Circumferential Axis Research Articles

An optical system for cellular mechanostimulation in 3D hydrogels

We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca2+ signaling following exposure to an impulsive mechanical stimulus provided by a single 250 µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca2+ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy. Statement of significanceCurrently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.

Fabrication and mechanical characterization of near field electrospun bioresorbable vascular grafts with fibrous architecture mimicking the arterial extracellular matrix

Cardiovascular disease, arteriosclerosis, is characterized by the thickening of blood vessel (arteries) walls restricting blood flow and is a global health problem. One treatment option is a surgical procedure utilizing an autologous or synthetic vascular graft to bypass or replace the diseased arterial segment. The goal of this study was to fabricate and mechanically characterize near field electrospun bioresorbable vascular grafts with a fibrous architecture that mimics the arterial extracellular matrix. Polydioxanone vascular constructs with circumferential fiber alignment angles of 15°/75° and 30°/60° (0° representing circumferential fiber alignment) were fabricated using a custom built near-field electrospinning (NFES) system. The vascular construct mechanical properties were compared to the saphenous vein (SV) and internal mammary artery (IMA) through longitudinal and circumferential uniaxial mechanical testing, suture retention, and burst pressure evaluations. The results demonstrated that the 15°/75° templates were closest to mimicking the native vessel target properties as compared to the 30°/60°; however, neither of the vascular template designs achieved or exceeded all the target values. For the ultimate tensile strength, both the constructs met the SV value on the circumferential axis (2.61 MPa) and the IMA value on the longitudinal axis (4.3 MPa). In terms of suture retention, the 15°/75° template was the only construct that was in the IMA and SV targeted range of 138–200 gf. Finally, the burst pressure testing results indicated that neither of the vascular constructs achieved the level of the SV or IMA (1600–3196 mmHg), however, the 15° constructs were within the lower error of the SV. In conclusion, with further design modifications, NFES constructs have demonstrated promise as small-diameter vascular grafts by mimicking native arterial architecture and mechanical properties.

Effect of Ultraviolet Radiation on the Enzymolytic and Biomechanical Profiles of Abdominal Aortic Adventitia Tissue.

The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without treatment. The aim of this study is to analyze the role of aortic adventitial collagen photocrosslinking by UV-A irradiation on the biomechanical profile of the aortic wall. This experimental study is structured in two parts: the first part includes in vitro uniaxial biomechanical evaluation of porcine adventitial tissue subjected to either short-term elastolysis or long-term collagenolysis in an attempt to duplicate two extreme situations as putative stages of aneurysmal degeneration. In the second part, we included biaxial biomechanical evaluation of in vitro human abdominal aortic adventitia and human AAA adventitia specimens. Biomechanical profiles were examined for porcine and human aortic tissue before and after irradiation with UV-A light (365 nm wavelength). On the porcine aortic sample, the enhancing effect of irradiation was evident both on the tissue subjected to elastolysis, which had a high collagen-to-elastin ratio, and on the tissue subjected to prolonged collagenolysis despite being considerably depleted in collagen. Further, the effect of irradiation was conclusively demonstrated in the human adventitia samples, where significant post-irradiation increases in Cauchy stress (longitudinal axis: p = 0.001, circumferential axis: p = 0.004) and Young's modulus (longitudinal axis: p = 0.03, circumferential axis: p = 0.004) were recorded. Moreover, we have a stronger increase in the strengthening of the AAA adventitia samples following the exposure to UV-A irradiation (p = 0.007) and a statistically significant but not very important increase (p = 0.021) regarding the stiffness in the circumferential axis. The favorable effect of UV irradiation on the strength and stiffness of degraded aortic adventitia in experimental situations mimicking early and later stages of aneurysmal degeneration is essential for the development and potential success of procedures to prevent aneurysmal ruptures. The experiments on human normal and aneurysmal adventitial tissue confirmed the validity and potential success of a procedure based on exposure to UV-A radiation.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Ex-vivo Mechanical Augmentation of Human Saphenous Vein Graft By UV-A Irradiation in Emergency Vascular Reconstruction – Preliminary Results

