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Background: Amyloid-β plaques (Aβ) are associated with Alzheimer’s disease (AD). Pooled assessment of amyloid reduction in transgenic AD mice is critical for expediting anti-amyloid AD therapeutic research. Objective: The mean threshold of Aβ reduction necessary to achieve cognitive improvement was measured via pooled assessment (n = 594 mice) of Morris water maze (MWM) escape latency of transgenic AD mice treated with substances intended to reduce Aβ via reduction of beta-secretase cleaving enzyme (BACE). Methods: Machine learning and statistical methods identified necessary amyloid reduction levels using mouse data (e.g., APP/PS1, LPS, Tg2576, 3xTg-AD, control, wild type, treated, untreated) curated from 22 published studies. Results: K-means clustering identified 4 clusters that primarily corresponded with level of Aβ: untreated transgenic AD control mice, wild type mice, and two clusters of transgenic AD mice treated with BACE inhibitors that had either an average 25% “medium reduction” of Aβ or 50% “high reduction” of Aβ compared to untreated control. A 25% Aβ reduction achieved a 28% cognitive improvement, and a 50% Aβ reduction resulted in a significant 32% improvement compared to untreated transgenic mice (p < 0.05). Comparatively, wild type mice had a mean 41% MWM latency improvement over untreated transgenic mice (p < 0.05). BACE reduction had a lesser impact on the ratio of Aβ42 to Aβ40. Supervised learning with an 80% –20% train-test split confirmed Aβ reduction was a key feature for predicting MWM escape latency (R2 = 0.8 to 0.95). Conclusions: Results suggest a 25% reduction in Aβ as a meaningful treatment threshold for improving transgenic AD mouse cognition. 

Abstract The purpose of this computational study was to investigate the effects of neonate-focused clinical delivery maneuvers on brachial plexus (BP) during shoulder dystocia. During shoulder dystocia, the anterior shoulder of the neonate is obstructed behind the symphysis pubis of the maternal pelvis, postdelivery of the neonate's head. This is managed by a series of clinical delivery maneuvers. The goal of this study was to simulate these delivery maneuvers and study their effects on neonatal BP strain. Using madymo models of a maternal pelvis and a 90th-percentile neonate, various delivery maneuvers and positions were simulated including the lithotomy position alone of the maternal pelvis, delivery with the application of various suprapubic pressures (SPPs), neonate in an oblique position, and during posterior arm delivery maneuver. The resulting BP strain (%) along with the required maternal delivery force was reported in these independently simulated scenarios. The lithotomy position alone served as the baseline. Each of the successive maneuvers reported a decrease in the required delivery force and resulting neonatal BP strain. As the applied SPP force increased (three scenarios simulated), the required maternal delivery force and neonatal BP strain decreased. A further decrease in both delivery force and neonatal BP strain was observed in the oblique position, with the lowest delivery force and neonatal BP strain reported during the posterior arm delivery maneuver. Data obtained from the improved computational models in this study enhance our understanding of the effects of clinical maneuvers on neonatal BP strain during complicated birthing scenarios such as shoulder dystocia. 

The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking. 

Abstract Background Characterizing the biomechanical failure responses of neonatal peripheral nerves is critical in understanding stretch-related peripheral nerve injury mechanisms in neonates. Objective This in vitro study investigated the effects of prestretch magnitude and duration on the biomechanical failure behavior of neonatal piglet brachial plexus (BP) and tibial nerves. Methods BP and tibial nerves from 32 neonatal piglets were harvested and prestretched to 0, 10, or 20% strain for 90 or 300 seconds. These prestretched samples were then subjected to tensile loading until failure. Failure stress and strain were calculated from the obtained load-displacement data. Results Prestretch magnitude significantly affected failure stress but not the failure strain. BP nerves prestretched to 10 or 20% strain, exhibiting significantly lower failure stress than those prestretched to 0% strain for both prestretch durations (90 and 300 seconds). Likewise, tibial nerves prestretched to 10 or 20% strain for 300 seconds, exhibiting significantly lower failure stress than the 0% prestretch group. An effect of prestretch duration on failure stress was also observed in the BP nerves when subjected to 20% prestretch strain such that the failure stress was significantly lower for 300 seconds group than 90 seconds group. No significant differences in the failure strains were observed. When comparing BP and tibial nerve failure responses, significantly higher failure stress was reported in tibial nerve prestretched to 20% strain for 300 seconds than BP nerve. Conclusion These data suggest that neonatal peripheral nerves exhibit lower injury thresholds with increasing prestretch magnitude and duration while exhibiting regional differences. 

