A comparative evaluation of the effects of 635 nm laser on cell proliferation and osteogenic differentiation of buccal fat pad mesenchymal stem cells.

The purpose of this study was to evaluate the effects of 635 nm diode laser with different powers on undifferentiated mesenchymal stem cells obtained from buccal fat pad. Human buccal fat stem cells were cultured in DMEM containing 10% FBS, penicillin, and streptomycin under 5% CO2 and 95% humidity. Cells were cultured in 96-well plate and 24 h later, laser irradiation with 635 nm diode laser was performed in four groups of 200, 300, 400, and 500 mW powers in addition to the control group with the same energy density of 4 J/cm2. MTT and flow cytometry assay was performed to evaluate cell proliferation and viability on 2 and 4 days after irradiation. Alizarin red assay and real-time PCR (OPN, OCN, ALP, and RUNX-2 genes) was performed to evaluate osteogenic differentiation. According to the MTT assay, none of the mentioned powers of 635 nm diode laser had significant effect on cell proliferation. Cells irradiated with power of 400 mW and 500 mW significantly showed a greater number of necrotic cells compared to the control group in Day 4. Cells irradiated with 300 mW power significantly exhibited a greater amount of nodule formation compared to all groups. Results of this study indicated that 635 nm diode laser with energy density of 4 J/cm2 has a positive effect inducing osteogenic differentiation when applying with a power of 300 mW in buccal fat pad mesenchymal stem cells.

Integrating Deep Learning with Electronic Health Records for Early Glaucoma Detection: A Multi-Dimensional Machine Learning Approach.

BACKGROUND: Recent advancements in deep learning have significantly impacted ophthalmology, especially in glaucoma, a leading cause of irreversible blindness worldwide. In this study, we developed a reliable predictive model for glaucoma detection using deep learning models based on clinical data, social and behavior risk factor, and demographic data from 1652 participants, split evenly between 826 control subjects and 826 glaucoma patients. METHODS: We extracted structural data from control and glaucoma patients' electronic health records (EHR). Three distinct machine learning classifiers, the Random Forest and Gradient Boosting algorithms, as well as the Sequential model from the Keras library of TensorFlow, were employed to conduct predictive analyses across our dataset. Key performance metrics such as accuracy, F1 score, precision, recall, and the area under the receiver operating characteristics curve (AUC) were computed to both train and optimize these models. RESULTS: The Random Forest model achieved an accuracy of 67.5%, with a ROC AUC of 0.67, outperforming the Gradient Boosting and Sequential models, which registered accuracies of 66.3% and 64.5%, respectively. Our results highlighted key predictive factors such as intraocular pressure, family history, and body mass index, substantiating their roles in glaucoma risk assessment. CONCLUSIONS: This study demonstrates the potential of utilizing readily available clinical, lifestyle, and demographic data from EHRs for glaucoma detection through deep learning models. While our model, using EHR data alone, has a lower accuracy compared to those incorporating imaging data, it still offers a promising avenue for early glaucoma risk assessment in primary care settings. The observed disparities in model performance and feature significance show the importance of tailoring detection strategies to individual patient characteristics, potentially leading to more effective and personalized glaucoma screening and intervention.

Comparative analysis of traction forces in normal and glaucomatous trabecular meshwork cells within a 3D, active fluid-structure interaction culture environment.

