Nonlocal damage evaluation of a sigmoid-based damage model for fibrous biological soft tissues.

The comprehension and modeling of the mechanical behavior of soft biological tissues are essential due to their clinical applications. This knowledge is essential for predicting tissue responses accurately and enhancing our ability to compute the behavior of biological structures and bio-prosthetic devices under specific loading conditions. The current research is centered on modeling the initiation and progression of soft tissues damage, which typically exhibit intricate anisotropic and nonlinear elastic characteristics. For this purpose, the following study presents a comparative analysis of the computational performance of two distinct damage modeling techniques. The first technique employs a well-established damage model, based on a piece-wise exponential damage function as proposed by Calvo et al. (Int J Numer Methods Eng 69:2036-2057, 2007. https://doi.org/10.1002/nme.1825 ). The second approach adopts a sigmoid function, as proposed by López-Campos et al. (Comput Methods Biomech Biomed Eng 23(6):213-223. https://doi.org/10.1080/10255842.2019.1710742 ). The aim of this study is to verify the validity of the López-Campos sigmoid-based damage model to be used in finite element simulation, the implementation of which is unknown. For this proposal, both models were implemented within a commercial Finite Element software package, and their responses to local and non-local damage algorithms were assessed in depth through two standard benchmark tests: a plate with a hole and a ball burst. The results of this study indicate that, for a wide range of cases, such as in-plane stresses, out-plane stresses, stress concentration and contact, all over large displacement conditions, the López-Campos damage model shows a good response to non-local algorithms achieving mesh independence and convergence in all these cases. The results obtained are in line with those obtained for the Calvo's damage model, showing, in addition, larger deformations under in-plane stress and stress concentration conditions and a lower number of iterations under out-plane stress and contact conditions. Consequently, the López-Campos' damage model emerges as a valuable and useful tool in the field of mechanical damage research in biological systems.

Design for Robustness: Bio-Inspired Perspectives in Structural Engineering.

Bio-inspired solutions are widely adopted in different engineering disciplines. However, in structural engineering, these solutions are mainly limited to bio-inspired forms, shapes, and materials. Nature is almost completely neglected as a source of structural design philosophy. This study lists and discusses several bio-inspired solutions classified into two main classes, i.e., compartmentalization and complexity, for structural robustness design. Different examples are provided and mechanisms are categorized and discussed in detail. Some provided ideas are already used in the current structural engineering research and practice, usually without focus on their bio-analogy. These solutions are revisited and scrutinized from a bio-inspired point of view, and new aspects and possible improvements are suggested. Moreover, novel bio-inspired concepts including delayed compartmentalization, active compartmentalization, compartmentalization in intact parts, and structural complexity are also propounded for structural design under extreme loading conditions.

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights.

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Time-Varying Spectral Kurtosis: Generalization of Spectral Kurtosis for Local Damage Detection in Rotating Machines under Time-Varying Operating Conditions.

Vibration-based local damage detection in rotating machines (i.e., rolling element bearings) is typically a problem of detecting low-energy cyclic impulsive modulations in the measured signal. This can be challenging as both the amplitude of a single damage-related impulse and the distance between impulses might be changing in time. From the signal processing point of view, this means time varying regarding the the signal-to-noise ratio, location of information in the frequency domain, and loss of periodicity (this remains cyclic but not periodic). One of the many attempted approaches to this problem is filtration using custom filters derived in a data-driven fashion. One of the methods to obtain such filters is a selector approach, where the value of a certain statistic is calculated for individual frequency bands of a signal that results in the magnitude response of a filter. In this approach, each chosen statistic will yield different results, and the obtained filter will be focused on different frequency bands focusing on different behaviors. One of the most popular and powerful selectors is spectral kurtosis as popularized by Antoni, which uses kurtosis as an operational statistic. Unfortunately, after closer inspection, it is easy to notice that, although selectors can significantly enhance the signal, they accumulate a great deal of noise and other background content of signals, which occupies the space (or rather time) in between the impulses. Another disadvantage is that such filters are time-invariant, because, in the principle of their construction, they are not adaptive, and even slight changes in the signal yield suboptimal results either by missing relevant data when the conditions in the signal change (i.e., informative impulses widen in bandwidth), or by accumulating unnecessary noise when the relevant information is not present (in between impulses or in frequency bands that impulses no longer occupy). To address this issue, I propose generalization of the selector approach using the example of spectral kurtosis. This assumes creating a time-varying selector that can be seen as a spatial filter in the time-frequency domain. The time-varying SK (TVSK) is estimated for segments of the signal, and, instead of a vector of SK-based filter coefficients, one obtains a TVSK-based matrix of coefficients that takes into account the time-varying properties of the signal. The obtained structure is then binarized and used as a filter. The presented method is tested using a simulated signal as well as two real-life signals measured on heavy-duty bearings in two different types of machine.

Observation of Bothrops atrox snake envenoming blister formation from five patients: pathophysiological insights

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Local Defect Detection in Bearings in the Presence of Heavy-Tailed Noise and Spectral Overlapping of Informative and Non-Informative Impulses.

