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Nuclear shape alteration in ocular tissues, which can be used as a metric for overall cell deformation, may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. The biomechanics of iris tissue is of particular interest in the study of primary angle-closure glaucoma. As the first step towards understanding the mutual role of the biomechanics and deformation of the iris on the activity of its constituent stromal cells, we conducted an ex-vivo study in freshly excised porcine eyes. Iris deformation was achieved by activating the constituent smooth muscles of the iris. Pupillary responses were initiated by inducing miosis and mydriasis, and the irides were placed in a fixative, bisected, and sliced into thin sections in a nasal and temporal horizontal orientation. The tissue sections were stained with DAPI for nucleus, and z-stacks were acquired using confocal microscopy. Images were analyzed to determine the nuclear aspect ratio (NAR) using both three-dimensional (3D) reconstructions of the nuclear surfaces as well as projections of the same 3D reconstruction into flat two-dimensional (2D) shapes. We observed that regardless of the calculation method (i.e., one that employed 3D surface reconstructions versus one that employed 2D projected images) the NAR increased in both the miosis group and the mydriasis group. Three-dimensional quantifications showed that NAR increased from 2.52 ± 0.96 in control group to 2.80 ± 0.81 and 2.74 ± 0.94 in the mydriasis and miosis groups, respectively. Notwithstanding the relative convenience in calculating the NAR using the 2D projected images, the 3D reconstructions were found to generate more physiologically realistic values and, thus, can be used in the development of future computational models to study primary angle-closure glaucoma. Since the iris undergoes large deformations in response to ambient light, this study suggests that the iris stromal cells are subjected to a biomechanically active micro-environment during their in-vivo physiological function.

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The tricuspid valve is an atrioventricular valve that prevents blood backflow from the right ventricle into the right atrium during ventricular contractions. It is important to study mechanically induced microstructural alterations in the tricuspid valve leaflets, as this aids both in understanding valvular diseases and in the development of new engineered tissue replacements. The structure and composition of the extracellular matrix (ECM) fiber networks are closely tied to an overall biomechanical function of the tricuspid valve. In this study, we conducted experiments and implemented a multiscale modeling approach to predict ECM microstructural changes to tissue-level mechanical responses in a controlled loading environment. In particular, we characterized a sample of a porcine anterior leaflet at a macroscale using a biaxial mechanical testing method. We then generated a three-dimensional finite element model, to which computational representations of corresponding fiber networks were incorporated based on properties of the microstructural architecture obtained from small angle light scattering. Using five different biaxial boundary conditions, we performed iterative simulations to obtain model parameters with an overall R2 value of 0.93. We observed that mechanical loading could markedly alter the underlying ECM architecture. For example, a relatively isotropic fiber network (with an anisotropy index value α of 28%) became noticeably more anisotropic (with an α of 40%) when it underwent mechanical loading. We also observed that the mechanical strain was distributed in a different manner at the ECM/fiber level as compared to the tissue level. The approach presented in this study has the potential to be implemented in pathophysiologically altered biomechanical and structural conditions and to bring insights into the mechanobiology of the tricuspid valve. STATEMENT OF SIGNIFICANCE: Quantifying abnormal cellar/ECM-level deformation of tricuspid valve leaflets subjected to a modified loading environment is of great importance, as it is believed to be linked to valvular remodeling responses. For example, developing surgical procedures or engineered tissue replacements that maintain/mimic ECM-level mechanical homeostasis could lead to more durable outcomes. To quantify leaflet deformation, we built a multiscale framework encompassing the contributions of disorganized ECM components and organized fibers, which can predict the behavior of the tricuspid valve leaflets under physiological loading conditions both at the tissue level and at the ECM level. In addition to future in-depth studies of tricuspid valve pathologies, our model can be used to characterize tissues in other valves of the heart.