Abstract Introduction In vascular reconstruction in arterial trauma, ruptured abdominal aortic aneurysm or ruptured aneurysmal arteriovenous fistula, the challenge no longer lies in the surgical procedure itself, but rather the prevention of intimal hyperplasia, thrombosis and aneurysm formation, in parallel with extending as long as possible the patency of the grafts. The aim of this study is to present the preliminary findings of a novel non-ionizing radiation-based therapeutic method for stabilizing and strengthening the extracellular matrix of the venous wall, improving the biomechanical profile of the autologous graft used in myocardial and lower limb revascularization. Material and methods We developed the protocol and method for UV-A irradiation as a new method of mechanical augmentation of the resistance structure of the venous graft. Samples of the superficial femoral artery, superficial femoral vein, and great saphenous vein (GSV) were extracted from a 58-year-old patient who underwent above-the-knee amputation, and were prepared in 5 × 5 cm2 patches. Additionally, we analyzed the samples biomechanically biaxially with the BioTester® 5000, in which we established a 25% equibiaxial stretch. The GSV sample was also treated by UV-A irradiation after being kept in riboflavin 5′-phosphate monosodium salt for 30 min. Results After UV-A treatment of the GSV wall, we observed an important increase of Cauchy stress from 82 kPa to 131 kPa in the longitudinal axis and from 66 kPa to 115 kPa in the circumferential axis. Young’s modulus also changed after treating the GSV wall from 0.564 MPa to 1.218 MPa (longitudinal) and from 0.397 MPa to 0.709 MPa (circumferential). As a result of the therapy, we observed a considerable similarity of the mechanical behavior of the GSV wall to that of the artery wall. Conclusion The photocrosslinking of collagen fibbers at the vein graft adventitia hardens and stiffens the venous wall, making it behave like the arterial wall after treatment. These preliminary ex vivo results on human vascular tissue may serve as the foundation for the development of new treatment approaches utilizing mechanical augmentation of the vein grafts.

Relationships in Shark Skin: Mechanical and Morphological Properties Vary between Sexes and among Species.

Shark skin is a composite of mineralized dermal denticles embedded in an internal collagen fiber network and is sexually dimorphic. Female shark skin is thicker, has greater denticle density and denticle overlap compared to male shark skin, and denticle morphology differs between sexes. The skin behaves with mechanical anisotropy, extending farther when tested along the longitudinal (anteroposterior) axis but increasing in stiffness along the hoop (dorsoventral or circumferential) axis. As a result, shark skin has been hypothesized to function as an exotendon. This study aims to quantify sex differences in the mechanical properties and morphology of shark skin. We tested skin from two immature male and two immature female sharks from three species (bonnethead shark, Sphyrna tiburo; bull shark, Carcharhinus leucas; silky shark, Carcharhinus falciformis) along two orientations (longitudinal and hoop) in uniaxial tension with an Instron E1000 at a 2 mm s-1 strain rate. We found that male shark skin was significantly tougher than female skin, although females had significantly greater skin thickness compared to males. We found skin in the hoop direction was significantly stiffer than the longitudinal direction across sexes and species, while skin in the longitudinal direction was significantly more extensible than in the hoop direction. We found that shark skin mechanical behavior was impacted by sex, species, and direction, and related to morphological features of the skin.

