Measurement of intracellular strain on deformable substrates with texture correlation

Mechanical stimuli are important factors that regulate cell proliferation, survival, metabolism and motility in a variety of cell types. The relationship between mechanical deformation of the extracellular matrix and intracellular deformation of cellular sub-regions and organelles has not been fully elucidated, but may provide new insight into the mechanisms involved in transducing mechanical stimuli to biological responses. In this study, a novel fluorescence microscopy and image analysis method was applied to examine the hypothesis that mechanical strains are fully transferred from a planar, deformable substrate to cytoplasmic and intranuclear regions within attached cells. Intracellular strains were measured in cells derived from the anulus fibrosus of the intervertebral disc when attached to an elastic silicone membrane that was subjected to tensile stretch. Measurements indicated cytoplasmic strains were similar to those of the underlying substrate, with a strain transfer ratio (STR) of 0.79. In contrast, nuclear strains were much smaller than those of the substrate, with an STR of 0.17. These findings are consistent with previous studies indicating nuclear stiffness is significantly greater than cytoplasmic stiffness, as measured using other methods. This study provides a novel method for the study of cellular mechanics, including a new technique for measuring intranuclear deformations, with evidence of differential magnitudes and patterns of strain transferred from the substrate to cell cytoplasm and nucleus.     

NR2A-containing NMDA receptors depress glutamatergic synaptic transmission and evoked-dopamine release in the mouse striatum

NMDA receptors play essential roles in the physiology and pathophysiology of the striatum, a brain nucleus involved in motor control and reward-motivated behaviors. NMDA receptors are composed of NR1 and NR2A–D subunits. Functional properties of NMDA receptors are determined by the type of NR2 subunit they contain. In this study, we have examined the involvement of NR2B and NR2A in the modulatory effect of NMDA on glutamatergic and dopaminergic synaptic transmission in the striatum. We found that bath application of NMDA decreased the amplitude of the field excitatory post-synaptic potential/population spike (fEPSP/PS) measured in corticostriatal mouse brain slices. This depression was not affected by the NR2B-selective antagonists Ifenprodil and Ro 25-6981, but was abolished by the NR2A antagonist NVP-AAM077. Activation of corticostriatal neurons by NMDA did not contribute to synaptic depression because similar results were obtained in decorticated striatal slices. Synaptic depression was not dependent on GABA release because the GABA_A receptor antagonist bicuculline did not affect NMDA-induced decrease of the fEPSP/PS. NMDA also depressed evoked-dopamine release through NR2A- but not NR2B-containing NMDA receptors. Our results identify an important role for NR2A-containing NMDA receptors intrinsic to the striatum in regulating glutamatergic synaptic transmission and evoked-dopamine release.     

Are hamstrings activated to counteract shear forces during isometric knee extension efforts in healthy subjects?

The hamstring muscles have the potential to counteract anterior shear forces at the knee joint by co-contracting during knee extension efforts. Such a muscle recruitment pattern might protect the anterior cruciate ligament (ACL) by reducing its strain. In this study we investigated to what extent co-activation of the knee flexors during extension efforts is compatible with the hypothesis that this co-activation serves to counteract anterior tibial shear forces during isometric knee extension efforts in healthy subjects. To this aim, it is investigated whether co-activation varies with the required knee extension moment, with the knee joint angle, and with the position of the external flexing force relative to the knee joint. With unaltered moment and muscle activation, distal positioning of the flexing force on the tibia causes higher resultant (muscular plus external) forward shear forces at the knee as compared to proximal positioning. In ten subjects, knee flexor and extensor EMG was measured during a quasi-isometric positioning task for a range (5-50 degrees) of knee flexion angles. It was found that the co-activation of the knee flexors increased with the extension moment, but this increase was less than proportional (p<0.001). The extension moment increased 2.7 to 3.4 times, whereas the activation of Biceps Femoris and Semitendinosus increased only a factor 1.3 to 2.0 (joint angle dependent). Furthermore, a strong increase in co-activation was seen near full extension of the knee joint. The position of the external extension load on the tibia did not affect the level of co-contraction. It is argued that these results do not suggest a recruitment pattern that is directed at reduction of anterior shear forces in the knee joint during sub-maximal isometric knee extension efforts in healthy subjects.     

