A Comprehensive Look at In Vitro Angiogenesis Image Analysis Software.

One of the complex challenges faced presently by tissue engineering (TE) is the development of vascularized constructs that accurately mimic the extracellular matrix (ECM) of native tissue in which they are inserted to promote vessel growth and, consequently, wound healing and tissue regeneration. TE technique is characterized by several stages, starting from the choice of cell culture and the more appropriate scaffold material that can adequately support and supply them with the necessary biological cues for microvessel development. The next step is to analyze the attained microvasculature, which is reliant on the available labeling and microscopy techniques to visualize the network, as well as metrics employed to characterize it. These are usually attained with the use of software, which has been cited in several works, although no clear standard procedure has been observed to promote the reproduction of the cell response analysis. The present review analyzes not only the various steps previously described in terms of the current standards for evaluation, but also surveys some of the available metrics and software used to quantify networks, along with the detection of analysis limitations and future improvements that could lead to considerable progress for angiogenesis evaluation and application in TE research.

Multiscale Homogenization Techniques for TPMS Foam Material for Biomedical Structural Applications.

Multiscale techniques, namely homogenization, result in significant computational time savings in the analysis of complex structures such as lattice structures, as in many cases it is inefficient to model a periodic structure in full detail in its entire domain. The elastic and plastic properties of two TPMS-based cellular structures, the gyroid, and the primitive surface are studied in this work through numerical homogenization. The study enabled the development of material laws for the homogenized Young's modulus and homogenized yield stress, which correlated well with experimental data from the literature. It is possible to use the developed material laws to run optimization analyses and develop optimized functionally graded structures for structural applications or reduced stress shielding in bio-applications. Thus, this work presents a study case of a functionally graded optimized femoral stem where it was shown that the porous femoral stem built with Ti-6Al-4V can minimize stress shielding while maintaining the necessary load-bearing capacity. It was shown that the stiffness of cementless femoral stem implant with a graded gyroid foam presents stiffness that is comparable to that of trabecular bone. Moreover, the maximum stress in the implant is lower than the maximum stress in trabecular bone.

Bladder Wall Stiffness after Cystectomy in Bladder Cancer Patients: A Preliminary Study.

Bladder cancer (BlCa), specifically urothelial carcinomas, is a heterogeneous disease that derives from the urothelial lining. Two main classes of BlCa are acknowledged: the non-muscle invasive BlCa and the muscle-invasive BlCa; the latter constituting an aggressive disease which invades locally and metastasizes systemically. Distinguishing the specific microenvironment that cancer cells experience between mucosa and muscularis propria layers can help elucidate how these cells acquire invasive capacities. In this work, we propose to measure the micromechanical properties of both mucosa and muscularis propria layers of the bladder wall of BlCa patients, using atomic force microscopy (AFM). To do that, two cross-sections of both the macroscopically normal urinary bladder wall and the bladder wall adjacent to the tumor were collected and immediately frozen, prior to AFM samples analysis. The respective "twin" formalin-fixed paraffin-embedded tissue fragments were processed and later evaluated for histopathological examination. H&E staining suggested that tumors promoted the development of muscle-like structures in the mucosa surrounding the neoplastic region. The average Young's modulus (cell stiffness) in tumor-adjacent specimens was significantly higher in the muscularis propria than in the mucosa. Similarly, the tumor-free specimens had significantly higher Young's moduli in the muscularis propria than in the urothelium. Young's moduli were higher in all layers of tumor-adjacent tissues when compared with tumor-free samples. Here we provide insights into the stiffness of the bladder wall layers, and we show that the presence of tumor in the surrounding mucosa leads to an alteration of its smooth muscle content. The quantitative assessment of stiffness range here presented provides essential data for future research on BlCa and for understanding how the biomechanical stimuli can modulate cancer cells' capacity to invade through the different bladder layers.

Artificial intelligence and capsule endoscopy: automatic detection of vascular lesions using a convolutional neural network.