Performance analysis of journal bearing having surface waviness operating under misaligned condition

In this present study, the effect of surface waviness on the performance of journal bearing operating in misaligned conditions has been investigated. The journal’s misaligned conditions in the present analysis are taken about the circumferential, the axial, and both axes. For computing the pressure of lubricant inside the bearing, the finite element method has been applied to solve the Reynolds equation and thus static parameters are obtained. The static parameters, that is, load carrying capacity and coefficient of friction are evaluated at different waviness variables and are compared with misaligned journal bearing without surface waviness. It is observed that misalignment considered in both axes has the most severe effect on static performance parameters as compared to misalignment only in the circumferential or axial axis. With the increase in circumferential waviness number up to n = 5, the load-carrying capacity increases, and the coefficient of friction decreases under high eccentricity ratios. Change in waviness amplitude also impacts the bearing performance. Axial waviness always deteriorates the bearing performance. Combined waviness increases the load carrying capacity and decreases the coefficient of friction when circumferential waviness number n = 5 and axial waviness number m = 2. The highest performance enhancement ratio is attained at an eccentricity ratio of 0.8 with a circumferential waviness number n of 5, axial waviness number m of 2, and dimensionless waviness amplitude [Formula: see text] of 0.075.

The Tetrahymena bcd1 mutant implicates endosome trafficking in ciliate, cortical pattern formation.

Ciliates, such as Tetrahymena thermophila, evolved complex mechanisms to determine both the location and dimensions of cortical organelles such as the oral apparatus (OA: involved in phagocytosis) cytoproct (Cyp: for eliminating wastes) and contractile vacuole pores (CVPs: involved in water expulsion). Mutations have been recovered in Tetrahymena that affect both the localization of such organelles along anterior-posterior and circumferential body axes, and their dimensions. Here we describe BCD1, a ciliate pattern-gene that encodes a conserved beige-BEACH-domain containing protein a with possible PKA-anchoring activity. Similar proteins have been implicated in endosome trafficking, and are linked to human Chediak-Higashi syndrome and autism. Mutations in the BCD1 gene broaden cortical organelle domains as they assemble during pre-division development. The Bcd1 protein localizes to membrane pockets at the base of every cilium that are active in endocytosis. PKA activity has been shown to promote endocytosis in other organisms, so we blocked clathrin-mediated endocytosis (using 'dynasore') and inhibited PKA (using H89). In both cases, treatment produced partial phenocopies of the bcd1 pattern mutant. This study supports a model in which the dimensions of diverse cortical organelle assembly-platforms may be determined by regulated balance between constitutive exocytic delivery and PKA-regulated endocytic retrieval of organelle materials and determinants.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Inter-field strength agreement of cardiovascular magnetic resonance cine-derived strain and strain rate measures: a randomised study

Abstract Background Left ventricular (LV) strain and strain rate measurements can be derived from routinely acquired cardiovascular magnetic resonance (CMR) cine images by feature tracking techniques. However, the inter-field strength agreement of strain measurements derived from these techniques is not known. We hypothesised that there would be excellent inter-field strength agreement (between 1.5 and 3 Tesla [T]) for the measurement of global strain and strain rate derived from cine imaging. Methods Prospective, randomised cross-over observational study. Healthy volunteers each underwent CMR scans at 1.5T and 3T within 30 minutes on the same day in a randomised order. Retrospectively ECG gated, short and long-axis balanced steady state free precession cine images were obtained using standardised acquisition parameters at both field strengths. Two software packages were used to derive LV global longitudinal, circumferential and long and short axis radial systolic strain, peak systolic, early diastolic and late diastolic strain rates. All strain values are expressed as positive numbers. Results Twenty-two subjects (mean age 36±12 years; 45% male) were studied. No differences in heart rate and blood pressure measurements during scanning were observed between field strengths. The abstract figure shows an example of strain analysis and Bland-Altman plots for global longitudinal and circumferential strain. Minimal bias was seen in all strain and strain rate measurements between field strengths using the first software package. Strain and strain rate values derived from long axis images (longitudinal and long axis radial) showed poor to fair agreement (intraclass correlation co-efficient (ICC) range 0.39–0.71), whereas measures derived from short axis images (circumferential and short axis radial) showed good to excellent agreement between field strengths (ICC range 0.78–0.91). Similar results were observed with the second software package, though the differences in agreement between long and short axis derived measures were less pronounced. Conclusion Longitudinal strain and strain rate measures derived from CMR feature tracking have poor inter-field strength agreement between 1.5T and 3T. By contrast, agreement of circumferential and short axis radial strain and strain rate measurements at 1.5T and 3T is good. These results need to be considered when assessing strain at different field strengths. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): United Kingdom National Institute for Health Research

Analysis of Clinical Efficacy of Clearing Heat and Dispelling Paralysis Soup in the Treatment of Osteoarthritis of the Knee Joint and Its Effect on Patients' Motor Function.