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PURPOSE: This study was conducted to investigate changes in intraocular pressure (IOP) in the presence of intravitreal gas bubbles in individuals who travel through subsea tunnels. METHODS: Using a mathematical model, we simulated alterations in ocular globe shape, aqueous humor flow, volume of intravitreal gas bubbles, and IOP due to elevation changes during travel through subsea tunnels. We simulated five tunnels with different features as case studies. The role of key modeling parameters was further evaluated in a parametric study. RESULTS: In three out of the five simulated tunnels (i.e., Seikan Tunnel, Bomlafjord Tunnel, and the Atlantic Ocean Tunnel), the patients were potentially at risk at lower portions of the tunnels since the IOP dropped to values less than 5 mm Hg, the clinical threshold for ocular hypotony. During ascent, the IOP increased to the normal value of 15 mm Hg and in some cases to higher values (e.g., a peak value of 22 mm Hg in Seikan Tunnel). CONCLUSIONS: Our model predicted that in the presence of intravitreal gas bubbles, the IOP could drop to extremely low values when patients descend to lower elevations in some tunnels. Such low IOP values could cause bleeding and/or retinal detachment. Since many factors (e.g., tunnel specifications and/or patient-specific characteristics) could affect the IOP during subsea travel, caution (beyond avoiding airplane flights) should be taken in advising patients about travel restrictions following intravitreal gas injections. TRANSLATIONAL RELEVANCE: Our findings highlight the potential risk for hypotony in the presence of intravitreal gas bubbles during subsea travels.

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Rapid advancements in the multidisciplinary field of biomedical engineering (BME) require competitive engineers with skill sets in a broad range of subjects including biology, physiology, mechanics, circuits, and programming. Accordingly, such a need should be reflected in the training of BME students. Among those skills, computer programming is an essential tool that is used in a wide variety of applications. In this paper, we have provided our experience in incorporating project-based learning, a promising approach in active learning, for teaching computer programming to BME students. We describe a low-cost method for using physical, hands-on computing that directly relates to BME. Additionally, we detail our efforts to teach multiple programming languages in one semester and provide a detailed analysis of the outcomes. We also provide basic materials for other instructors to adapt to fit their own needs.

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Quantifying mechanically-induced changes in the tricuspid valve extracellular matrix (ECM) structural components, e.g. collagen fiber spread and distribution, is important as it determines the overall macro-scale tissue responses and subsequently its function/malfunction in physiological/pathophysiological states. For example, functional tricuspid regurgitation, a common tricuspid valve disorder, could be caused by elevated right ventricular pressure due to pulmonary hypertension. In such patients, the geometry and the normal function of valve leaflets alter due to chronic pressure overload, which could cause remodeling responses in the ECM and change its structural components. To understand such a relation, we developed an experimental setup and measured alteration of leaflet microstructure in response to pressure increase in porcine tricuspid valves using the small angle light scattering technique. The anisotropy index, a measure of the fiber spread and distribution, was obtained and averaged for each region of the anterior, posterior, and septal leaflet using four averaging methods. The average anisotropy indices (mean ±â€¯standard error) in the belly region of the anterior, posterior, and septal leaflets of non-pressurized valves were found to be 12 ±â€¯2%, 21 ±â€¯3% and 12 ±â€¯1%, respectively. For the pressurized valve, the average values of the anisotropy index in the belly region of the anterior, posterior, and septal leaflets were 56 ±â€¯5%, 39 ±â€¯7% and 32 ±â€¯5%, respectively. Overall, the average anisotropy index was found to be higher for all leaflets in the pressurized valves as compared to the non-pressurized valves, indicating that the ECM fibers became more aligned in response to an increased ventricular pressure. STATEMENT OF SIGNIFICANCE: Mechanics plays a critical role in development, regeneration, and remodeling of tissues. In the current study, we have conducted experiments to examine how increasing the ventricular pressure leads to realignment of protein fibers comprising the extracellular matrix (ECM) of the tricuspid valve leaflets. Like many other tissues, in cardiac valves, cell-matrix interactions and gene expressions are heavily influenced by changes in the mechanical microenvironment at the ECM/cellular level. We believe that our study will help us better understand how abnormal increases in the right ventricular pressure (due to pulmonary hypertension) could change the structural architecture of tricuspid valve leaflets and subsequently the mechanical microenvironment at the ECM/cellular level.

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