Wall Stiffness Research Articles

Aldose Reductase and Protein Glycation Inhibitory Activity of Dark Chocolate-Assisted Zinc Oxide Nanoparticles.

Introduction One of the most common health issues that the global population is dealing with is the associated complications of diabetes, which encompasses cataracts, peripheral neuropathy, vascular damage, impaired wound healing, retinal issues, and arterial wall stiffening. The present study is aimed to evaluate the effect of dark chocolate and its assisted zinc oxide nanoparticles against diabetes-associated complications. Materials and methods Zinc oxide nanoparticles were synthesized using commercially dark chocolate (DC-ZnO NP). The synthesized DC-ZnO NPs were evaluated against recombinant aldose reductase (AR) activity and the formation of advanced glycation end products (AGEs). Aminoguanidine and gallic acid were used as reference standards for AGE assay and sorbitol accumulation inhibition, respectively. Results The results of the present study showed that green synthesized DC-ZnO NP had a significant dose-dependent inhibitory activity on both AR and AGEs. The inhibitory activity was compared to that of quercetin and aminoguanidine, respectively. Conclusion Targeting the endogenous antioxidant systems like AGEs and AR enzymes seems to provide a promising therapeutic approach, thus concluding that ZnO-NP could be a promising agent for treating diabetes-related complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy that provide grounds for further clinical investigations and trials.

Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening, and osteopontin release in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their role in AAA is poorly understood. The present study revealed that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the extracellular matrix (ECM). They are responsible for the up-regulation of SPP1 (osteopontin, OPN) gene expression in macrophages and aortic tissue, which triggers inflammation and remodelling and also platelet adhesion and migration into the abdominal aortic wall and the intraluminal thrombus (ILT). Further, enhanced platelet activation and pro-coagulant activity result in elevated gene expression of various cytokines, Mmp9 and Col1a1 in macrophages and Il-6 and Mmp9 in fibroblasts. Enhanced platelet activation and pro-coagulant activity were also detected in AAA patients. Further, we detected platelets and OPN in the vessel wall and in the ILT of patients who underwent open repair of AAA. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodelling, with reduced elastin fragmentation and aortic diameter expansion. Of note, OPN co-localized with platelets, suggesting a potential role of OPN for the recruitment of platelets into the ILT and the aortic wall. In conclusion, our data strongly support the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients.

Associations of Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology in Early Adolescence: A Prospective Population-Based Study.

Arterial wall thickness and stiffness, and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health-related brain changes may be observable already in adolescence. We examined whether (1) carotid intima-media thickness, (2) carotid distensibility, and (3) systolic blood pressure and diastolic blood pressure, measured at the age of 10 years, were associated with brain volumes and white matter microstructure (ie, fractional anisotropy and mean diffusivity) at the age of 14 years. In addition to cross-sectional analyses, we explored associations with longitudinal change in each brain outcome from 10 to 14 years. Analyses were based on 5341 children from the Generation R Study. Higher diastolic blood pressure was associated with lower total brain volume (β, -0.04 [95% CI, -0.07 to -0.01]) and gray matter volume (β, -0.04 [95% CI, -0.07 to -0.01]) at the age of 14 years, with stronger associations in higher diastolic blood pressure ranges. Similar associations emerged between systolic blood pressure and brain volumes, but these were no longer significant after adjusting for birth weight. No associations were observed between blood pressure and white matter microstructure or between carotid intima-media thickness or distensibility and brain morphology. Arterial blood pressure, but not intima-media thickness and distensibility, is associated with structural neuroimaging markers in early adolescence. Volumetric measures may be more sensitive to these early arterial health differences compared with microstructural properties of the white matter, but further studies are needed to confirm these results and assess potential causal mechanisms.