Objective To investigate the effects of clearing heat and dispelling paralysis soup for osteoarthritis of the knee joint on the motor function of the knee joint and the level of inflammation of the organism in patients. Methods One hundred and sixteen patients with knee osteoarthritis admitted from January 2020 to May 2021 were selected and randomly divided into 2 groups, 58 cases in the control group were treated with loxoprofen sodium dispersible tablets, and 58 cases in the experimental group were treated with Qinghe dispel paralysis soup on the basis of the control group and the patients' balance ability analysis, gait parameter change analysis, VAS, JOA, AIMS2-SF scale assessment, and serum index. The treatment effects of the two treatment regimens were analyzed by testing. Results The anterior-posterior axis, left-right axis, A2-A6, A4-A8, and circumferential axis of the experimental group were lower than those of the control group after treatment (P < 0.05); the step length of the experimental group was higher than that of the control group after treatment (P < 0.05), and there were no significant differences in step speed, double-support phase, and step width (P > 0.05), but both groups improved significantly compared with those before treatment (P < 0.05); the VAS score of the experimental group was lower than that of the control group after treatment. The VAS scores of the experimental group were lower than those of the control group, and the scores of JOA and AIMS2-SF were higher than those of the control group (P < 0.05); the levels of TIMP-1 in the experimental group were higher than those in the control group, and the levels of TNF-α, TLR4, MMP-3, and IL-1 were lower than those in the control group after treatment (P < 0.05); there was no significant difference in the incidence of adverse reactions between the two groups during treatment (P > 0.05), and the efficiency of the experimental group was higher than that of the control group (P < 0.05). Conclusion Combined treatment with Qinghe dispel paralysis soup can better promote the recovery of balance, improve motor ability, and reduce the development of inflammation in the organism, with high safety and effectiveness.

Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats

After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n = 46) and adults (8–10 weeks old, n = 20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n = 15) and sham rats (n = 14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p = 0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9 kPa vs 274.2 kPa, p = 0.7847), longitudinal modulus (269.3 kPa vs 277.1 kPa, p = 0.7435), and maximum shear stress (3.30 kPa vs 3.95 kPa, p = 0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n = 7) exhibited profound LV wall thinning (p < 0.0001), chamber dilation (p = 0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p < 0.0001) compared to adult sham hearts (n = 7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5 kPa vs 180.0 kPa, p = 0.0111) and longitudinal axes (315.4 kPa vs 172.3 kPa, p = 0.0173), and also exhibited greater maximum shear stress (14.87 kPa vs 3.23 kPa, p = 0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.

Effect of an Axially Tilted Variable Stator Vane Platform on Penny Cavity and Main Flow

Abstract This paper presents the impact of an axially tilted variable stator vane (VSV) platform on penny cavity flow and passage flow, with the aid of both optical and pneumatic measurements in an annular cascade wind tunnel as well as steady computational fluid dynamics (CFD) analyses. Variable stator vanes in axial compressors require a clearance from the endwalls. This means that penny cavities around the vane platform are inevitable. Production and assembly deviations can result in a vane platform which is tilted about the circumferential axis. Penny cavity and main flow in geometries with and without platform tilting were compared in an annular cascade wind tunnel. Detailed particle image velocimetry (PIV) measurements were conducted inside the penny cavity and in the vane passage. Steady pressure and velocity data was obtained by two-dimensional multi-hole pressure probe traverses in the inflow and the outflow. Furthermore, pneumatic measurements were carried out using pressure taps inside the penny cavity. Additionally, oil flow visualization was conducted on the airfoil, hub, and penny cavity surfaces. Steady CFD simulations have been benchmarked against experimental data. The results show that tilting the vane platform reduces the penny cavity leakage mass flow. By decreasing penny cavity leakage, platform tilting also affects the passage flow where it leads to a reduced turbulence level and total pressure loss in the leakage flow region. In summary, the paper demonstrates the influence of penny platform tilting on cavity flow and passage flow and provides new insights into the mechanisms of penny cavity-associated losses.

