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Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.
Mathematical Modelling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation
(2021)
New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle which is especially useful when time for assisted reproductive technology is limited, e.g. for emergency fertility preservation in cancer patients.
It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modelling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.
Hypokalemia, characterized by too low serum potassium levels, is a severe mineral disorder which can be life threatening. It is increasingly diagnosed in veterinarian healthcare and a topic of ongoing research. In this paper, we explore the different originating conditions of hypokalemia: reduced potassium intake, increased excretion, acid-base disturbances, or increased insulin, by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows.
Simulations are compared with literature. The results give insights into the network dynamics and point to scenarios on which experimental effort should be focused. Application of mathematical models can assist in experimental planning as well as the reduction, refinement and replacement of animal experiments.
Objectives
The clinical parameter “morning stiffness” is widely used to assess the status of rheumatoid arthritis (RA), but its accurate quantitative assessment in a clinical setting has not yet been successful. This lack of individual quantification limits both personalized medication and efficacy evaluation in the treatment of RA.
Methods
We have developed a novel technology to assess passive resistance of the metacarpophalangeal (MCP) III joint (stiffness) and its Passive Range of Motion (PRoM). Within this pilot study, nineteen female postmenopausal RA patients and nine healthy controls were examined in the evening as well as in the morning of the following day. To verify the specificity of the biomechanical quantification, eleven patients with RA were assessed both prior to and ∼3 h after glucocorticoid therapy.
Results
While the healthy controls showed only minor changes between afternoon and morning, in RA patients mean±SD PRoM decreased significantly by 18 ± 22% and stiffness increased significantly by 20 ± 18% in the morning compared with the previous afternoon. We found a significant positive correlation between RA activity and biomechanical measures. Glucocorticoids significantly increased mean PRoM by 16 ± 11% and reduced mean stiffness by 23 ± 22%.
Conclusion
This technology allowed mechanical stiffness to be quantified in MCP joints, and has demonstrated high sensitivity in respect to disease status as well as medication effect in RA patients. Such non-invasive, low risk, and rapid assessment of biomechanical joint stiffness opens a novel avenue for judging therapy efficacy in patients with RA, and potentially also in other non-RA inflammatory joint diseases.
Though gait asymmetry is used as a metric of functional recovery in clinical rehabilitation, there is no consensus on an ideal method for its evaluation. Various methods have been proposed but are limited in scope, as they can often use only positive signals or discrete values extracted from time-scale data as input. By defining five symmetry axioms, a framework for benchmarking existing methods was established and a new method was described here for the first time: the weighted universal symmetry index (wUSI), which overcomes limitations of other methods. Both existing methods and the wUSI were mathematically compared to each other and in respect to their ability to fulfill the proposed symmetry axioms. Eligible methods that fulfilled these axioms were then applied using both discrete and continuous approaches to ground reaction force (GRF) data collected from healthy gait, both with and without artificially induced asymmetry using a single instrumented elbow crutch. The wUSI with a continuous approach was the only symmetry method capable of determining GRF asymmetries in different walking conditions in all three planes of motion. When used with a continuous approach, the wUSI method was able to detect asymmetries while avoiding artificial inflation, a common problem reported in other methods. In conclusion, the wUSI is proposed as a universal method to quantify three-dimensional GRF asymmetries, which may also be expanded to other biomechanical signals.