BACKGROUND: Capsule endoscopy (CE) is the first line for evaluation of patients with obscure gastrointestinal bleeding. A wide range of small intestinal vascular lesions with different hemorrhagic potential are frequently found in these patients. Nevertheless, reading CE exams is time-consuming and prone to errors. Convolutional neural networks (CNN) are artificial intelligence tools with high performance levels in image analysis. This study aimed to develop a CNN-based model for identification and differentiation of vascular lesions with distinct hemorrhagic potential in CE images. METHODS: The development of the CNN was based on a database of CE images. This database included images of normal small intestinal mucosa, red spots, and angiectasia/varices. The hemorrhagic risk was assessed by Saurin's classification. For CNN development, 11,588 images (9525 normal mucosa, 1026 red spots, and 1037 angiectasia/varices) were ultimately extracted. Two image datasets were created for CNN training and testing. RESULTS: The network was 91.8% sensitive and 95.9% specific for detection of vascular lesions, providing accurate predictions in 94.4% of cases. In particular, the CNN had a sensitivity and specificity of 97.1% and 95.3%, respectively, for detection of red spots. Detection of angiectasia/varices occurred with a sensitivity of 94.1% and a specificity of 95.1%. The CNN had a frame reading rate of 145 frames/sec. CONCLUSIONS: The developed algorithm is the first CNN-based model to accurately detect and distinguish enteric vascular lesions with different hemorrhagic risk. CNN-assisted CE reading may improve the diagnosis of these lesions and overall CE efficiency.

Influence of the basilar membrane shape and mechanical properties in the cochlear response: A numerical study.

Hearing impairment is one of the most common health disorders, affecting individuals of all ages, reducing considerably their quality of life. At present, it is known that during an acoustic stimulation a travelling wave is developed inside the cochlea. Existing mathematical and numerical models available in the literature try to describe the shape of this travelling wave, the majority of them present a set of approaches based on some limitations either or both of the mechanical properties used and the geometrical description of the realistic representation. The present numerical study highlights the distinctions of using a spiral model of the cochlea, by comparing the obtained results with a straight, or simplified model. The influence of the implantation of transversely isotropic mechanical models was also studied, by comparing the basilar membrane with isotropic and transversely isotropic mechanical properties. Values of the root mean square error calculated for all models show a greater proximity of the cochlear mapping to the Greenwood function when the basilar membrane is assumed with transversely isotropic mechanical properties for both straight and spiral model. The root-mean square errors calculated were: 2.05, 1.70, 2.72, 2.08 mm, for the straight-isotropic, straight-transversely isotropic, spiral-isotropic and spiral-transversely isotropic model, respectively.

Association Between Physical Activity Level and Pelvic Floor Muscle Variables in Women.

In order to investigate the potential impact of physical activity (PA) on pelvic floor muscle (PFM) function, a cross-sectional study was made to analyse the association between PA level and vaginal resting pressure (VRP) and PFM strength and endurance. Thirty-eight continent women and 20 women with stress urinary incontinence (SUI) aged 19 to 49 years were enrolled in the study. PFM variables were assessed by manometry. The PA level was assessed through the International Physical Activity Questionnaire - Short Form. The International Consultation on Incontinence Questionnaire-Urinary Incontinence - Short Form was applied to identify SUI. Pearson's correlation coefficients were applied to estimate the association between PA and PFM variables. Incontinent women were classified as having a high PA level compared to the continent ones (65.0% vs 34.2%, respectively; p=0.030). There was a positive weak association between PA and VRP in continent (r=0.377) and an inverse association in incontinent women (r=-0.458). No associations were found between PA and PFM strength and endurance. Further studies are needed in order to identify a causal association between PA and SUI.

Modelling skin wound healing angiogenesis: A review.

The occurrence of wounds is a main health concern in Western society due to their high frequency and treatment cost. During wound healing, the formation of a functional blood vessel network through angiogenesis is an essential process. Angiogenesis allows the reestablishment of the normal blood flow, the sufficient exchange of oxygen and nutrients and the removal of metabolic waste, necessary for cell proliferation and viability. Mathematical and computational models provide new tools to improve the healing process. In fact, over the last thirty years, in silico models have been continuously formulated to describe the effect of several biological and mechanical factors in angiogenesis during wound healing. Additionally, with different levels of complexity, these models allow coupling the human skin structure, to distinct cell types and growth factors, to study extracellular matrix composition and to understand its deformation. This paper discusses how in silico models, which are more economical and less time-consuming comparatively to laboratory methodologies, can help test new strategies to promote/optimize angiogenesis. The continuum, cell-based and hybrid mathematical models of wound healing angiogenesis are reviewed in the present paper, in order to identify possible improvements. Accordingly, the development of higher dimension models incorporating multiscale analysis at molecular, cellular and tissue level remains a challenge that future models should consider.