This study presents a 3D in vitro cell culture model, meticulously 3D printed to replicate the conventional aqueous outflow pathway anatomical structure, facilitating the study of trabecular meshwork (TM) cellular responses under glaucomatous conditions. Glaucoma affects TM cell functionality, leading to extracellular matrix (ECM) stiffening, enhanced cell-ECM adhesion, and obstructed aqueous humor outflow. Our model, reconstructed from polyacrylamide gel with elastic moduli of 1.5 and 21.7 kPa, is based on serial block-face scanning electron microscopy images of the outflow pathway. It allows for quantifying 3D, depth-dependent, dynamic traction forces exerted by both normal and glaucomatous TM cells within an active fluid-structure interaction (FSI) environment. In our experimental design, we designed two scenarios: a control group with TM cells observed over 20 hours without flow (static setting), focusing on intrinsic cellular contractile forces, and a second scenario incorporating active FSI to evaluate its impact on traction forces (dynamic setting). Our observations revealed that active FSI results in higher traction forces (normal: 1.83-fold and glaucoma: 2.24-fold) and shear strains (normal: 1.81-fold and glaucoma: 2.41-fold), with stiffer substrates amplifying this effect. Glaucomatous cells consistently exhibited larger forces than normal cells. Increasing gel stiffness led to enhanced stress fiber formation in TM cells, particularly in glaucomatous cells. Exposure to active FSI dramatically altered actin organization in both normal and glaucomatous TM cells, particularly affecting cortical actin stress fiber arrangement. This model while preliminary offers a new method in understanding TM cell biomechanics and ECM stiffening in glaucoma, highlighting the importance of FSI in these processes. STATEMENT OF SIGNIFICANCE: This pioneering project presents an advanced 3D in vitro model, meticulously replicating the human trabecular meshwork's anatomy for glaucoma research. It enables precise quantification of cellular forces in a dynamic fluid-structure interaction, a leap forward from existing 2D models. This advancement promises significant insights into trabecular meshwork cell biomechanics and the stiffening of the extracellular matrix in glaucoma, offering potential pathways for innovative treatments. This research is positioned at the forefront of ocular disease study, with implications that extend to broader biomedical applications.

Segmental biomechanics of the normal and glaucomatous human aqueous outflow pathway.

The conventional aqueous outflow pathway, encompassing the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and inner wall endothelium of Schlemm's canal (SC), governs intraocular pressure (IOP) regulation. This study targets the biomechanics of low-flow (LF) and high-flow (HF) regions within the aqueous humor outflow pathway in normal and glaucomatous human donor eyes, using a combined experimental and computational approach. LF and HF TM/JCT/SC complex tissues from normal and glaucomatous eyes underwent uniaxial tensile testing. Dynamic motion of the TM/JCT/SC complex was recorded using customized green-light optical coherence tomography during SC pressurization in cannulated anterior segment wedges. A hyperviscoelastic model quantified TM/JCT/SC complex properties. A fluid-structure interaction model simulated tissue-aqueous humor interaction. FluoSpheres were introduced into the pathway via negative pressure in the SC, with their motion tracked using two-photon excitation microscopy. Tensile test results revealed that the elastic moduli of the LF and HF regions in glaucomatous eyes are 3.5- and 1.5-fold stiffer than the normal eyes, respectively. The FE results also showed significantly larger shear moduli in the TM, JCT, and SC of the glaucomatous eyes compared to the normal subjects. The LF regions in normal eyes demonstrated larger elastic moduli compared to the HF regions in glaucomatous eyes. The resultant strain in the outflow tissues and velocity of the aqueous humor in the FSI models were in good agreement with the digital volume correlation and 3D particle image velocimetry data, respectively. This study uncovers stiffer biomechanical responses in glaucomatous eyes, with LF regions stiffer than HF regions in both normal and glaucomatous eyes. STATEMENT OF SIGNIFICANCE: This study delves into the biomechanics of the conventional aqueous outflow pathway, a crucial regulator of intraocular pressure and ocular health. By analyzing mechanical differences in low-flow and high-flow regions of normal and glaucomatous eyes, this research unveils the stiffer response in glaucomatous eyes. The distinction between regions' properties offers insights into aqueous humor outflow regulation, while the integration of experimental and computational methods enhances credibility. These findings have potential implications for disease management and present a vital step toward innovative ophthalmic interventions. This study advances our understanding of glaucoma's biomechanical basis and its broader impact on ocular health.

Implementing new computational methods for the study of JCT and SC inner wall basement membrane biomechanics and hydrodynamics.