Foxo3a and cardiac myofibroblast transdifferentiation after myocardial infarction

Abstract Background Fibroblast/ myofibroblast differentiation following acute myocardial infarction (MI) is important for myocardial scar formation but also causes adverse remodeling and stiffening of the myocardium leading to cardiac dysfunction and heart failure. Transdifferentiation of myofibroblasts are characterized by periostin, and extracellular matrix protein expression. The transcription factor forkhead box O 3 (FOXO3a) has been recently shown to inhibit hypertrophic cardiac remodeling. Purpose We hypothesized that FOXO3a, a key regulator of cell size, immunity, and cell differentiation, might inhibit transdifferentiation of fibroblasts into myofibroblasts and therefore cardiac fibrosis after MI. Methods Acute MI was induced in Foxo3a-/- mice and wild-type littermates by permanent LAD ligation. Cardiac function was determined by transthoracic echocardiography (TTE) at baseline as well as on days 4 and 14 post-MI. Immune histochemistry was performed with collagen and periostin. Finally, fibroblast differentiation was investigated by single nucleus RNA-sequencing (snRNA-seq). Results Foxo3a-/- mice showed significantly improved survival despite similar infarct size post-MI (p<0.01). The survival advantage was in part due to reduced cardiac ruptures on autopsy. TTE showed reduced LV function, cardiac output, and global strain 4 days post-MI that did not differ between both groups of animals. However, systolic LV function was significantly attenuated in Foxo3a-/- mice 14 days post-MI indicating enhanced wall stiffness. In line with these findings, sn-RNAseq on day 4 post-MI revealed significantly increased numbers of periostin positive myofibroblasts (Myo) (p<0.05) important for stabilizing matrix interactions that transdifferentiated mainly from progenitor-like state fibroblasts (PLS) and homeostatic epicardial derived fibroblasts (HEpiD) in Foxo3a-/- mice. Myo differentially expressed, i.e. upregulated genes important for extracellular matrix structure and organization, cell migration and collagen organization. Moreover, an upregulation of pro-fibrotic genes was observed in other fibroblast clusters such as in HEpiD (i.e., Col1a1, Col1a2, Col3a1), PLS (i.e., fgf10, il1r1), late response fibroblasts (LR-F) (i.e., Col14a1, Rin2) and in activated fibroblasts (F-ACT) (i.e., Gpc6, Slt2) in Foxo3a-/- mice. These changes were corroborated by significantly elevated collagen type 1 and 3 as well as periostin protein expression in Foxo3a-/- mice. Cell chat analysis indicated enhanced number of interactions and interaction strength of myeloid cells with fibroblasts in Foxo3a-/- mice. Conclusion Our data identify Foxo3a as a master regulator of cardiac remodeling attenuating myofibroblast transdifferentiation after acute MI. These findings suggest that deficiency of Foxo3a promotes early scar formation preventing rupture but also contributes to adverse remodeling in later stages resulting in impaired cardiac function and enhanced fibrosis after MI.

Abstract 14407: Right Ventricular Myocardial Stiffening is Associated With Pulmonary Arterial Stiffening in Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) increases vascular resistance in the lung leading to remodeling of the proximal pulmonary artery (PA). PH also leads to the right ventricular (RV) remodeling following increased RV afterload. Studies of tissue remodeling in PH have focused on either the RV or PA, leaving the understanding of the RV-PA remodeling relationship elusive. We hypothesize that PA proximal tissue stiffening is associated with RV free wall (RVFW) stiffening. Methods: The mild model of PH was developed by placing SD rats (n=6) in a hypoxia chamber (10% O2) for 3 weeks, followed by one week of normoxia. The severe model of PH was developed by injecting one dose of SU5416 (20 mg/kg sc) into CDF rats (n=6) followed by the hypoxia protocol. Control rats (n=6 each for SD and CDF) were kept in normoxia at all times. Each group was half male and half female. RVFW and main PA tissues were harvested and characterized through mechanical tests. Tissue stiffness was calculated as the slope of the ensemble stress-strain curve (sum of circumferential and longitudinal stress) at a large strain (>30%) for the RVFW and PA specimens. Results: RVSP increased, and PAT decreased in both models. These changes were significant only in the severe model (Figs. 1A, B). Similarly, RVFW and PA stiffnesses increased significantly only in the severe model (Figs. 1C, D). A significant positive correlation between RVFW and PA stiffness was observed (R2 = 0.59, p=0.0001, Fig. 1E). Conclusions. Our results demonstrate, for the first time, a significant correlation between RVFW and PA stiffening in PH. Proximal PA stiffening changes the pulsatile component of the RV afterload, contributing to the RVFW stiffening, which is known to be a key precursor of RV failure. Our results suggest that the proximal PA stiffening may worsen RV stiffening independent of increases in PA distal resistance. Further studies are needed to determine the role of resistive vs. pulsatile RV afterload in the outcome of RV remodeling.

