pathology result. Patients with scores greater than eight had a relative risk of 2.5 [CI 1.79-3.49] of malignancy compared to patients with lower scores. MTNS+ showed good specificity at higher scores, with 89%, 96%, and 100% at scores above 11, 14, and 20 respectively. Compared to MTNS, adding Tg levels did not improve positive predictive values (PPV) or specificity, but improved sensitivity by 7.89% for scores greater than eight, and by up to 10.48% for scores greater than seven.This study shows that adding Tg to the MTNS increases the sensitivity of this scoring system. Moreover, it suggests that a combined scoring system such as the MTNS+ can accurately stratify the risk of well-differentiated malignancy in patients with thyroid nodules.

Computer models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. We have used novel techniques to build a structurally-detailed, image-based model of 3-D atrial anatomy. A volume image of the atria from a normal sheep heart was acquired using serial surface macroscopy, then smoothed and down-sampled to 50 μm(3) resolution. Atrial surface geometry was identified and myofiber orientations were estimated throughout by eigen-analysis of the 3-D image structure tensor. Sinus node, crista terminalis, pectinate muscle, Bachman's bundle, and pulmonary veins were segmented on the basis of anatomic characteristics. Heterogeneous electrical properties were assigned to this structure and electrical activation was simulated on it at 100 μm(3) resolution, using both biophysically-detailed and reduced-order cell activation models with spatially-varying membrane kinetics. We confirmed that the model reproduced key features of the normal spread of atrial activation. Furthermore, we demonstrate that vulnerability to rhythm disturbance caused by structural heterogeneity in the posterior left atrium is exacerbated by spatial variation of repolarization kinetics across this region. These results provide insight into mechanisms that may sustain paroxysmal atrial fibrillation. We conclude that image-based computer models that incorporate realistic descriptions of atrial myofiber architecture and electrophysiologic properties have the potential to analyse and identify complex substrates for atrial fibrillation.

The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodeling. Corresponding changes in three-dimensional organization of cardiac extracellular matrix have not been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and morphological data, brain natriuretic peptide levels, and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure, and decompensated HF. Passive left ventricular (LV) pressure-volume relationships were determined in vitro. Transmural specimens from the anterior LV free wall were imaged using extended-volume confocal microscopy, and three-dimensional myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 mo and increased progressively thereafter. However, it was less than in controls for filling pressures

Atrial fibrillation is the most common cardiac arrhythmia. It is prevalent in the elderly and contributes to mortality in congestive heart failure. Computer models of atrial electrical activation that incorporate realistic structure provide a means of investigating the mechanisms that initiate and maintain reentrant atrial arrhythmia. We are extending computational and experimental techniques that are well established in our laboratory to develop a detailed structure-based model of atrial electrical function. The 3D geometry of the atria and veno-atrial junctions is reconstructed from magnetic resonance images and detailed structure from specific regions of the atria is acquired using a semi-automated extended-volume imaging system. As an example of our approach, we present a reconstruction of the pig right atrial appendage (RAA), including the pectinate muscles (PM) and crista terminalis (CT). The RAA was embedded in wax and the block surface was serially etched, stained and imaged, then removed using an ultramiller to produce a uniformly-spaced image stack. Tissue was segmented and connected voxels were selected using a 3D region-growing algorithm to construct RAA geometry. Electrical activity has been modeled on this structure using the Courtemanche atrial cell activation model. A bidomain formulation was used employing a grid-based finite element solver. The RAA was activated by applying a stimulus (150 microA/mm3, 5 ms) to the 27 grid points at the top of the CT. Despite the complex structure of the PM, RAA activation was relatively uniform.

There is strong support for the view that the ventricular myocardium has a laminar organization in which myocytes are grouped into branching layers separated by cleavage planes. However, understanding of the extent and functional implications of this architecture has been limited by the lack of a systematic three-dimensional description of the organization of myocytes and associated perimysial collagen. We imaged myocytes and collagen across the left ventricular wall at high resolution in seven normal rat hearts using extended volume confocal microscopy. We developed novel reconstruction and segmentation techniques necessary for the quantitative analysis of three-dimensional myocyte and perimysial collagen organization. The results confirm that perimysial collagen has an ordered arrangement and that it defines a laminar organization. Perimysial collagen is composed of three distinct forms: extensive meshwork on laminar surfaces, convoluted fibers connecting adjacent layers, and longitudinal cords. While myolaminae are the principal form of structural organization throughout most of the wall, they are not seen in the subepicardium, where perimysial collagen is present only as longitudinal cords.