PURPOSE: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and the inner wall endothelium of Schlemm's canal (SC), regulates intraocular pressure (IOP) by controlling the aqueous humor outflow resistance. Despite its importance, our understanding of the biomechanics and hydrodynamics within this region remains limited. Fluid-structure interaction (FSI) offers a way to estimate the biomechanical properties of the JCT and SC under various loading and boundary conditions, providing valuable insights that are beyond the reach of current imaging techniques. METHODS: In this study, a normal human eye was fixed at a pressure of 7 mm Hg, and two radial wedges of the TM tissues, which included the SC inner wall basement membrane and JCT, were dissected, processed, and imaged using 3D serial block-face scanning electron microscopy (SBF-SEM). Four different sets of images were used to create 3D finite element (FE) models of the JCT and inner wall endothelial cells of SC with their basement membrane. The outer JCT portion was carefully removed as the outflow resistance is not in that region, leaving only the SCE inner wall and a few µm of the tissue, which does contain the resistance. An inverse iterative FE algorithm was then utilized to calculate the unloaded geometry of the JCT/SC complex at an aqueous humor pressure of 0 mm Hg. Then in the model, the intertrabecular spaces, pores, and giant vacuole contents were replaced by aqueous humor, and FSI was employed to pressurize the JCT/SC complex from 0 to 15 mm Hg. RESULTS: In the JCT/SC complex, the shear stress of the aqueous humor is not evenly distributed. Areas proximal to the inner wall of SC experience larger stresses, reaching up to 10 Pa, while those closer to the JCT undergo lower stresses, approximately 4 Pa. Within this complex, giant vacuoles with or without I-pore behave differently. Those without I-pores experience a more significant strain, around 14%, compared to those with I-pores, where the strain is roughly 9%. CONCLUSIONS: The distribution of aqueous humor wall shear stress is not uniform within the JCT/SC complex, which may contribute to our understanding of the underlying selective mechanisms in the pathway.

Dynamic traction force in trabecular meshwork cells: A 2D culture model for normal and glaucomatous states.

Glaucoma, which is associated with intraocular pressure (IOP) elevation, results in trabecular meshwork (TM) cellular dysfunction, leading to increased rigidity of the extracellular matrix (ECM), larger adhesion forces between the TM cells and ECM, and higher resistance to aqueous humor drainage. TM cells sense the mechanical forces due to IOP dynamic and apply multidimensional forces on the ECM. Recognizing the importance of cellular forces in modulating various cellular activities and development, this study is aimed to develop a 2D in vitro cell culture model to calculate the 3D, depth-dependent, dynamic traction forces, tensile/compressive/shear strain of the normal and glaucomatous human TM cells within a deformable polyacrylamide (PAM) gel substrate. Normal and glaucomatous human TM cells were isolated, cultured, and seeded on top of the PAM gel substrate with embedded FluoSpheres, spanning elastic moduli of 1.5 to 80 kPa. Sixteen-hour post-seeding live confocal microscopy in an incubator was conducted to Z-stack image the 3D displacement map of the FluoSpheres within the PAM gels. Combined with the known PAM gel stiffness, we ascertained the 3D traction forces in the gel. Our results revealed meaningfully larger traction forces in the glaucomatous TM cells compared to the normal TM cells, reaching depths greater than 10-µm in the PAM gel substrate. Stress fibers in TM cells increased with gel rigidity, but diminished when stiffness rose from 20 to 80 kPa. The developed 2D cell culture model aids in understanding how altered mechanical properties in glaucoma impact TM cell behavior and aqueous humor outflow resistance. STATEMENT OF SIGNIFICANCE: Glaucoma, a leading cause of irreversible blindness, is intricately linked to elevated intraocular pressures and their subsequent cellular effects. The trabecular meshwork plays a pivotal role in this mechanism, particularly its interaction with the extracellular matrix. This research unveils an advanced 2D in vitro cell culture model that intricately maps the complex 3D forces exerted by trabecular meshwork cells on the extracellular matrix, offering unparalleled insights into the cellular biomechanics at play in both healthy and glaucomatous eyes. By discerning the changes in these forces across varying substrate stiffness levels, we bridge the gap in understanding between cellular mechanobiology and the onset of glaucoma. The findings stand as a beacon for potential therapeutic avenues, emphasizing the gravity of cellular/extracellular matrix interactions in glaucoma's pathogenesis and setting the stage for targeted interventions in its early stages.

