Cell proliferation and Notch signaling coordinate the formation of epithelial folds in the Drosophila leg.

The formation of complex three-dimensional organs during development requires precise coordination between patterning networks and mechanical forces. In particular, tissue folding is a crucial process that relies on a combination of local and tissue-wide mechanical forces. Here, we investigate the contribution of cell proliferation to epithelial morphogenesis using the Drosophila leg tarsal folds as a model. We reveal that tissue-wide compression forces generated by cell proliferation, in coordination with the Notch signaling pathway, are essential for the formation of epithelial folds in precise locations along the proximo-distal axis of the leg. As cell numbers increase, compressive stresses arise, promoting the folding of the epithelium and reinforcing the apical constriction of invaginating cells. Additionally, the Notch target dysfusion plays a key function specifying the location of the folds, through the apical accumulation of F-actin and the apico-basal shortening of invaginating cells. These findings provide new insights into the intricate mechanisms involved in epithelial morphogenesis, highlighting the crucial role of tissue-wide forces in shaping a three-dimensional organ in a reproducible manner.

Remote cyclic compression ameliorates myocardial infarction injury in rats via AMPK-dependent pathway.

BACKGROUND: Remote ischemic conditioning (RIC) displays a cardioprotective role in acute myocardial infarction (AMI). Since interruption of blood vessel is not an essential trigger of remote cardioprotection, tissue compression may play a prominent part in the effect. The purpose of this study was to confirm the protective effect of tissue compression on AMI and the underlying mechanisms. METHODS AND RESULTS: Rat model of AMI was induced by ligation of the left anterior descending coronary artery. Remote cyclic compression (RCC) on forelimb was applied to AMI rats for 3 days after the operation. RCC postconditioning displayed cardioprotective effects against AMI injury by limiting infarct size, alleviating cardiac dysfunction, and suppressing cardiomyocyte apoptosis. In addition, RCC postconditioning induced myocardial autophagy as evidenced by increased LC3-II and Beclin-1 and reduced mTOR levels. Furthermore, RCC treatment upregulated AMPK phosphorylation in the context of AMI hearts. AMPK inhibitor Compound C administration markedly abrogated RCC-mediated cardioprotective effect, as evidenced by decreased infarct size and cardiac function. CONCLUSION: Our results indicated that RCC postconditioning could attenuate AMI injury through inhibiting apoptosis and promoting autophagy via AMPK signaling pathway. The research provided a novel perspective for studying the cardioprotection of RIC and possible therapeutic strategy for managing AMI injury.

Effects of different intensities of intermittent pneumatic soft-tissue compression on bone defect repair.

BACKGROUND: To estimate the effects of different intensities of intermittent pneumatic soft-tissue compression on bone defect repair in an animal model. METHODS: Five mm radial bone defect in length was made in 64 mature New Zealand rabbits and all animals randomly assigned into four groups: Group A (control group without compression), Group B (5-7 kPa intensity), Group C (8-10 kPa intensity) and Group D (11-13 kPa intensity). On the fourth day after surgery, their legs were intermittently pneumatic compressed for 4 weeks. The stimulation lasted 30 min every day and the frequency of compression was 15 Hz. New bone formation in 4 groups was evaluated by gross observation, X-ray, Micro-CT, and histological staining at 2 and 4 weeks after surgery. RESULT: There was more new bony callus in the bone defect in group C than in other groups by gross observation and X-ray radiography at 2 and 4 weeks. The Micro-CT results showed more new bony callus, bone trabecula and higher bone mineral density in group C. Fluorescent labeling results showed the speed of new bone formation in Group C was faster than that in other groups, among which the control group had the slowest speed of new bone formation. The result of histology had shown that the trabeculae in bone callus in group C had a regular form, the trabeculae were wide and had a more become osteoblast around them. CONCLUSION: The intermittent pneumatic soft-tissue compression can accelerate new bone formation of bone defects and the optimal intensity is 8-10 kPa for repairing the rabbit radial bone defect.

Evaluation of the Effect of Tissue Compression on the Results of Shear Wave Elastography Measurements.

Shear wave imaging is considered to be more precise and less operator dependent when compared with strain imaging. It enables quantitative and reproducible data (Young's modulus of the imaged tissue). However, results of shear wave imaging can be affected by a variety of different factors. The aim of this study is to evaluate the effect of the pressure applied by the ultrasound probe during examination on the measured values of Young's modulus. The effect of the tissue compression on the results of the real-time shear wave elastography was evaluated via the gelatine phantom measurements, via the ex vivo experiments with pig liver, and via the in vivo measurements of the thyroid gland stiffness on healthy volunteers. The results of our measurements confirmed that the measured value of Young's modulus increases with the increasing pressure applied on the imaged object. The highest increase was observed during the ex vivo experiments (400%), and the lowest increase was detected in the case of the phantom measurements (8%). A two- to threefold increase in Young's modulus was observed between the minimum and maximum pressure in the case of the in vivo elastography measurements of thyroid gland. The Veronda-Westman theoretical model was used for the description of the tissue nonlinearity. We conclude that tissue compression by the force exerted on the probe can significantly affect the results of the real-time shear wave elastography measurements. Minimum pressure should be used when measuring the absolute value of Young's modulus of superficial organs.

