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Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

ABSTRACT: Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon.

SUBMITTER: Connizzo BK

PROVIDER: S-EPMC4885754 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

Connizzo Brianne K BK Adams Sheila M SM Adams Thomas H TH Jawad Abbas F AF Birk David E DE Soslowsky Louis J LJ

Journal of biomechanics 20160402 9

Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression ...[more]

PMID: 27067362

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Project description:INTRODUCTION:Hyperglycemia in pregnancy (HIP, including gestational diabetes and pre-existing type 1 and type 2 diabetes) is increasing, with associated risks to the health of women and their babies. Strategies to manage and prevent this condition are contested. Dynamic simulation models (DSM) can test policy and program scenarios before implementation in the real world. This paper reports the development and use of an advanced DSM exploring the impact of maternal weight status interventions on incidence of HIP. METHODS:A consortium of experts collaboratively developed a hybrid DSM of HIP, comprising system dynamics, agent-based and discrete event model components. The structure and parameterization drew on a range of evidence and data sources. Scenarios comparing population-level and targeted prevention interventions were simulated from 2018 to identify the intervention combination that would deliver the greatest impact. RESULTS:Population interventions promoting weight loss in early adulthood were found to be effective, reducing the population incidence of HIP by 17.3% by 2030 (baseline ('business as usual' scenario)=16.1%, 95%?CI 15.8 to 16.4; population intervention=13.3%, 95%?CI 13.0 to 13.6), more than targeted prepregnancy (5.2% reduction; incidence=15.3%, 95%?CI 15.0 to 15.6) and interpregnancy (4.2% reduction; incidence=15.5%, 95%?CI 15.2 to 15.8) interventions. Combining targeted interventions for high-risk groups with population interventions promoting healthy weight was most effective in reducing HIP incidence (28.8% reduction by 2030; incidence=11.5, 95%?CI 11.2 to 11.8). Scenarios exploring the effect of childhood weight status on entry to adulthood demonstrated significant impact in the selected outcome measure for glycemic regulation, insulin sensitivity in the short term and HIP in the long term. DISCUSSION:Population-level weight reduction interventions will be necessary to 'turn the tide' on HIP. Weight reduction interventions targeting high-risk individuals, while beneficial for those individuals, did not significantly impact forecasted HIP incidence rates. The importance of maintaining interventions promoting healthy weight in childhood was demonstrated.

Dataset Information

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

Publications

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

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