Preoperative Physical Activity Level Has No Relationship to the Degree of Recovery One Year after Primary Total Hip or Knee Arthroplasty: A Cohort Study

Background

When it comes to prevalidation, it is assumed that a higher preoperative level of physical activity leads to better postoperative recovery. However current literature is inconclusive about the effect of prevalidation on functional recovery of patients with primary osteoarthritis (OA) who underwent a THA or TKA. Therefore the aim of this study is to analyse one of the major assumptions underlying the potential effectiveness of prevalidation namely the relationship between preoperative physical activity level and postoperative recovery one year after THA or TKA in a group of 658 OA patients.

Methods and Results

From 2006 to 2012, 1061 patients underwent a primary THA or TKA at University Medical Center Groningen. Preoperative and one-year postoperative patients filled in the SQUASH questionnaire to get an impression of their physical activity level, and the WOMAC questionnaire to obtain insight into degree of recovery. Missing data were multiply imputed. No relationship was found between the preoperative total (B-coefficient = 0.03, CI95% = −0.033–0.093) and leisure-time physical activity level (B-coefficient = 0.042, CI95% = −0.009–0.093) neither for preoperative compliance with the Dutch Recommendation for Health-Enhancing Physical Activity (B-coefficient = 0.002, CI95% = −0.053–0.057), and the degree of recovery one year after surgery.

Conclusion

The preoperative physical activity level had no relation with the degree of recovery one year after THA or TKA. The results do not support one of the major assumptions behind prevalidation, which assumes that a higher preoperative physical activity level will lead to a better recovery after THA or TKA.     

The Relation between Gray Matter Morphology and Divergent Thinking in Adolescents and Young Adults

Adolescence and early adulthood are developmental time periods during which creative cognition is highly important for adapting to environmental changes. Divergent thinking, which refers to generating novel and useful solutions to open-ended problems, has often been used as a measure of creative cognition. The first goal of this structural neuroimaging study was to elucidate the relationship between gray matter morphology and performance in the verbal (AUT; alternative uses task) and visuo-spatial (CAT; creative ability test) domain of divergent thinking in adolescents and young adults. The second goal was to test if gray matter morphology is related to brain activity during AUT performance. Neural and behavioral data were combined from a cross-sectional study including 25 adolescents aged 15–17 and 20 young adults aged 25–30. Brain-behavior relationships were assessed without a priori location assumptions and within areas that were activated during an AUT-scanner task. Gray matter volume and cortical thickness were not significantly associated with verbal divergent thinking. However, visuo-spatial divergent thinking (CAT originality and fluency) was positively associated with cortical thickness of the right middle temporal gyrus and left brain areas including the superior frontal gyrus and various occipital, parietal, and temporal areas, independently of age. AUT brain activity was not associated with cortical thickness. The results support an important role of a widespread brain network involved in flexible visuo-spatial divergent thinking, providing evidence for a relation between cortical thickness and visuo-spatial divergent thinking in adolescents and young adults. However, studies including visuo-spatial divergent thinking tasks in the scanner are warranted.     

Three-dimensional registration of histology of human atherosclerotic carotid plaques to in-vivo imaging

An accurate spatial relationship between 3D in-vivo carotid plaque and lumen imaging and histological cross sections is required to study the relationship between biomechanical parameters and atherosclerotic plaque components. We present and evaluate a fully three-dimensional approach for this registration problem, which accounts for deformations that occur during the processing of the specimens. By using additional imaging steps during tissue processing and semi-automated non-linear registration techniques, a 3D-reconstruction of the histology is obtained.The methodology was evaluated on five specimens obtained from patients, operated for severe atherosclerosis in the carotid bifurcation. In more than 80% of the histology slices, the quality of the semi-automated registration with computed tomography angiography (CTA) was equal to or better than the manual registration. The inter-observer variability was between one and two in-vivo CT voxels and was equal to the manual inter-observer variability. Our technique showed that the angles between the normals of the registered histology slices and the in-vivo CTA scan direction ranged 6–56°, indicating that proper 3D-registration is crucial for establishing a correct spatial relation with in-vivo imaging modalities. This new 3D-reconstruction technique of atherosclerotic plaque tissue opens new avenues in the field of biomechanics as well as in the field of image processing, where it can be used for validation purposes of segmentation algorithms.