Abstract No. 225 Venous large animal model for stenosis, thrombosis, and chronic occlusion: short-term results, with biomechanical analysis

Angiographic and biomechanical characterization of an ovine venous stenosis/occlusion model developed for studying translational interventions in venous occlusive disease. Unilateral iliac vein stenosis was created in six adult sheep using established endovenous radiofrequency (RF) ablation technique. Two sheep underwent short-segment RF ablation with the goal of creating chronic stenoses. Four sheep underwent long-segment RF ablation with the goal of inducing thrombosis/occlusion. Ultrasound and angiographic assessment was performed at baseline, immediately after venous stenosis creation, and prior to euthanasia at 2-week follow-up. Vein samples were immediately harvested for biomechanical assessment. Uniaxial longitudinal and circumferential tensile testing was performed with a custom mounting apparatus at a crosshead speed of 4 mm/min (MTS Criterion, Eden Prairie, MN). At 2-week follow-up venogram, the short-segment group (length: 11.5 ± 3.5 mm; stenosis: 64.0 ± 6.0%) showed stable stenosis without thrombosis in all animals. The long-segment group (length: 61.1 ± 12.2 mm; stenosis: 76.4 ± 3.3%) showed complete iliac occlusion/thrombosis with collateralization in all animals. Gross vein specimens showed thickened venous wall (0.28 ± 0.04 mm; contralateral normal control: 0.16 ± 0.02 mm; P< 0.05) and early scar tissue formation in all samples as well as soft non-adherent thrombi in the occlusion samples. Both stenotic and occlusive vein samples showed higher stiffness compared to the contralateral normal controls (P< 0.05), and higher stiffness in the longitudinal compared to the circumferential axis (P< 0.05). RF ablation can produce stable short-segment venous stenosis and long-segment thrombosis/occlusion in short-term survival. Tensile testing showed increased venous wall stiffness, replicating expected post-thrombotic biomechanical changes. Further studies are underway for biomechanical and histologic characterization of chronic fibrosis created in this large animal model. Once validated, this large animal model can be used for studying venous stenosis, thrombosis, chronic occlusion and their associated interventions.

Gut innervation and enteric nervous system development: a spatial, temporal and molecular tour de force.

During embryonic development, the gut is innervated by intrinsic (enteric) and extrinsic nerves. Focusing on mammalian ENS development, in this Review we highlight how important the different compartments of this innervation are to assure proper gut function. We specifically address the three-dimensional architecture of the innervation, paying special attention to the differences in development along the longitudinal and circumferential axes of the gut. We review recent information about the formation of both intrinsic innervation, which is fairly well-known, as well as the establishment of the extrinsic innervation, which, despite its importance in gut-brain signaling, has received much less attention. We further discuss how external microbial and nutritional cues or neuroimmune interactions may influence development of gut innervation. Finally, we provide summary tables, describing the location and function of several well-known molecules, along with some newer factors that have more recently been implicated in the development of gut innervation.

