Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA. Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples. Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs. Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

Unruptured intracranial aneurysms: relation between morphology and wall strength.

AIM OF THE STUDY: To determine the morphological features distinguishing small unruptured saccular intracranial aneurysms (sIAs) with high and low wall strength (WS) in post mortem subjects. CLINICAL RATIONALE FOR THE STUDY: Subarachnoid haemorrhage caused by sIA rupture is associated with increased mortality and morbidity. Analysis of the morphology and biomechanical properties of sIAs might facilitate the identification of clinically relevant risk factors for sIA rupture. MATERIAL AND METHODS: Eight single unruptured sIAs were found among eight subjects during 184 post mortem examinations. After assessment of the dimensions, aspect ratio (AR), size ratio (SR), height/width ratio (HW), bottleneck factor (BNF), and shape, sIAs with adjacent cerebral arteries were subjected to quasi-static increasing pressure until the wall of the cerebral artery or sIA ruptured. RESULTS: In three specimens, the sIA ruptured at a significantly lower average pressure than the other cases, in which the rupture occurred within the wall of the adjacent cerebral artery (769 vs. 1,259 mmHg; p = 0.035). The sIAs with low WS, i.e. sIAs that ruptured during experiments, were characterised by significantly increased dome dimensions compared to sIAs with high WS (p < 0.05). At the same time, no significant differences were observed between high and low WS categories regarding AR, SR, HW, and BNF, or the presence of an irregular dome shape. CONCLUSIONS AND CLINICAL IMPLICATIONS: Dome dimension was the only feature that distinguished unruptured sIAs as having low or high WS, and this supports observations that sIAs with increased dome dimensions are characterised by an increased risk of rupture. Thus, dome dimension may be more useful than other morphometric parameters, such as AR, SR, HW and BNF, in assessing the rupture risk assessment of small unruptured sIAs.

Dynamic Transcriptomic and Phosphoproteomic Analysis During Cell Wall Stress in Aspergillus nidulans.

The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth. This complex, interconnected, pathway has been only partially characterized in filamentous fungi. To better understand the dynamic cellular response to wall perturbation, a ß-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture. From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 min, respectively. To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets. Over 1800 genes were dynamically expressed and over 700 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8-4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways.

Fluid- and Biomechanical Analysis of Ascending Thoracic Aorta Aneurysm with Concomitant Aortic Insufficiency.

We present a comprehensive and original framework for the biomechanical analysis of patients affected by ascending thoracic aorta aneurysm and aortic insufficiency. Our aim is to obtain crucial indications about the role played by deranged hemodynamics on the ATAAs risk of rupture. Computational fluid dynamics analysis was performed using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow helicity and wall shear stress descriptors were assessed. A bulge inflation test was carried out in vitro on the 4 ATAAs after surgical repair. The healthy volunteers showed no eccentric blood flow, a mean TAWSS of 1.5 ± 0.3 Pa and mean OSI of 0.325 ± 0.025. In 3 aneurismal patients, jet flow impingement on the aortic wall resulted in large TAWSS values and low OSI which were amplified by the AI degree. However, the tissue strength did not appear to be significantly reduced. The fourth patient, which showed the lowest TAWSS due to the absence of jet flow, had the smallest strength in vitro. Interestingly this patient presented a bovine arch abnormality. Jet flow impingement with high WSS values is frequent in ATAAs and our methodology seems to be appropriate for determining whether it may increase the risk of rupture or not.

Perfusion computed tomography imaging of abdominal aortic aneurysms may be of value for patient specific rupture risk estimation.

Abdominal aortic aneurysm (AAA) continues to pose a significant cause of unexpected mortality in the developed countries with its incidence constantly rising. The indication of elective surgical repair is currently based on the maximum diameter and growth rate criteria which represent an oversimplification of the Law of Laplace stating that the stress exerted in a cylinder or sphere is proportional to its radius. These criteria fail to capture the complex pathophysiology of the aneurismal disease thus often leading to therapeutic inaccuracies (treating large AAAs with a very low actual rupture risk while observing smaller ones with a much greater risk). Aneurysmal disease is mainly a degenerative process leading to loss of structural integrity of the diseased aortic wall which cannot withhold the stresses due to systemic pressurization. Moreover aortic wall degeneration has been shown to be a localized phenomenon and rupture depends on the pointwise comparison of strength and stress rather than a global aortic wall weakening. Ex-vivo mechanical studies have related vessel wall hypoxia to loss of structural endurance and reduced wall strength. Therefore a module to capture in vivo variation of aortic wall blood supply and oxygenation would be of value for the evaluation of AAA rupture risk. Perfusion computed tomography (PCT) imaging represents a novel technique which has been already used to estimate tissue vascularity in several clinical conditions but not aneurismal disease. We hypothesize that PCT could be used as an adjunct tool during AAA diagnostics in order to evaluate aortic wall oxygenation in vivo, therefore providing a possible means to identify weak spots making the lesion amenable to rupture.

Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification.

Advancements in identifying biomechanical determinants for abdominal aortic aneurysm rupture.

Abdominal aortic aneurysms are a common health problem and currently the need for surgical intervention is determined based on maximum diameter and growth rate criteria. Since these universal variables often fail to predict accurately every abdominal aortic aneurysms evolution, there is a considerable effort in the literature for other markers to be identified towards individualized rupture risk estimations and growth rate predictions. To this effort, biomechanical tools have been extensively used since abdominal aortic aneurysm rupture is in fact a material failure of the diseased arterial wall to compensate the stress acting on it. The peak wall stress, the role of the unique geometry of every individual abdominal aortic aneurysm as well as the mechanical properties and the local strength of the degenerated aneurysmal wall, all confer to rupture risk. In this review article, the assessment of these variables through mechanical testing, advanced imaging and computational modeling is reviewed and the clinical perspective is discussed.

Novel seed protection in the recently evolved invasive, California wild radish, a hybrid Raphanus sp. (Brassicaceae).

UNLABELLED: • PREMISE OF THE STUDY: Interspecific hybridization may have considerable effects on plant structural defenses that can contribute to the success of invasive hybrid lineages. Changes in fruit structural and material properties are predicted to have key effects on predispersal granivory.• METHODS: Here, we asked whether plant structure can increase the fitness of a hybrid invasive relative to its progenitors. We compared fruit traits of the hybrid-derived lineage, California wild radish, with its progenitors, cultivated radish and jointed charlock.• KEY RESULTS: The hybrid lineage is significantly different from one or both ancestors in fruit length, mass, diameter, volume, shape, wall strength, and internal seed distribution. We experimentally exposed the fruits of both hybrid and wild progenitor to avian granivores and found (1) different types and degrees of damage at the different fruit sections and (2) significant differences in the inflicted damage at different sections of the fruit.• CONCLUSIONS: Combining our descriptive and experimental data, we conclude that the novel seed protection of the hybrid California wild radish is an important defense mechanism. It offers differential protection to its seeds and according to our findings, better protection of seeds that have been found to be better competitors. We suggest then that the fruit has enabled, at least in part, the successful replacement of the parental species by the hybrid lineage.

Preoperative anemia impacts early postoperative recovery following autologous breast reconstruction.

INTRODUCTION: Preoperative anemia impacts a significant portion of breast reconstruction patients, though this does not appear to affect surgical outcomes. The impact of anemia on postoperative physical and mental health, however, is unknown. This study aimed to prospectively evaluate the role of preoperative anemia in recovery after autologous reconstruction. METHODS: From 2005 to 2010, we prospectively assessed autologous breast reconstruction patients with satisfaction surveys, strength and functional tests, and the short form 36 (SF36). Data was collected preoperatively and at early (<90d), intermediate (90-365d), and late (>365d) follow-up. We stratified patients by presence or lack of preoperative anemia (hemoglobin<12 g/dL). RESULTS: Of 399 patients undergoing reconstruction, 179 enrolled in the study. Anemic patients (n = 31, 17%) had higher rates of preoperative chemotherapy (p = 0.02) and lower rates of radiation (p = 0.001). Preoperatively, anemic patients reported worse physical (p < 0.001), mental (p = 0.003) and overall health (p = 0.0003). These scores worsened postoperatively for anemic and nonanemic patients, though anemic patients had lower average scores in all SF36 categories. This was significant only for early follow-up physical health (p = 0.02). Change in SF36 scores and objective physical exam assessments did not differ between the two cohorts. CONCLUSIONS: Though preoperative anemia may not impact surgical outcomes, it adversely impacts the recovery of breast reconstruction patients. Subjective physical health differences were significant in early follow-up, though this did not translate to differences in mental health or satisfaction. We advocate for preoperative optimization of hemoglobin to enhance the early recovery potential of breast reconstruction patients.