Machine learning modeling of lung mechanics: Assessing the variability and propagation of uncertainty in respiratory-system compliance and airway resistance

Background and ObjectiveTraditional assessment of patient response in mechanical ventilation relies on respiratory-system compliance and airway resistance. Clinical evidence has shown high variability in these parameters, highlighting the difficulty of predicting them before the start of ventilation therapy. This motivates the creation of computational models that can connect structural and tissue features with lung mechanics. In this work, we leverage machine learning (ML) techniques to construct predictive lung function models informed by non-linear finite element simulations, and use them to investigate the propagation of uncertainty in the lung mechanical response. MethodsWe revisit a continuum poromechanical formulation of the lungs suitable for determining patient response. Based on this framework, we create high-fidelity finite element models of human lungs from medical images. We also develop a low-fidelity model based on an idealized sphere geometry. We then use these models to train and validate three ML architectures: single-fidelity and multi-fidelity Gaussian process regression, and artificial neural networks. We use the best predictive ML model to further study the sensitivity of lung response to variations in tissue structural parameters and boundary conditions via sensitivity analysis and forward uncertainty quantification. Codes are available for download at https://github.com/comp-medicine-uc/ML-lung-mechanics-UQ ResultsThe low-fidelity model delivers a lung response very close to that predicted by high-fidelity simulations and at a fraction of the computational time. Regarding the trained ML models, the multi-fidelity GP model consistently delivers better accuracy than the single-fidelity GP and neural network models in estimating respiratory-system compliance and resistance (R2∼0.99). In terms of computational efficiency, our ML model delivers a massive speed-up of ∼970,000× with respect to high-fidelity simulations. Regarding lung function, we observed an almost matched and non-linear behavior between specific structural parameters and chest wall stiffness with compliance. Also, we observed a strong modulation of airways resistance with tissue permeability. ConclusionsOur findings unveil the relevance of specific lung tissue parameters and boundary conditions in the respiratory-system response. Furthermore, we highlight the advantages of adopting a multi-fidelity ML approach that combines data from different levels to yield accurate and efficient estimates of clinical mechanical markers. We envision that the methods presented here can open the way to the development of predictive ML models of the lung response that can inform clinical decisions.

Effectiveness of a fixed combination of amlodipine/indapamide in hypertensive patients in real clinical practice

Objective. To assess the possibility of obtaining and the degree of additional antihypertensive effect, the dynamics of vascular wall stiffness parameters, vascular age indicators in patients with uncontrolled hypertension (HTN) when transferring from previous therapy to a fixed combination of amlodipine/indapamide in typical outpatient practice.Design and methods. Twenty-five patients with 1–3 degree HTN who got a prescription of a fixed combination of amlodipine/indapamide (ARIFAM 5/1,5 or 10/1,5 mg, Servier) were included in the study. The follow-up duration was 2 months and included the following methods: clinical assessment (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate), with titration of the drug dose every two weeks; double assessment (at the beginning and at the end of the study) of arterial stiffness based on the determination of the cardio-ankle vascular index (CAVI), biological age of vessels using the VaSeraVS‑1500N volumetric sphygmography device, as well as quality of life indicators (SF‑36 questionnaire). The reliability of changes in the studied parameters during active outpatient management of patients was assessed.Results. Combined pharmacotherapy using a fixed combination of amlodipine/indapamide was well tolerated by all patients. We recorded a significant decrease in SBP on average by 31,0 ± 10,6 mmHg, DBP by 11,0 [7,0; 20,0] mmHg, and the achievement of the target SBP level at the end of the 2nd month was shown in 17 (68 %) patients, the target DBP level was found in 100 % of patients. A significant decrease in vascular wall stiffness parameters was shown as a decrease in the CAVI index (p = 0,034), a decrease in AI (p = 0,0001) and the PEP/ET ratio of the Veissler coefficient (p = 0,009), as well as in the calculated vascular age indicator (p = 0,00001). Significant (p = 0,0001) changes were recorded for most data of quality of life (SF‑36) in patients with HTN, with the exception of the social functioning scale.Conclusions. Combined pharmacotherapy of patients with 1–3 degree HTN with the inclusion of a fixed combination drug amlodipine/indapamide with prolonged release has a clear positive effect, i. e. improved hemodynamic parameters, a significant reduction in vascular stiffness, a decrease in vascular age and improved quality of life.