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues.

Quantitative validation of two model-based methods for the correction of probe pressure deformation in ultrasound.

PURPOSE: The acquisition of good quality ultrasound (US) images requires good acoustic coupling between the ultrasound probe and the patient's skin. In practice, this good coupling is achieved by the operator applying a force to the skin through the probe. This force induces a deformation of the tissues underlying the probe. The distorted images deteriorate the quality of the reconstructed 3D US image. METHODS: In this work, we propose two methods to correct these deformations. These methods are based on the construction of a biomechanical model to predict the mechanical behavior of the imaged soft tissues. The originality of the methods is that they do not use external information (force or position value from sensors, or elasticity value from the literature). The model is parameterized thanks to the information contained in the image. This is allowed thanks to the optimization of two key parameters for the model which are the indentation d and the elasticity ratio α. RESULTS: The validation is performed on real images acquired on a gelatin-based phantom using an ultrasound probe inducing an increasing vertical indentation using a step motor. The results showed a good correction of the two methods for indentations less than 4 mm. For larger indentations, one of the two methods (guided by the similarity score) provides a better quality of correction, presenting a Euclidean distance between the contours of the reference image and the corrected image of 0.71 mm. CONCLUSION: The proposed methods ensured the correction of the deformed images induced by a linear probe pressure without using any information coming from sensors (force or position), or generic information about the mechanical parameters. The corrected images can be used to obtain a corrected 3D US image.

Remote Conditioning by Rhythmic Compression of Limbs Ameliorated Myocardial Infarction by Downregulation of Inflammation via A2 Adenosine Receptors.

Background: Remote ischemic conditioning (RIC) is a cardioprotective phenomenon, yet transient ischemia is not a requisite trigger for remote cardioprotection. In fact, RIC is a stimulus compound containing interruption of the blood vessel and tissue compression. In this study, we evaluate the effects of remote tissue compression on infarct size after myocardial infarction and explore its preliminary mechanisms. Methods and Results: We used a murine model of myocardial infarction to assess ischemia injury and identified remote conditioning by rhythmic compression on forelimb as a novel cardioprotective intervention. We show that the cardioprotective signal transduction of remote conditioning from the trigger limb to the heart involves the release of adenosine. Our results demonstrate that A2a and A2b receptors are indispensable parts for cardioprotection of remote conditioning, which is linked to its anti-inflammatory properties by the subsequent activation of cAMP/PKA/NF-κB axis. Conclusion: Our results establish a new connection between remote tissue compression and cardiovascular diseases, which enhances our cognition about the role of tissue compression on RIC cardioprotection.

Mechanical Tissue Compression and Whole-mount Imaging at Single CellResolution for Developing Murine Epididymal Tubules.

Cells inside the body are subjected to various mechanical stress, such as stretch or compression provided by surrounding cells, shear stresses by blood or lymph flows, and normal stresses by luminal liquids. Force loading to the biological tissues is a fundamental method to better understand cellular responses to such mechanical stimuli. There have been many studies on compression or stretch experiments that target culture cells attached to a flexible extensible material including polydimethylsiloxane (PDMS); however, the know-how of those targeting to tissues is still incomplete. Here we present the protocol for mechanical tissue compression and image-based analysis by focusing on developing murine epididymis as an example. We show a series of steps including tissue dissection from murine embryos, hydrogel-based compression method using a manual device, and non-destructive volumetric tissue imaging. This protocol is useful for quantifying and exploring the biological mechanoresponse system at tissue level.

Computerized Cuff Pressure Algometry as Guidance for Circumferential Tissue Compression for Wearable Soft Robotic Applications: A Systematic Review.

In this article, we review the literature on quantitative sensory testing of deep somatic pain by means of computerized cuff pressure algometry (CPA) in search of pressure-related safety guidelines for wearable soft exoskeleton and robotics design. Most pressure-related safety thresholds to date are based on interface pressures and skin perfusion, although clinical research suggests the deep somatic tissues to be the most sensitive to excessive loading. With CPA, pain is induced in deeper layers of soft tissue at the limbs. The results indicate that circumferential compression leads to discomfort at ∼16-34 kPa, becomes painful at ∼20-27 kPa, and can become unbearable even below 40 kPa.

Cuff Pressure Algometry in Patients with Chronic Pain as Guidance for Circumferential Tissue Compression for Wearable Soft Exoskeletons: A Systematic Review.

In this article, we report on a systematic review of the literature on pressure-pain thresholds induced and assessed by computerized cuff pressure algometry (CPA). The motivation for this review is to provide design guidance on pressure levels for wearable soft exoskeletons and similar wearable robotics devices. In our review, we focus on CPA studies of patients who are candidates for wearable soft exoskeletons, as pain-related physiological mechanisms reportedly differ significantly between healthy subjects and patients with chronic pain. The results indicate that circumferential limb compression in patients most likely becomes painful at ∼10-18 kPa and can become unbearable even below 25 kPa. The corresponding ranges for healthy control subjects are 20-42 kPa (painful limits) and 34-84 kPa (unbearable levels). In addition, the increase of pain with time tends to be significantly higher, and the adaptation to pain significantly lower, than in healthy subjects. The results of this review provide guidance to designers of wearable robotics for populations with chronic pain regarding rates and magnitudes of tissue compression that may be unacceptable to users.