Biomechanics of the JCT and SC Inner Wall Endothelial Cells with Their Basement Membrane Using 3D Serial Block-Face Scanning Electron Microscopy.

BACKGROUND: More than ~70% of the aqueous humor exits the eye through the conventional aqueous outflow pathway that is comprised of the trabecular meshwork (TM), juxtacanalicular tissue (JCT), the inner wall endothelium of Schlemm's canal (SC). The flow resistance in the JCT and SC inner wall basement membrane is thought to play an important role in the regulation of the intraocular pressure (IOP) in the eye, but current imaging techniques do not provide enough information about the mechanics of these tissues or the aqueous humor in this area. METHODS: A normal human eye was perfusion-fixed and a radial wedge of the TM tissue from a high-flow region was dissected. The tissues were then sliced and imaged using serial block-face scanning electron microscopy. Slices from these images were selected and segmented to create a 3D finite element model of the JCT and SC cells with an inner wall basement membrane. The aqueous humor was used to replace the intertrabecular spaces, pores, and giant vacuoles, and fluid-structure interaction was employed to couple the motion of the tissues with the aqueous humor. RESULTS: Higher tensile stresses (0.8-kPa) and strains (25%) were observed in the basement membrane beneath giant vacuoles with open pores. The volumetric average wall shear stress was higher in SC than in JCT/SC. As the aqueous humor approached the inner wall basement membrane of SC, the velocity of the flow decreased, resulting in the formation of small eddies immediately after the flow left the inner wall. CONCLUSIONS: Improved modeling of SC and JCT can enhance our understanding of outflow resistance and funneling. Serial block-face scanning electron microscopy with fluid-structure interaction can achieve this, and the observed micro-segmental flow patterns in ex vivo perfused human eyes suggest a hypothetical mechanism.

Digital exploration of selected heavy metals using Random Forest and a set of environmental covariates at the watershed scale.

The current study was established for predicting some selected heavy metals (HMs) including Zn, Mn, Fe, Co, Cr, Ni, and Cu, by applying random forest (RF) and a set of environmental covariates at watershed scale. The objectives were to find out the most effective combination of variables and controlling factors on the variability of HMs in a semiarid watershed in central Iran. One hundred locations were selected in the given watershed in the hypercube manner and soil samples from a surface 0-20 cm depth and concentration of HMs and some soil properties were measured in the laboratory. Three scenarios of input variables were defined for HMs prediction. The results revealed that the first scenario (remote sensing + topographic attributes) explained about 27-34% of the variability in HMs. Inclusion of a thematic map to the scenario I, improved the prediction accuracy for all HMs. Scenario III (remote sensing data+ topographic attributes + soil properties) was the most efficient scenario for prediction of HMs with R2 values ranging from 0.32 for Cu to 0.42 for Fe. Similarly, the lowest nRMSE was found for all HMs in scenario III, ranging from 0.271 for Fe to 0.351 for Cu. Among the soil properties, clay content and magnetic susceptibility were the most important variables, and also some remote sensing data (Carbonate index, Soil adjusted vegetation index, Band2, and Band7) and topographic attributes (mainly control soil redistribution along the landscape) were the most efficient variables for estimating HMs. We concluded that the RF model with a combination of remote sensing data, topographic attributes, and assisting of thematic maps such as land use in the studied watershed could reliably predict HMs content.

Morphological and biomechanical analyses of the human healthy and glaucomatous aqueous outflow pathway: Imaging-to-modeling.

