A novel whole "Joint-in-Motion" device reveals a permissive effect of high glucose levels and mechanical stress on joint destruction.

OBJECTIVE: Osteoarthritis (OA) has recently been suggested to be associated with diabetes. However, this association often disappears when accounting for body mass index (BMI), suggesting that mechanical stress may be a confounding factor. We investigated the combined influence of glucose level and loading stress on OA progression using a novel whole joint-in-motion (JM) culture system. DESIGN: Whole mouse knee joints were placed in an enclosed chamber with culture media and actuated to recapitulate leg movement, with a dynamic stress regimen of 0.5 Hz, 8 h/day for 7 days. These joints were treated with varying levels of glucose and controlled for osmolarity and diffusion. Joint movement and joint space were examined by X-ray fluoroscopy and microCT. Cartilage matrix levels were quantified by blinded Mankin scoring and immunohistochemistry. RESULTS: Culturing in the JM device facilitated proper leg extension and flexion movements, and adequate mass transport for analyzing the effect of glucose on cartilage. Treatment with higher levels of glucose either via media supplementation or intra-articular injection caused a significant decrease in levels of glycosaminoglycan (GAG) and an increase in aggrecan neoepitope in articular cartilage, but only under dynamic stress. Additionally, collagen II level was slightly reduced by high glucose levels. CONCLUSIONS: High levels of glucose and dynamic stress have permissive effects on articular cartilage GAG loss and aggrecan degradation, implicating that mechanical stress confounds the association of diabetes with OA. The JM device supports novel investigation of mechanical stress on the integrity of an intact living mouse joint to provide insights into OA pathogenesis.

Variation in COVID-19 outbreaks at the US state and county levels.

OBJECTIVE: The COVID-19 pandemic poses an unprecedented threat to the health and economic prosperity of the world's population. Yet, because not all regions are affected equally, this research aims to understand whether the relative growth rate of the initial outbreak in early 2020 varied significantly between the US states and counties. STUDY DESIGN: Based on publicly available case data from across the USA, the initial outbreak is statistically modeled as an exponential curve. METHODS: Regional differences are visually compared using geo maps and spaghetti lines. In addition, they are statistically analyzed as an unconditional model (one-way random effects analysis of variance estimated with HLM 7.03); the bias between state- and county-level models is evidenced with distribution tests and Bland-Altman plots (using SPSS 26). RESULTS: At the state level, the outbreak rate follows a normal distribution with an average relative growth rate of 0.197 (doubling time 3.518 days). But there is a low degree of reliability between state-wide and county-specific data reported (Intraclass correlation coefficient ICC = 0.169, P < 0.001), with a bias of 0.070 (standard deviation 0.062) as shown with a Bland-Altman plot. Hence, there is a significant variation in the outbreak between the US states and counties. CONCLUSIONS: The results emphasize the need for policy makers to look at the pandemic from the smallest population subdivision possible, so that countermeasures can be implemented, and critical resources provided effectively. Further research is needed to understand the reasons for these regional differences.

Actin filament length tunes elasticity of flexibly cross-linked actin networks.

Networks of the cytoskeletal biopolymer actin cross-linked by the compliant protein filamin form soft gels that stiffen dramatically under shear stress. We demonstrate that the elasticity of these networks shows a strong dependence on the mean length of the actin polymers, unlike networks with small, rigid cross-links. This behavior is in agreement with a model of rigid filaments connected by multiple flexible linkers.

Nonlinear elasticity of stiff biopolymers connected by flexible linkers.

Networks of the biopolymer actin, cross-linked by the compliant protein filamin, form soft gels. They can, however, withstand large shear stresses due to their pronounced nonlinear elastic behavior. The nonlinear elasticity can be controlled by varying the number of cross-links per actin filament. We propose and test a model of rigid filaments decorated by multiple flexible linkers that is in quantitative agreement with experiment. This allows us to estimate loads on individual cross-links, which we find to be less than 10 pN.

A quantitative comparison of a position measurement system and accelerometry.

An electro-mechanical system to characterize the dynamic performance of a position measurement system was constructed. The system produced pure sine wave kinematics over the frequency range of 1-11 Hz. Synchronous measurements of the position (using infra-red light emitting diodes) and the acceleration were taken at discrete frequencies. The position signal was filtered and differentiated twice to obtain an estimated acceleration. The acceleration estimate was compared to the acceleration reading from the accelerometer, and both were compared to the theoretical acceleration. The comparison was based on extracting average features of the signal like amplitude, offset and noise. The results show that the accelerometer measurements matched the theoretical amplitude to within 1-3% over most of the range but showed significant offset drift. The acceleration estimates based on the position measurements were highly dependent on the filtering scheme, showed no significant offset but had higher levels of noise. The experimental measurements and the mathematical analysis quantitatively compared the dynamic performance of the position measurement system and the accelerometer. Such a system could be used to optimize the performance of position measurement devices, by comparing different filtering and/or differentiating schemes.