A computational framework to simulate the endolymph flow due to vestibular rehabilitation maneuvers assessed from accelerometer data.

Vertiginous symptoms are one of the most common symptoms in the world, therefore investing in new ways and therapies to avoid the sense of insecurity during the vertigo episodes is of great interest. The classical maneuvers used during vestibular rehabilitation consist in moving the head in specific ways, but it is not fully understood why those steps solve the problem. To better understand this mechanism, a three-dimensional computational model of the semicircular ducts of the inner ear was built using the finite element method, with the simulation of the fluid flow being obtained using particle methods. To simulate the exact movements performed during rehabilitation, data from an accelerometer were used as input for the boundary conditions in the model. It is shown that the developed model responds to the input data as expected, and the results successfully show the fluid flow of the endolymph behaving coherently as a function of accelerometer data. Numerical results at specific time steps are compared with the corresponding head movement, and both particle velocity and position follow the pattern that would be expected, confirming that the model is working as expected. The vestibular model built is an important starting point to simulate the classical maneuvers of the vestibular rehabilitation allowing to understand what happens in the endolymph during the rehabilitation process, which ultimately may be used to improve the maneuvers and the quality of life of patients suffering from vertigo.

Biomechanics of the shoulder girdle: a case study on the effects of union rugby tackles.

PURPOSE: The shoulder girdle is a complex system, comprised by a kinematic chain and stabilizers. Due to the delicate equilibrium and synchronism between mobility and stability, high external loads may compromise its physiology, increasing the risk of injuries. Thus, this study intends to fully characterize the effects of a rugby tackle on the shoulder's anatomy and physiology. METHODS: For the experimental procedures, a matrix of pressure sensors was used, based on the Teckscan® pressure in-soles, force plates, an isokinetic dynamometer and sEMG (surface electromyography). RESULTS: The anterosuperior region of the shoulder girdle confirmed the highest pressure values during impact (100 kPa-200 kPa). Also, the right and left feet performed a vertical peak force of 1286 N (1.4 BW) and 1998 N (2.21 BW), respectively. The muscular activity of the shoulder muscles decreased after performing multiple tackles. CONCLUSIONS: During a tackle, the clavicle, scapula, trapezius and acromioclavicular joint are the anatomical structures with higher risk of injury. Also, the strike force on the feet decreases for stability purposes. After performing multiple impacts the muscular activity of the trapezius and rotator cuff muscles decreases, which may lead, in the long-term, to instability of the shoulder and inefficiency of the scapulohumeral rhythm.

Urinary Incontinence in Physically Active Young Women: Prevalence and Related Factors.

This cross-sectional survey aims to (1) verify the prevalence of urinary incontinence and its impact on the quality of life among nulliparous fit women, and to (2) analyze whether urinary incontinence is influenced by the intensity of the sport (high- vs. low-impact) or by the volume of physical activity (minutes per week) performed. Two hundred forty-five nulliparous women (18-40 years) completed the International Consultation on Incontinence Questionnaire-Short Form, the Kings Health Questionnaire and a questionnaire regarding demographic and training variables. Overall 22.9% of the participants self-reported urinary incontinence, and among them, 60.7% had stress urinary incontinence. Incontinent women demonstrated worse quality of life than continent females (p=0.000). Women practicing high-impact sports presented higher frequency in loss of urine than those practicing low-impact sports (p=0.004). Regardless the intensity of the sport, the volume of exercise showed positive association with the frequency of loss of urine (p=0.005, r=0.475). In conclusion, almost one fourth of the women enrolled in this study reported symptoms of urinary incontinence and worse quality of life than those who were continent. Women who practice high-impact sports or who have higher volume of training should be aware of the symptoms associated with pelvic floor dysfunction, since they seem to predispose to urine leakage.

Effects of the fibers distribution in the human eardrum: A biomechanical study.