BACKGROUND AND OBJECTIVE: Intraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway. Primary open angle glaucoma (POAG) is often associated with IOP elevation that occurs due to an abnormally high outflow resistance across the outflow pathway. Outflow tissues are viscoelastic and actively interact with aqueous humor dynamics through a two-way fluid-structure interaction coupling. While glaucoma affects the morphology and stiffness of the outflow tissues, their biomechanics and hydrodynamics in glaucoma eyes remain largely unknown. This research aims to develop an image-to-model method allowing the biomechanics and hydrodynamics of the conventional aqueous outflow pathway to be studied. METHODS: We used a combination of X-ray computed tomography and scanning electron microscopy to reconstruct high-fidelity, eye-specific, 3D microstructural finite element models of the healthy and glaucoma outflow tissues in cellularized and decellularized conditions. The viscoelastic TM/JCT/SC complex finite element models with embedded viscoelastic beam elements were subjected to a physiological IOP load boundary; the stresses/strains and the flow state were calculated using fluid-structure interaction and computational fluid dynamics. RESULTS: Based on the resultant hydrodynamics parameters across the outflow pathway, the primary site of outflow resistance in healthy eyes was in the JCT and immediate vicinity of the SC inner wall, while the majority of the outflow resistance in the glaucoma eyes occurred in the TM. The TM and JCT in the glaucoma eyes showed 1.32-fold and 1.13-fold larger beam thickness and smaller trabecular space size (2.24-fold and 1.50-fold) compared to the healthy eyes. CONCLUSIONS: Characterizing the accurate morphology of the outflow tissues may significantly contribute to constructing more accurate, robust, and reliable models, that can eventually help to better understand the dynamic IOP regulation, hydrodynamics of the aqueous humor, and outflow resistance dynamic in the human eyes. This model demonstrates proof of concept for determining changes to outflow resistance in healthy and glaucomatous tissues and thus may be utilized in larger cohorts of donor tissues where disease specificity, race, age, and gender of the eye donors may be accounted for.

Developing an experimental-computational workflow to study the biomechanics of the human conventional aqueous outflow pathway.

The aqueous humor actively interacts with the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm's canal (SC) through a dynamic fluid-structure interaction (FSI) coupling. Despite the fact that intraocular pressure (IOP) undergoes significant fluctuations, our understanding of the hyperviscoelastic biomechanical properties of the aqueous outflow tissues is limited. In this study, a quadrant of the anterior segment from a normal human donor eye was dynamically pressurized in the SC lumen, and imaged using a customized optical coherence tomography (OCT). The TM/JCT/SC complex finite element (FE) with embedded collagen fibrils was reconstructed based on the segmented boundary nodes in the OCT images. The hyperviscoelastic mechanical properties of the outflow tissues' extracellular matrix with embedded viscoelastic collagen fibrils were calculated using an inverse FE-optimization method. Thereafter, the 3D microstructural FE model of the TM, with adjacent JCT and SC inner wall, from the same donor eye was constructed using optical coherence microscopy and subjected to a flow load-boundary from the SC lumen. The resultant deformation/strain in the outflow tissues was calculated using the FSI method, and compared to the digital volume correlation (DVC) data. TM showed larger shear modulus (0.92 MPa) compared to the JCT (0.47 MPa) and SC inner wall (0.85 MPa). Shear modulus (viscoelastic) was larger in the SC inner wall (97.65 MPa) compared to the TM (84.38 MPa) and JCT (56.30 MPa). The conventional aqueous outflow pathway is subjected to a rate-dependent IOP load-boundary with large fluctuations. This necessitates addressing the biomechanics of the outflow tissues using hyperviscoelastic material-model. STATEMENT OF SIGNIFICANCE: While the human conventional aqueous outflow pathway is subjected to a large-deformation and time-dependent IOP load-boundary, we are not aware of any studies that have calculated the hyperviscoelastic mechanical properties of the outflow tissues with embedded viscoelastic collagen fibrils. A quadrant of the anterior segment of a normal humor donor eye was dynamically pressurized from the SC lumen with relatively large fluctuations. The TM/JCT/SC complex were OCT imaged and the mechanical properties of the tissues with embedded collagen fibrils were calculated using the inverse FE-optimization algorithm. The resultant displacement/strain in the FSI outflow model was validated versus the DVC data. The proposed experimental-computational workflow may significantly contribute to understanding of the effects of different drugs on the biomechanics of the conventional aqueous outflow pathway.