Abstract Despite occurrence of neonatal hypoxia and peripheral nerve injuries in complicated birthing scenarios, the effect of hypoxia on the biomechanical responses of neonatal peripheral nerves is not studied. In this study, neonatal brachial plexus and tibial nerves, obtained from eight normal and eight hypoxic 3-5 days old piglets, were tested in uniaxial tension until failure at a rate of 0.01 mm/s or 10 mm/s. Failure load, stress, and modulus of elasticity were reported to be significantly lower in hypoxic neonatal brachial plexus (BP) and tibial nerves than respective normal tissue at both 0.01 and 10 mm/s rates. Failure strain was significantly lower in the hypoxic neonatal BP nerves only at 10 mm/s rate when compared to normal BP nerve. This is the first available data that indicates weaker mechanical behavior of hypoxic neonatal peripheral nerves as compared to normal tissue, and offers an understanding of the biomechanical responses of peripheral nerves of hypoxic neonatal piglets. 

Abstract Brachial plexus birth injury has a reported incidence of 1 to 4 per 1000 live births. During complicated deliveries, neonatal, maternal, and other birth-related factors can cause over-stretching or avulsion of the neonatal brachial plexus leading to injury. Understanding biomechanical responses of the neonate brachial plexus when subjected to stretch can offer insight into the injury outcomes while guiding the development of preventative maneuvers that can help reduce the occurrence of neonatal brachial plexus injuries. This review article aims to offer a comprehensive overview of existing literature reporting biomechanical responses of the brachial plexus, in both adults and neonates, when subjected to stretch. Despite the discrepancies in the reported biomechanical properties of the brachial plexus, the studies confirm the loading rate and loading direction dependency of the brachial plexus tissue. Future studies, possibly in vivo, that utilize clinically-relevant neonatal large animal models can provide translational failure values of the biomechanical parameters for the neonatal brachial plexus when subjected to stretch. 

Background: Apolipoprotein E (APOE) genotypes typically increase risk of amyloid-β deposition and onset of clinical Alzheimer’s disease (AD). However, cognitive assessments in APOE transgenic AD mice have resulted in discord. Objective: Analysis of 31 peer-reviewed AD APOE mouse publications (n = 3,045 mice) uncovered aggregate trends between age, APOE genotype, gender, modulatory treatments, and cognition. Methods: T-tests with Bonferroni correction (significance = p < 0.002) compared age-normalized Morris water maze (MWM) escape latencies in wild type (WT), APOE2 knock-in (KI2), APOE3 knock-in (KI3), APOE4 knock-in (KI4), and APOE knock-out (KO) mice. Positive treatments (t+) to favorably modulate APOE to improve cognition, negative treatments (t–) to perturb etiology and diminish cognition, and untreated (t0) mice were compared. Machine learning with random forest modeling predicted MWM escape latency performance based on 12 features: mouse genotype (WT, KI2, KI3, KI4, KO), modulatory treatment (t+, t–, t0), mouse age, and mouse gender (male = g_m; female = g_f, mixed gender = g_mi). Results: KI3 mice performed significantly better in MWM, but KI4 and KO performed significantly worse than WT. KI2 performed similarly to WT. KI4 performed significantly worse compared to every other genotype. Positive treatments significantly improved cognition in WT, KI4, and KO compared to untreated. Interestingly, negative treatments in KI4 also significantly improved mean MWM escape latency. Random forest modeling resulted in the following feature importance for predicting superior MWM performance: [KI3, age, g_m, KI4, t0, t+, KO, WT, g_mi, t–, g_f, KI2] = [0.270, 0.094, 0.092, 0.088, 0.077, 0.074, 0.069, 0.061, 0.058, 0.054, 0.038, 0.023]. Conclusion: APOE3, age, and male gender was most important for predicting superior mouse cognitive performance.