Simulations of cardiac electrical activity are generally computed in idealized or generic domains. We have developed a semi-automated technique for imaging an extended volume of cardiac ventricular tissue at a resolution of approximately 1 microm, and constructing from those images a geometric and structural model with 10 microm resolution suitable for solving the bidomain equations. This technique enables experimental modeling and computer simulation to be integrated by constructing a tissue-specific structural model in less than one week. We demonstrate the use of this procedure applied to a sample of rat ventricle.

Significant tissue structures exist in cardiac ventricular tissue, which are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhythmogenesis, and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modeling. Our models, which can incorporate ion channel models at the cell level into the reaction-diffusion equations at the tissue level, have enabled us to consider key hypotheses regarding discontinuous activation.

One of the main limitations in using inverse methods for non-invasively imaging cardiac electrical activity in a clinical setting is the difficulty in readily obtaining high-quality data sets to reconstruct accurately a patient-specific geometric model of the heart and torso. This issue was addressed by investigation into the feasibility of using a pseudo-3D ultrasound system and a hand-held laser scanner to reconstruct such a model. This information was collected in under 20 min prior to a catheter ablation or pacemaker study in the electrophysiology laboratory. Using the models created from these data, different activation field maps were computed using several different inverse methods. These were independently validated by comparison of the earliest site of activation with the physical location of the pacing electrodes, as determined from orthogonal fluoroscopy images. With an estimated average geometric error of approximately 8 mm, it was also possible to reconstruct the site of initial activation to within 17.3 mm and obtain a quantitatively realistic activation sequence. The study demonstrates that it is possible rapidly to construct a geometric model that can then be used non-invasively to reconstruct an activation field map of the heart.

The ability to accurately construct a geometric representation of the heart and torso is a critical component for electrocardiographic inverse algorithms. Typically geometric models have been constructed using data acquired from imaging modalities such as MRI and CT. We propose a system where the torso surface geometry is obtained using a laser scanning device and the heart geometry is obtained using three-dimensional ultrasound.

The clinical assessment of cardiac electrical function is usually performed by human interpretation of 12-lead ECG recordings. We investigate the use of mathematical models to obtain a quantitative electrical image from high-density ECG recordings. The process of modeling the electrical activity at the (continuum) cell level through to the torso surface, while maintaining a continuous path for current flow is presented. This provides a basis for the interpretation of ECG signals the so-called inverse problem of electrocardiography. The techniques used to solve the inverse problem are presented and the model is used in a clinical setting for validation purposes.

Lymphangiomas of the tongue are relatively uncommon, and traditional treatment modalities carry a high failure rate. We present here a case report of effective treatment of lymphangioma circumscriptum of the oral tongue using radiofrequency coblation, while including a review of the current literature.

Iatrogenic foreign bodies in the aerodigestive tract are exceedingly rare, as implied by the paucity of reported cases in the literature. To date, only 10 such cases have been published and have mostly involved the aspiration of either respiratory care equipment or parts of sterilization instruments that had become lodged within these devices [1–7]. Amongst these exists a small number of reportings of objects retained within laryngeal mask airways (LMA) and subsequently deposited into the larynx [3]. In this article we present an unusual case of a plastic electrocardiogram-lead cover introduced inadvertently into the vallecula of a teenager upon insertion of a LMA, and the subsequent course that culminated in removal under general anesthetic. This case illustrates the need for routine prevention strategies when using LMA ventilation.

Rationale The preclinical characterization of a series of aryloxypyridine amides has identified JNJ-39220675 ((4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone) as a high-affinity histamine H3 receptor antagonist and a candidate for further drug development particularly in the treatment of alcohol-related behaviors.