A position- and time-dependent pressure profile to model viscoelastic mechanical behavior of the brain tissue due to tumor growth.

This study proposed a computational framework to calculate the resultant position- and time-dependent pressure profile on the brain tissue due to tumor growth. A finite element (FE) patch of the brain tissue was constructed and an inverse dynamic FE-optimization algorithm was used to calculate its viscoelastic mechanical properties under compressive uniaxial loading. Two patient-specific post-tumor resection FE models were input to the FE-optimization algorithm to calculate the optimized 3rd-order position-dependent and normal distribution time-dependent pressure profile parameters. The optimized viscoelastic material properties, the most suitable simulation time, and the optimized 3rd-order position- and -time-dependent pressure profiles were calculated.

The interactions of Cr (VI) concentrations and amendments (biochar and manure) on growth and metal accumulation of two species of Salicornia in contaminated soil.

Heavy metals are among the most dangerous contaminants in the environment. Organic components and plant species that can accumulate and stabilize heavy metals in their organs are a good option for soil remediation of these elements. Therefore, this study aimed to investigate the effects of manure and biochar on the accumulation of heavy metals by Salicornia species. Salicornia persica Akhani and Salicornia perspolitana Akhani were cultivated outdoor in experimental pots. The effects of experimental treatments, including Cr (VI) concentrations, manure, and biochar on the two studied species, were investigated. The results indicated a significant effect (p < 0.05) of biochar on the accumulation of heavy metals by two species, S. persica and S. perspolitana, so that Cr concentrations in the roots and shoots were 258 and 5.41 mg/kg, respectively. In addition, Cr accumulations under manure treatments in the roots and shoots were 334.34 and 9.79 mg/kg, respectively. The content of photosynthetic pigments in both S. persica and S. perspolitana species under biochar treatment was higher than in control and manure treatments. In general, one can conclude that the accumulation of Cr in S. perspolitana was higher than in S. persica. Applying biochar and manure amendments could stabilize Cr in soil and reduce Cr accumulation in both S. persica and S. perspolitana species.

Modeling the Endothelial Glycocalyx Layer in the Human Conventional Aqueous Outflow Pathway.

A layer of proteoglycans and glycoproteins known as glycocalyx covers the surface of the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm's canal (SC) inner wall of the conventional aqueous outflow pathway in the eye. This has been shown to play a role in the mechanotransduction of fluid shear stress and in the regulation of the outflow resistance. The outflow resistance in the conventional outflow pathway is the main determinant of the intraocular pressure (IOP) through an active, two-way, fluid-structure interaction coupling between the outflow tissues and aqueous humor. A 3D microstructural finite element (FE) model of a healthy human eye TM/JCT/SC complex with interspersed aqueous humor was constructed. A very thin charged double layer that represents the endothelial glycocalyx layer covered the surface of the elastic outflow tissues. The aqueous humor was modeled as electroosmotic flow that is charged when it is in contact with the outflow tissues. The electrical-fluid-structure interaction (EFSI) method was used to couple the charged double layer (glycocalyx), fluid (aqueous humor), and solid (outflow tissues). When the IOP was elevated to 15 mmHg, the maximum aqueous humor velocity in the EFSI model was decreased by 2.35 mm/s (9%) compared to the fluid-structure interaction (FSI) model. The charge or electricity in the living human conventional outflow pathway generated by the charged endothelial glycocalyx layer plays a minor biomechanical role in the resultant stresses and strains as well as the hydrodynamics of the aqueous humor.

The Effect of Intraocular Pressure Load Boundary on the Biomechanics of the Human Conventional Aqueous Outflow Pathway.