The problem of the informative frequency band (IFB) selection for local fault detection is considered in the paper. There are various approaches that are very effective in this issue. Most of the techniques are vibration-based and they are related to the cyclic impulses detection (associated with the local fault) in the background noise. However, when the background noise in the vibration signal has non-Gaussian impulsive behavior, the classical methods seem to be insufficient. Recently, new techniques were proposed by several authors and interesting approaches were tested for different non-Gaussian signals. We demonstrate the comparative analysis related to the results for three selected techniques proposed in recent years, namely the Alpha selector, Conditional Variance-based selector, and Spearman selector. The techniques seem to be effective for the IFB selection for the non-Gaussian distributed vibration signals. The main purpose of this article is to investigate how spectral overlapping of informative and non-informative impulsive components will affect diagnostic procedures. According to our knowledge, this problem was not considered in the literature for the non-Gaussian signals. Nevertheless, as we demonstrated by the simulations, the level of overlapping and the location of a center frequency of the mentioned frequency bands have a significant influence on the behavior of the considered selectors. The discussion about the effectiveness of each analyzed method is conducted. The considered problem is supported by real-world examples.

Three-dimensional numerical simulation of soft-tissue wound healing using constrained-mixture anisotropic hyperelasticity and gradient-enhanced damage mechanics.

Healing of soft biological tissues is the process of self-recovery or self-repair after injury or damage to the extracellular matrix (ECM). In this work, we assume that healing is a stress-driven process, which works at recovering a homeostatic stress metric in the tissue by replacing the damaged ECM with a new undamaged one. For that, a gradient-enhanced continuum healing model is developed for three-dimensional anisotropic tissues using the modified anisotropic Holzapfel-Gasser-Ogden constitutive model. An adaptive stress-driven approach is proposed for the deposition of new collagen fibres during healing with orientations assigned depending on the principal stress direction. The intrinsic length scales of soft tissues are considered through the gradient-enhanced term, and growth and remodelling are simulated by a constrained-mixture model with temporal homogenization. The proposed model is implemented in the finite-element package Abaqus by means of a user subroutine UEL. Three numerical examples have been achieved to illustrate the performance of the proposed model in simulating the healing process with various damage situations, converging towards stress homeostasis. The orientations of newly deposited collagen fibres and the sensitivity to intrinsic length scales are studied through these examples, showing that both have a significant impact on temporal evolutions of the stress distribution and on the size of the damage region. Applications of the approach to carry out in silico experiments of wound healing are promising and show good agreement with existing experiment results.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

BACKGROUND: Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. OBJECTIVES: This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. METHODS: The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. RESULTS: The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. CONCLUSIONS: Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. 50:576-589, 2018. © 2018 Wiley Periodicals, Inc.

Photodynamic therapy for actinic keratosis: Is the European consensus protocol for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?

BACKGROUND: Topical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. OBJECTIVES: In this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT - with the exposure is assumed to be performed during either a clear sunny day or an overcast day - in the treatment of AK with methyl aminolevulinate through a mathematical modeling. METHOD: This already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. RESULTS: The European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. CONCLUSIONS: Results analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128.

A new approach to local DCO in ankle fracture dislocations: external fixation with diaphyseal unicortical screws applied by local anaesthesia.

PURPOSE: Ankle fracture dislocations represent a great threat for soft tissue viability and articular instability. The use of a temporary ankle bridging ExFix plays a fundamental role in the local damage control orthopaedics while waiting for definitive synthesis. METHODS: For this prospective research, we have developed a full application protocol of innovative diaphyseal monocortical screws fixator (Unyco-OrthofixTM) exclusively under local anaesthesia. Rigid selection criteria allowed us to collect nine patients during a period of almost 2 years. VAS score was analysed for the feasibility of the procedure, and a thorough radiologic evaluation was performed. RESULTS: Results pointed out that the calcaneus pin insertion (VAS: 3.44) followed by the local anaesthetics injection (VAS: 3.22) was the most painful, without precluding to continue the procedure; fracture temporary stability was achieved in all the cases. CONCLUSIONS: The procedure of monocortical diaphyseal application in bridging external fixation is comparable to the conventional transcalcaneal traction maintaining the advantage in terms of speediness, independence from anaesthetists and feasibility within few minutes from hospital admittance even in patients under anticoagulants therapy, but increasing the stability of the reduction and improving the quality of nursing (so-called portable traction).

Intradermal injection of Bothrops cotiara venom in mice in an experimental wound model

Bothropic envenomation induces hemorrhage, coagulant disturbances and necrosis. Regarding therapies against the local damage caused by the venom, there is little information on tissue changes until the complete healing. In the current study, local damage was evaluated by examination of morphological inflammatory alterations, mast cell count, and analysis of collagen deposition. Bleeding was evident four hours after inoculation. After 24 hours, a large area of injury appeared presenting disorganized tissue, significant hemorrhage and acute inflammation. After three days, the damaged area was extensive, with a large amount of inflammatory cells and the presence of scab. In seven days, healing and reepithelization process started. And, 21 days later, the epithelium showed less infiltration and no skin appendages. The number of mast cells was similar to control after four hours, with a drop of 50 percent at 24 hours, followed by an increase until the 21st day. No differences of collagen deposition were observed among experimental groups. Taken together, wound healing after intradermal injection of Bothrops cotiara venom in mice follows similar parameters to wounds caused by other bothropic venoms. The present work reveals the importance of experimental wound models to the study of neutralizing agents against venom toxins.