Correlation between plant cell wall stiffening and root extension arrest phenotype in the combined abiotic stress of Fe and Al.

The plasticity and growth of plant cell walls (CWs) remain poorly understood at the molecular level. In this work, we used atomic force microscopy (AFM) to observe elastic responses of the root transition zone of 4-day-old Arabidopsis thaliana wild-type and almt1-mutant seedlings grown under Fe or Al stresses. Elastic parameters were deduced from force-distance curve measurements using the trimechanic-3PCS framework. The presence of single metal species Fe2+ or Al3+ at 10 µM exerts no noticeable effect on the root growth compared with the control conditions. On the contrary, a mix of both the metal ions produced a strong root-extension arrest concomitant with significant increase of CW stiffness. Raising the concentration of either Fe2+ or Al3+ to 20 µM, no root-extension arrest was observed; nevertheless, an increase in root stiffness occurred. In the presence of both the metal ions at 10 µM, root-extension arrest was not observed in the almt1 mutant, which substantially abolishes the ability to exude malate. Our results indicate that the combination of Fe2+ and Al3+ with exuded malate is crucial for both CW stiffening and root-extension arrest. However, stiffness increase induced by single Fe2+ or Al3+ is not sufficient for arresting root growth in our experimental conditions.

Study of indicators of arterial stiffness in young people depending on ‘classical’ and ‘modern’ risk factors

Objective. To identify ‘classical’ and ‘modern’ risk factors (RFs) in young people aged 18–25 years in a student environment and evaluate their impact on arterial wall stiffness using non-invasive examination methods.Materials and methods. 171 students of a humanitarian university aged 18–25 years old were examined, of which 52.1 % were girls and 47.9 % were boys. An anonymous survey was conducted to identify the main risk factors. The method of volumetric sphygmography and highly sensitive compression oscillometry was used to assess the state of the vascular wall.Results. Against the background of ‘classic’ risk factors (low physical activity – 61.9 %, essential arterial hypertension [AH] – 29.8 %, aggravated heredity for hypertension – 18.3 %, overweight – 14.0 %, obesity – 8.5 %, cigarette smoking – 3.0 %), ‘modern’ RFs were identified: a combination of hookah and cigarette smoking – 31.0 %, use of electronic cigarettes – 17.0 %, use of energy drinks – 25.3 %. In students with the presence of ‘modern’ PR, the values of pulse wave velocity (PWV) were obtained – 8.4 ± 2.7 m/s, relative to the PWV of students without PR 5.1 ± 0.6 m/s (p = 0.002). It was found that the relative risk of an increase in PWV with the combined use of hookah and cigarettes increases by 52.1 times (95 % CI: 11.2–242.1 at χ2 = 37.987; p = 0.001), with the use of energy drinks by 27.4 times (95 % CI: 6.8–111.0 at χ2 = 29.328; p = 0.001), when using electronic cigarettes by 2.6 times (95 % CI: 1.3–5.2 at χ2 = 6.496; p = 0.011).Conclusions. Students aged 18–25 years showed a high adherence to modern risk factors (a combination of hookah and cigarette smoking, energy drinks, use of electronic cigarettes) that lead to a violation of the elastic properties of the vascular wall, which indicates endothelial dysfunction.

Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid-femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction P>0.05). However, the CFPWV-peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular-pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community-dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.

Investigation on tearing damage of CFRP circular cell honeycomb in end-face grinding

CFRP circular cell honeycomb has promising applications in the aerospace field due to its excellent mechanical properties. However, a large number of periodically distributed tearing damages severely restrict the high-quality machining of CFRP circular cell honeycomb. This paper investigates the formation mechanism of tearing damages during end-face grinding of CFRP circular cell honeycomb and proposes suppression strategies. In this paper, a maximum undeformed chip thickness model considering tearing damage distribution is developed, and the evolution behavior of tearing damage is studied by combining the material removal process and grinding force. The grinding force and maximum tearing damage depth in different grinding conditions are analyzed. The results show that the formation of tearing damage in the cut-in stage is related to the weak stiffness of thin walls and the radial grinding force. The radial grinding force and maximum tearing depth can be altered by changing the maximum undeformed chip thickness which can be adjusted for different grinding speeds, feed rates, and offset ratios. The low-damage machining of CFRP circular cell honeycomb can be achieved by using a large offset ratio and variable feed rate.