BACKGROUND: Aqueous humor outflow resistance in the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway actively contribute to intraocular pressure (IOP) regulation. Outflow resistance is actively affected by the dynamic outflow pressure gradient across the TM, JCT, and SC inner wall tissues. The resistance effect implies the presence of a fluid-structure interaction (FSI) coupling between the outflow tissues and the aqueous humor. However, the biomechanical interactions between viscoelastic outflow tissues and aqueous humor dynamics are largely unknown. METHODS: A 3D microstructural finite element (FE) model of a healthy human eye TM/JCT/SC complex was constructed with elastic and viscoelastic material properties for the bulk extracellular matrix and embedded elastic cable elements. The FE models were subjected to both idealized and a physiologic IOP load boundary using the FSI method. RESULTS: The elastic material model for both the idealized and physiologic IOP load boundary at equal IOPs showed similar stresses and strains in the outflow tissues as well as pressure in the aqueous humor. However, outflow tissues with viscoelastic material properties were sensitive to the IOP load rate, resulting in different mechanical and hydrodynamic responses in the tissues and aqueous humor. CONCLUSIONS: Transient IOP fluctuations may cause a relatively large IOP difference of ~20 mmHg in a very short time frame of ~0.1 s, resulting in a rate stiffening in the outflow tissues. Rate stiffening reduces strains and causes a rate-dependent pressure gradient across the outflow tissues. Thus, the results suggest it is necessary to use a viscoelastic material model in outflow tissues that includes the important role of IOP load rate.

Clinical Validation of a Smartphone-based Handheld ECG Device: A Validation Study.

BACKGROUND: Remote cardiac monitoring and screening have already become an integral telemedicine component. The wide usage of several different wireless electrocardiography (ECG) devices warrants a validation study on their accuracy and reliability. METHODS: Totally, 300 inpatients with the Nabz Hooshmand-1 handheld ECG device and the GE MAC 1200 ECG system (as the reference) were studied to check the accuracy of the devices in 1 and 6-limb lead performance. Simultaneous 10-second resting ECGs were assessed for the most common ECG parameters in lead I. Afterward, 6-lead ECGs (limb leads), were performed immediately and studied for their morphologies. RESULTS: Of the 300 patients, 297 had acceptable ECG quality in both devices for simultaneous lead I ECGs. The ECGs were inspected on-screen by a cardiologist for their rhythms, rates, axes, numbers, morphologies of premature atrial and ventricular beats, morphologies and amplitudes of PQRST waves, P-wave durations, QRS-wave durations, P-R intervals, and QT intervals. No significant differences were detected between the devices, and no major abnormalities were missed. Six-limb lead ECGs were obtained in 284 patients, of whom 281 had acceptable quality in ECGs by both devices. The morphology matching evaluation of the ECGs demonstrated an overall 98% compatibility rate, with the highest compatibility in lead I and the lowest in lead augmented vector foot. CONCLUSIONS: The diagnosis of critical pathological rhythms, including atrial fibrillation and high-grade atrioventricular node block, was not missed by the Nabz Hooshmand-1 and GE MAC 1200 ECG devices. Accordingly, rhythm detection as the primary purpose of handheld ECG devices was highly accurate. Both devices had acceptable sensitivity to diagnose long P-R and long and short QT intervals. Although the modern technology of smartphones and the physical inability for the 6-limb mode might cause old patients difficulty in utilizing such devices, their use for screening and follow-up is safe.

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues.

Purpose: The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor. Methods: Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine. Results: Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position (P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC (P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg (P < 0.05). Conclusions: Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

Viscoelastic Biomechanical Properties of the Conventional Aqueous Outflow Pathway Tissues in Healthy and Glaucoma Human Eyes.

BACKGROUND: Although the tissues comprising the ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, the viscoelastic mechanical properties of the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) inner wall are largely unknown. METHODS: A quadrant of the anterior segment from two human donor eyes at low- and high-flow (LF and HF) outflow regions was pressurized and imaged using optical coherence tomography (OCT). A finite element (FE) model of the TM, the adjacent JCT, and the SC inner wall was constructed and viscoelastic beam elements were distributed in the extracellular matrix (ECM) of the TM and JCT to represent anisotropic collagen. An inverse FE-optimization algorithm was used to calculate the viscoelastic properties of the ECM/beam elements such that the TM/JCT/SC model and OCT imaging data best matched over time. RESULTS: The ECM of the glaucoma tissues showed significantly larger time-dependent shear moduli compared to the heathy tissues. Significantly larger shear moduli were also observed in the LF regions of both the healthy and glaucoma eyes compared to the HF regions. CONCLUSIONS: The outflow tissues in both glaucoma eyes and HF regions are stiffer and less able to respond to dynamic IOP.