The eardrum separates the external ear from the middle ear and it is responsible to convert the acoustical energy into mechanical energy. It is divided by pars tensa and pars flaccida. The aim of this work is to analyze the susceptibility of the four quadrants of the pars tensa under negative pressure, to different lamina propria fibers distribution. The development of associated ear pathology, in particular the formation of retraction pockets, is also evaluated. To analyze these effects, a computational biomechanical model of the tympano-ossicular chain was constructed using computerized tomography images and based on the finite element method. Three fibers distributions in the eardrum middle layer were compared: case 1 (eardrum with a circular band of fibers surrounding all quadrants equally), case 2 (eardrum with a circular band of fibers that decreases in thickness in posterior quadrants), case 3 (eardrum without circular fibers in the posterior/superior quadrant). A static analysis was performed by applying approximately 3000Pa in the eardrum. The pars tensa of the eardrum was divided in four quadrants and the displacement of a central point of each quadrant analyzed. The largest displacements of the eardrum were obtained for the eardrum without circular fibers in the posterior/superior quadrant.

Football practice and urinary incontinence: Relation between morphology, function and biomechanics.

Current evidence points to a high prevalence of urinary incontinence among female athletes. In this context, this study aims to assess if structural and biomechanical characteristics of the pubovisceral muscles may lead to urine leakage. Clinical and demographic data were collected, as well as pelvic Magnetic Resonance Imaging. Furthermore, computational models were built to verify if they were able to reproduce similar biomechanical muscle response as the one measured by dynamic imaging during active contraction by means of the percent error. Compared to the continent ones (n=7), incontinent athletes (n=5) evidenced thicker pubovisceral muscles at the level of the midvagina (p=0.019 and p=0.028 for the right and left sides, respectively). However, there were no differences neither in the strength of contraction in the Oxford Scale or in the displacement of the pelvic floor muscles during simulation of voluntary contraction, which suggests that urine leakage may be related with alterations in the intrafusal fibers than just the result of thicker muscles. Additionally, we found similar values of displacement retrieved from dynamic images and numerical models (6.42 ± 0.36 mm vs. 6.10 ± 0.47 mm; p=0.130), with a percent error ranging from 1.47% to 17.20%. However, further refinements in the mechanical properties of the striated skeletal fibers of the pelvic floor muscles and the inclusion of pelvic organs, fascia and ligaments would reproduce more realistically the pelvic cavity.

Volume of training and the ranking level are associated with the leakage of urine in young female trampolinists.

OBJECTIVES: The aim of this study was to investigate in young nulliparous female trampolinists the hypothetical associations between the level of athletic performance and the volume of training with urine leakage. DESIGN: Cross-sectional cohort study. SETTING: Professional trampolinists. PARTICIPANTS: Twenty-two female athletes participating in a trampoline national championship were included in this study. ASSESSMENT OF RISK FACTORS: The associations for player-related performance variables were evaluated using Spearman rank correlation and Kruskal-Wallis H test verified the differences between the tertiles. MAIN OUTCOME MEASURES: Rate of urinary incontinence (UI) among young athletes and the relationship with the athletic performance. Screening was performed through a questionnaire. This included the demographic sample characterization, the assessment of training volume, and the athletes' ranking in the championship. Additionally, it included the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-UI-SF) to assess the leakage. RESULTS: About 72.7% of the participants reported that they experienced urine leakage during trampoline practice and described that the episodes of leakage started after the beginning of the trampoline. Significant associations between the athletic performance and the training volume were observed with the severity of incontinence. Dividing the sample in tertiles of training volume, it was observed that the third tertile was the one with greatest impact of incontinence on their quality of life (ICIQ score). CONCLUSIONS: The results confirm a high frequency of UI in young trampolinists and reveal a clear identification of the athletes' ranking and the training volume as risk factors to develop and worsen urine loss. CLINICAL RELEVANCE: Special attention from team physicians and trainers is required for this athletes' problem that is often hidden by shame. In addition, female athletes practicing high-impact sports should be informed about the risk to develop pelvic floor muscles dysfunction and should be encouraged to seek help from health professionals to minimize or even eliminate the urine incontinence.

Biomechanical study on the bladder neck and urethral positions: simulation of impairment of the pelvic ligaments.

