Mathematical modeling to understand the role of bivalent thrombin-fibrin binding during polymerization.

Thrombin is an enzyme produced during blood coagulation that is crucial to the formation of a stable clot. Thrombin cleaves soluble fibrinogen into fibrin, which polymerizes and forms an insoluble, stabilizing gel around the growing clot. A small fraction of circulating fibrinogen is the variant γA/γ', which has been associated with high-affinity thrombin binding and implicated as a risk factor for myocardial infarctions, deep vein thrombosis, and coronary artery disease. Thrombin is also known to be strongly sequestered by polymerized fibrin for extended periods of time in a way that is partially regulated by γA/γ'. However, the role of γA/γ'-thrombin interactions during fibrin polymerization is not fully understood. Here, we present a mathematical model of fibrin polymerization that considered the interactions between thrombin, fibrinogen, and fibrin, including those with γA/γ'. In our model, bivalent thrombin-fibrin binding greatly increased thrombin residency times and allowed for thrombin-trapping during fibrin polymerization. Results from the model showed that early in fibrin polymerization, γ' binding to thrombin served to localize the thrombin to the fibrin(ogen), which effectively enhanced the enzymatic conversion of fibrinogen to fibrin. When all the fibrin was fully generated, however, the fibrin-thrombin binding persisted but the effect of fibrin on thrombin switched quickly to serve as a sink, essentially removing all free thrombin from the system. This dual role for γ'-thrombin binding during polymerization led to a paradoxical decrease in trapped thrombin as the amount of γ' was increased. The model highlighted biochemical and biophysical roles for fibrin-thrombin interactions during polymerization and agreed well with experimental observations.

Fat-Free Mass and the Balance Error Scoring System Predict an Appropriate Maximal Load in the Unilateral Farmer's Walk.

This study quantified and compared unilateral farmer's walk (UFW) performance in recreationally active males and females, and determined if additional variables allowed for the prediction of a maximal safe load. Anthropometric (height, body weight (BW), body mass index, body fat percentage, fat-free mass (FFM), and fat mass), muscular endurance (maximal duration side bridge), and balance (Balance Error Scoring System (BESS)) tests were completed. Participants performed a series of 20 s UFW trials (non-dominant side) at a cadence of 66 beats/min. The initial load was 10% of BW and increased by 10% per trial until deviations in spinal alignment or compromised gait patterns were noted, and the series was terminated. The highest load carried before technical failure was recorded. Descriptive and comparative statistics and a stepwise linear regression analysis were utilized to determine relationships between UFW performance and anthropometric, muscular endurance, and balance tests. Males (N = 25) were significantly taller (177.3 ± 6.7 vs. 164.7 ± 7.2 cm, p < 0.05), heavier (81.7 ± 7.0 vs. 62.0 ± 9.4 kg, p < 0.05), and leaner (14.4 ± 4.4 vs. 22.4 ± 4.8%, p < 0.05) than females (N = 26). Further, males had a higher amount of FFM (p < 0.05) than females. The males (52.2 ± 9.0, 64% BW) carried a higher average UFW load than the females (32.5 ± 7.1 kg, 53% BW, p < 0.05). FFM was strongly predictive of UFW load (load = -9.88876 + 0.88679 × (FFM); r² = 0.774, p < 0.0001). The addition of the BESS test further increased the accuracy of the prediction equation (r² = 0.800, p < 0.0001). There are differences in UFW performance ability between males and females. As our method does not account for all potential confounding variables, the use of these equations should be combined with technique analysis and participant feedback to ensure an appropriate workload.