Interaction of the Blood Components with Ascending Thoracic Aortic Aneurysm Wall: Biomechanical and Fluid Analyses.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is an asymptomatic localized dilation of the aorta that is prone to rupture with a high rate of mortality. While diameter is the main risk factor for rupture assessment, it has been shown that the peak wall stress from finite element (FE) simulations may contribute to refinement of clinical decisions. In FE simulations, the intraluminal boundary condition is a single-phase blood flow that interacts with the thoracic aorta (TA). However, the blood is consisted of red blood cells (RBCs), white blood cells (WBCs), and plasma that interacts with the TA wall, so it may affect the resultant stresses and strains in the TA, as well as hemodynamics of the blood. METHODS: In this study, discrete elements were distributed in the TA lumen to represent the blood components and mechanically coupled using fluid-structure interaction (FSI). Healthy and aneurysmal human TA tissues were subjected to axial and circumferential tensile loadings, and the hyperelastic mechanical properties were assigned to the TA and ATAA FE models. RESULTS: The ATAA showed larger tensile and shear stresses but smaller fluid velocity compared to the ATA. The blood components experienced smaller shear stress in interaction with the ATAA wall compared to TA. The computational fluid dynamics showed smaller blood velocity and wall shear stress compared to the FSI. CONCLUSIONS: This study is a first proof of concept, and future investigations will aim at validating the novel methodology to derive a more reliable ATAA rupture risk assessment considering the interaction of the blood components with the TA wall.

Modeling the biomechanics of the conventional aqueous outflow pathway microstructure in the human eye.

BACKGROUND AND OBJECTIVE: Intraocular pressure (IOP) is determined by aqueous humor outflow resistance, which is a function of the combined resistance of Schlemm's canal (SC) endothelium and the trabecular meshwork (TM) and their interactions in the juxtacanalicular connective tissue (JCT) region. Aqueous outflow in the conventional outflow pathway results in pressure gradient across the TM, JCT, and SC inner wall, and induces mechanical stresses and strains that influence the geometry and homeostasis of the outflow system. The outflow resistance is affected by alteration in tissues' geometry, so there is potential for active, two-way, fluid-structure interaction (FSI) coupling between the aqueous humor (fluid) and the TM, JCT, and SC inner wall (structure). However, our understanding of the biomechanical interactions of the aqueous humor with the outflow connective tissues and its contribution to the outflow resistance regulation is incomplete. METHODS: In this study, a microstructural finite element (FE) model of a human eye TM, JCT, and SC inner wall was constructed from a segmented, high-resolution histologic 3D reconstruction of the human outflow system. Three different elastic moduli (0.004, 0.128, and 51.5 MPa based on prior reports) were assigned to the TM/JCT complex while the elastic modulus of the SC inner wall was kept constant at 0.00748 MPa. The hydraulic conductivity was programmed separately for the TM, JCT, and SC inner wall using a custom subroutine. Cable elements were embedded into the TM and JCT extracellular matrix to represent the directional stiffness imparted by anisotropic collagen fibril orientation. The resultant stresses and strains in the outflow system were calculated using fluid-structure interaction method. RESULTS: The higher TM/JCT stiffness resulted in larger stresses, but smaller strains in the outflow connective tissues, and resulted in a 4- and 5-fold larger pressure drop across the SC inner wall, respectively, compared to the most compliant model. Funneling through µm-sized SC endothelial pores was evident in the models at lower tissue stiffness, but aqueous flow was more turbulent in models with higher TM/JCT stiffness. CONCLUSIONS: The mechanical properties of the outflow tissues play a crucial role in the hydrodynamics of the aqueous humor in the conventional outflow system.