Systolic dysfunction by two-dimensional speckle tracking echocardiography in dogs with parvoviral enteritis

Introduction/objectivesParvoviral enteritis (PVE) can cause either primary or secondary myocardial injury; the latter is associated with systemic inflammatory response syndrome and sepsis. Strain (St) and strain rate (SR) are relatively new speckle tracking echocardiographic (STE) variables used to assess myocardial function and are less influenced by preload and volume status than are conventional variables. The aim of this study was to evaluate systolic function in dogs with PVE using two-dimensional STE. AnimalsForty-five client-owned dogs were included. Materials and methodsDogs were classified into four groups: healthy (n = 9), PVE-mild (n = 15), PVE-severe (n = 13) and PVE-died (n = 8). Left ventricular global and segmental myocardial St and SR were assessed in radial, circumferential and longitudinal axes in the right parasternal transverse and apical 4-chamber views. In the circumferential and longitudinal axes, the value of each segment was determined separately at the endocardial and epicardial levels. ResultsCompared to healthy animals, all dogs with PVE showed significantly impaired St and SR values, mainly for PVE-severe and PVE-died groups. Moreover, the lowest SR value was observed in the circumferential axis at the mid-septal epicardial segment in the PVE-died group. For this variable, a cut-off value of 0.95 s−1 demonstrated 100% sensitivity and specificity for distinguishing between PVE-severe and PVE-died groups. ConclusionsIn the present study, all dogs with PVE developed systolic dysfunction, which was more severe in non-survivors. Assessment of St and SR in dogs with PVE might be clinically useful for evaluating haemodynamic status and developing suitable therapeutic strategies to improve prognosis.

Comparative biomechanics of hagfish skins: diversity in material, morphology, and movement

The baggy skins of hagfishes confer whole-body flexibility that enables these animals to tie themselves into knots without injury. The skin’s looseness is produced by a subcutaneous blood sinus that decouples the skin and body core and permits the core to contort dramatically without loading the skin in tension or shear. Hagfish skin represents a biological composite material comparable in strength and stiffness to the conventionally taut skins of other fishes. However, our understanding of hagfish skin is restricted to only one of 78 species: The Pacific hagfish Eptatretus stoutii. To determine if other hagfish share similar characteristics with E. stoutii, we measured material properties and compared histological data sets from the skins of four hagfish species: E. springeri, E. stoutii, Myxine glutinosa, and M. hubbsi. We also compared these material properties data with skins from the American eel, Anguilla rostrata. We subjected skin samples from all species to uniaxial tensile tests in order to measure strength, stiffness, extensibility, and toughness of skins stretched along longitudinal and circumferential axes. We also used a series of equibiaxial tensile tests on skin samples from E. stoutii, M. glutinosa, and A. rostrata to measure stiffness of skins simultaneously strained along both axes. Significant results of uniaxial and biaxial tests show that the skins from Eptatretus are anisotropic, being stiffer in the longitudinal axis, and more extensible than the isotropic skins of Myxine. Skins of A. rostrata were stiffer in the circumferential axis and they were stronger, tougher, and stiffer than all hagfish skins examined. The skins of Eptatretus are histologically distinct from Myxine skins and possess arrays of fibers that stain like muscle. These interspecific differences across hagfish skins show a phylogenetic pattern with knotting kinematics and flexibility; both genera belong to distinct but major subfamilies within the Myxinidae, and Eptatretus is known for creating and manipulating a greater diversity of knotting styles than Myxine.

Quantification of myocardial strain assessed by cardiovascular magnetic resonance feature tracking in healthy subjects\u2014influence of segmentation and analysis software