Excessive mobility of the bladder neck and urethra are common features in stress urinary incontinence. We aimed at assessing, through computational modelling, the bladder neck position taking into account progressive impairment of the pelvic ligaments. Magnetic resonance images of a young healthy female were used to build a computational model of the pelvic cavity. Appropriate material properties and constitutive models were defined. The impairment of the ligaments was simulated by mimicking a reduction in their stiffness. For healthy ligaments, valsalva maneuver led to an increase in the α angle (between the bladder neck-symphysis pubis and the main of the symphysis) from 91.8° (at rest) to 105.7°, and 5.7 mm of bladder neck dislocation, which was similar to dynamic imaging of the same woman (α angle from 80° to 103.3°, and 5mm of bladder neck movement). For 95% impairment, they enlarged to 124.28° and 12 mm. Impairment to the pubourethral ligaments had higher effect than that of vaginal support (115° vs. 108°, and 9.1 vs. 7.3mm). Numerical simulation could predict urethral motion during valsalva maneuver, for both healthy and impaired ligaments. Results were similar to those of continent women and women with stress urinary incontinence published in the literature. Biomechanical analysis of the pubourethral ligaments complements the biomechanical study of the pelvic cavity in urinary incontinence. It may be useful in young women presenting stress urinary incontinence without imaging evidence of urethral and muscle lesions or organ descend during valsalva, and for whom fascial damage are not expected.

The biomechanical effects of stapes replacement by prostheses on the tympano-ossicular chain.

Hearing is a sequence of processes in which the ear translates sound waves into electrical signals, which are then sent to the brain where they are interpreted as sound. The ossicular chain of the middle ear is formed by three ossicles (malleus, incus, and stapes), of which the last and smallest, the stapes, vibrates, thus communicating with the inner ear through the stapes footplate. When abnormal bone formation immobilizes the stapes (otosclerosis), the passage of sound does not correctly occur and hearing can be compromised. In most cases, surgery is an option for its treatment. The stapes is totally or partially replaced by a prosthesis (stapedectomy or stapedotomy, respectively) allowing the passage of sound to the inner ear. This work presents a study on the behavior of different stapes prostheses, considering their biomechanical characteristics. The stapes was replaced by different prostheses, made of dissimilar materials: stainless steel, teflon, and titanium. The umbo and stapes footplate displacements for the models with these prostheses were obtained and compared with the displacements obtained with the model representative of the normal ear. In the models with prostheses, the displacements are found in the hole where the prosthesis is attached.

A level set based algorithm to reconstruct the urinary bladder from multiple views.

The urinary bladder can be visualized from different views by imaging facilities such as computerized tomography and magnetic resonance imaging. Multi-view imaging can present more details of this pelvic organ and contribute to a more reliable reconstruction. Based on the information from multi-view planes, a level set based algorithm is proposed to reconstruct the 3D shape of the bladder using the cross-sectional boundaries. The algorithm provides a flexible solution to handle the discrepancies from different view planes and can obtain an accurate bladder surface with more geometric details.

Determination of expander apparatus displacements and contact pressures on the mucosa using FEM modelling considering mandibular asymmetries.

This paper presents a method for prediction of forces and displacements in the expansion screw of a modified mandibular Schwarz appliance and the contact pressure distributions on the mucosa during malocclusions treatment. A 3D finite element biomechanical model of the complete mandible-mucosa-apparatus set was built using computerised tomographic images of a patient's mandible and constructive solid geometry by computer software. An iterative procedure was developed to handle a boundary condition that takes into account the mandibular asymmetries. The results showed asymmetries in the contact pressure distributions that indicated with precision the patient's malocclusion diagnosis. In vivo measurements of contact pressure using piezoelectric sensors agreed with the computational results. It was shown that the left and right ends of the expansion screw move differently with respect to the patient mandible, even though the expansion screw has an opening mechanism to ensure equal stretching at both ends. The contact pressures between the apparatus and the mucosa vary linearly with applied forces, which can simplify the analysis of the biomechanical behaviour of the expander mandible apparatus. The biomechanical modelling proposed in this paper can be a useful tool to improve malocclusions treatment, safely avoiding the use of forces acting on live structures beyond the biological tolerance, which could result in traumatic effects.