Changes in Small Intestine Tissue Compressed by a Linear Stapler Based on Cole Y Model.

Clarifying changes in gastrointestinal tissue compressed by surgical stapler is a crucial prerequisite for stapler design optimization. For this study, a stapler was modified, and multifrequency bioimpedance of a porcine small intestine tissue compressed by the stapler was measured. The Cole Y model was fitted to the bioimpedance, and changes in tissue were analyzed using model parameters: G 0, extracellular fluid conductance; ΔG, intracellular fluid conductance; C cpeF, equivalent capacitance of cell membrane. The changes could be divided into two stages: first, all parameters decreased sharply with slopes more than 15.70 ± 2.67, 4.25 ± 1.23 µS/s and 72.68 ± 6.99 pF/s respectively; and subsequently, with an increase in compression strength, G 0 decreased with slopes less than 2.54 ± 0.40 µS/s, ΔG decreased slightly with slope of 0.26 ± 0.04 µS/s after fluctuating mildly, and C cpeF remained nearly invariant after initially increasing with slope of -2.94 ± 0.64 pF/s. In conclusion, when the stapler is closed, a portion of tissue is squeezed out of the measurement space, causing all parameters' sharp decrease. Subsequently, the stapler continues compressing the tissue, leading to extracellular fluid expulsion. The changes in intracellular fluid are related to the compression strength and may be explained by cell restoration. This study could provide a basis for stapler design optimization.

Modified use of methylene blue in the tissue compression technique to detect sarcocysts in meat-producing animals.

Sarcocystosis in meat-producing animals is a major cause of reduced productivity in many countries, especially those that rely on agriculture. Although several diagnostic methods are available to detect sarcocystosis, many are too time-consuming for routine use in abattoirs and meat inspection centers, where large numbers of samples need to be tested. This study aimed to compare the sensitivity of the methylene blue tissue preparation, unstained tissue preparation and nested PCR in the detection of sarcocysts in tissue samples. Approximately three-fold more sarcocysts were detected in methylene blue-stained tissue compared to unstained controls (McNemar's test: P<0.01). Test sensitivity was comparable to that of the gold standard for sarcocyst detection, nested polymerase chain reaction. These results suggest that methylene blue can be used in tissue compression as a rapid, safe, and inexpensive technique for the detection of ruminant sarcocystosis in abattoirs.

Effect of antipronation foot orthosis geometry on compression of heel and arch soft tissues.

This study aimed to understand how systematic changes in arch height and two designs of heel wedging affect soft tissues under the foot. Soft tissue thickness under the heel and navicular was measured using ultrasound. Heel pad thickness was measured when subjects were standing on a flat surface and standing on an orthosis with 4 and 8 degree extrinsic wedges and 4 mm and 8 mm intrinsic wedges (n = 27). Arch soft tissue thickness was measured when subjects were standing and when standing on an orthosis with -6 mm, standard, and +6 mm increments in arch height (n = 25). Extrinsic and intrinsic heel wedges significantly increased soft tissue thickness under the heel compared with no orthosis. The 4 and 8 degree extrinsic wedges increased tissue thickness by 28% and 27.6%, respectively, while the 4 mm and 8 mm intrinsic wedges increased thickness by 23% and 14.6%, respectively. Orthotic arch height significantly affected arch soft tissue thickness. Compared with the no orthosis condition, the -6 mm, standard, and +6 mm arch heights decreased arch tissue thickness by 9%, 10%, and 11.8%, respectively. This study demonstrates that change in orthotic geometry creates different plantar soft tissue responses that we expect to affect transmission of force to underlying foot bones.

Finite element modeling and analysis on end-to-end anastomosis of the large intestine / 医用生物力学

Objective To analyze the relationship of closed staple height with tissue damage and compression pressure, so as to provide theoretical references and guidance for the surgeon to choose the appropriate staple cartridge and height, as well as improve the safety of operation. Methods The finite element model of stapled colorectal end-to-end anastomosis was established based on analysis of staple-tissue interaction. Large intestine tissues with different wall thicknesses (1.0-1.5 mm) were compressed by closed staples with 4 different height to compare changes in stress distributions and average radial pressure. Results When the tissues were compressed by closed staple with height of 1.0, 1.1, 1.2 and 1.5 mm, respectively, the average radial stress of compressed tissues with wall thicknesses of 1.2, 1.3, 1.4, and 1.5 mm were 56.0, 58.6, 59.7 and 57.3 kPa, respectively, which was close to the optimal compression pressure. Stress concentrations were found in contact area of the staple and tissues，with the maximum stress being 2 783, 1 750, 1940 and 2 030 kPa, respectively. Conclusions Tissue damage cannot be completely avoided in anastomotic surgery, and stress concentration is generally located near contact region of the staple and tissues. The optimal closed staple height ranges in 50%-60% of the uncompressed tissue height.