ObjectivesQuantification of myocardial deformation by feature tracking is of growing interest in cardiovascular magnetic resonance. It allows the assessment of regional myocardial function based on cine images. However, image acquisition, post-processing, and interpretation are not standardized. We aimed to assess the influence of segmentation procedure such as slice selection and different types of analysis software on values and quantification of myocardial strain in healthy adults.MethodsHealthy volunteers were retrospectively analyzed. Post-processing was performed using CVI42 and TomTec. Longitudinal and radialLong axis (LAX) strain were quantified using 4-chamber-view, 3-chamber-view, and 2-chamber-view. Circumferential and radialShort axis (SAX) strain were assessed in basal, midventricular, and apical short-axis views and using full coverage. Global and segmental strain values were compared to each other regarding their post-processing approach and analysis software package.ResultsWe screened healthy volunteers studied at 1.5 or 3.0 T and included 67 (age 44.3 ± 16.3 years, 31 females). Circumferential and radialSAX strain values were different between a full coverage approach vs. three short slices (− 17.6 ± 1.8% vs. − 19.2 ± 2.3% and 29.1 ± 4.8% vs. 34.6 ± 7.1%). Different analysis software calculated significantly different strain values. Within the same vendor, different field strengths (− 17.0 ± 2.1% at 1.5 T vs. − 17.0 ± 1.7% at 3 T, p = 0.845) did not influence the calculated global longitudinal strain (GLS), and were similar in gender (− 17.4 ± 2.0% in females vs. − 16.6 ± 1.8% in males, p = 0.098). Circumferential and radial strain were different in females and males (circumferential strain − 18.2 ± 1.7% vs. − 17.1 ± 1.8%, p = 0.029 and radial strain 30.7 ± 4.7% vs. 27.8 ± 4.6%, p = 0.047).ConclusionsMyocardial deformation assessed by feature tracking depends on segmentation procedure and type of analysis software. CircumferentialSAX and radialSAX depend on the number of slices used for feature tracking analysis. As known from other imaging modalities, GLS seems to be the most stable parameter. During follow-up studies, standardized conditions should be warranted.Trial registration Retrospectively registeredKey Points• Myocardial deformation assessed by feature tracking depends on the segmentation procedure.• Global myocardial strain values differ significantly among vendors.• Standardization in post-processing using CMR feature tracking is essential.

Supervised Machine Learning Segmentation and Quantification of Gastric Pacemaker Cells.

Interstitial Cells of Cajal (ICC) are specialized pacemaker cells that generate and actively propagate electrophysiological events called slow waves. Slow waves regulate the motility of the gastrointestinal tract necessary for digesting food. Degradation in the ICC network structure has been qualitatively associated to several gastrointestinal motility disorders. ICC network structure can be obtained using confocal microscopy, but the current limitations in imaging and segmentation techniques have hindered an accurate representation of the networks. In this study, supervised machine learning techniques were applied to extract the ICC networks from 3D confocal microscopy images. The results showed that the Fast Random Forest classification method using Trainable WEKA Segmentation outperformed the Decision Table and Naïve Bayes classification methods in sensitivity, accuracy, and F-measure. Using the Fast Random Forest classifier, 12 gastric antrum tissue blocks were segmented and variations in ICC network thickness, density and process width were quantified for the myenteric plexus ICC network (the primary pacemakers). Our findings demonstrated regional variation in ICC network density and thickness along the circumferential and longitudinal axis of the mouse antrum. An inverse relationship was observed in the distal and proximal antrum for density (proximal: 9.8±4.0% vs distal: 7.6±4.6%) and thickness (proximal: 15±3 μm vs distal: 24±10 μm). Limited variation in ICC process width was observed throughout the antrum (5±1 μm).Clinical Relevance- Detailed quantification of regional ICC structural properties will provide insights into the relationship between ICC structure, slow waves and resultant gut motility. This will improve techniques for the diagnosis and treatment of functional GI motility disorders.

Numerical Computation of Circumferential Waves in Cylindrical Curved Waveguides

We present a complex field general variational statement to study the waves propagating in the circumferential directions of cylindrical curved waveguides. A semi-analytical technique that has been applied on straight waveguides in the literature is reformulated to adapt to the circumferential directions and used for constructing the trial wavefunction in complex field. The method requires the waveguide to be analyzed to be geometrically and physically uniform along its circumferential axis; however, its circumferential cross-section can be arbitrarily complex. The formulation is verified using various examples, which were examined previously by other numerical or analytical solutions. Different cases were studied and comparisons with those published are also performed show the utility and advantages of present method.