Vascular deficits contributing to skeletal fragility in type 1 diabetes.

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.

Effect of stenotic shapes and arterial wall elasticity on the hemodynamics

The present study employs an arbitrary Lagrangian–Eulerian fluid–structure interaction approach to investigate pulsatile blood flow through a deformable stenosed channel. The flow is modeled by solving the incompressible continuity and momentum equations using finite element-based commercial solver COMSOL Multiphysics®. In this work, we explore the effects of different stenotic shapes—elliptical, round, and sinusoidal, degrees of stenosis (30%, 50%, and 70%), and arterial wall stiffnesses—0.5, 1.5, and 2.5 MPa on the velocity profile, pressure and wall shear stress distribution, and wall deformation. The oscillatory shear index (OSI) is analyzed to predict further plaque formation in the stenosed artery. We find that the flow velocity, wall shear stress, and pressure difference across the stenosed region increase with an increase in the stenotic severity and artery stiffness. The velocity profiles intersect at a radial location in the stenotic region termed critical radius, where relative magnitudes get reversed. With the increase in stenotic severity, the wall displacement decreases at the throat and increases at the upstream side. With the increase in wall stiffness, the wall deformation decreases, and shear stress increases, thereby increasing the pressure drop across the stenosed region. At a lower mass flow rate and a higher degree of stenosis, the vortices are formed upstream and downstream of the stenosed region for all stenotic shapes. The vorticity magnitude is found to be more than 21% higher for sinusoidal stenotic shape than round and elliptical ones. The effect of stenotic profile on the pressure drop characteristics shows that blood experiences maximum wall shear stress for the sinusoidal stenotic geometry, whereas the pressure drop is the maximum for the elliptical stenotic shape. The elliptical stenotic shape is more prone to further plaque formation than round and sinusoidal stenotic shapes. At lower Womersley number (Wo=2.76) corresponding to 60 beats per min heart beat rate, secondary vortices are formed downstream of the channel, causing higher OSI.

Regional and Global Aortic Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is commonly defined as a localised dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA. Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with AAA > 30 mm (range 36 - 70 mm, all male, age range 65 - 76 years) and 27 age- and sex-matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured. Global aortic PWV was greater in men with AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls. PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.

Investigating Balloon-Vessel Contact Pressure Patterns in Angioplasty: In Silico Insights for Drug-Coated Balloons

Drug-Coated Balloons have shown promising results as a minimally invasive approach to treat stenotic arteries, but recent animal studies have revealed limited, non-uniform coating transfer onto the arterial lumen. In vitro data suggested that local coating transfer tracks the local Contact Pressure (CP) between the balloon and the endothelium. Therefore, this work aimed to investigate in silico how different interventional and device parameters may affect the spatial distribution of CP during the inflation of an angioplasty balloon within idealized vessels that resemble healthy femoral arteries in size and compliance. An angioplasty balloon computational model was developed, considering longitudinal non-uniform wall thickness, due to its forming process, and the folding procedure of the balloon. To identify the conditions leading to non-uniform CP, sensitivity finite element analyses were performed comparing different values for balloon working length, longitudinally varying wall thickness, friction coefficient on the balloon-vessel interface, vessel wall stiffness and thickness, and balloon-to-vessel diameter ratio. Findings indicate a significant irregularity of contact between the balloon and the vessel, mainly affected by the balloon’s unfolding and longitudinal thickness variation. Mirroring published data on coating transfer distribution in animal studies, the interfacial CP distribution was maximal at the middle of the balloon treatment site, while exhibiting a circumferential pattern of linear peaks as a consequence of the particular balloon-vessel interaction during unfolding. A high ratio of balloon-to-vessel diameter, higher vessel stiffness, and thickness was found to increase significantly the amplitude and spatial distribution of the CP, while a higher friction coefficient at the balloon-to-vessel interface further exacerbated the non-uniformity of CP. Evaluation of balloon design effects revealed that the thicker tapered part caused CP reduction in the areas that interacted with the extremities of the balloon, whereas total length only weakly impacted the CP. Taken together, this study offers a deeper understanding of the factors influencing the irregularity of balloon-tissue contact, a key step toward uniformity in drug-coating transfer and potential clinical effectiveness.

Comparative characteristics of patients with arterial hypertension with positive and negative reactions to salt load at night time

Objective: comparison of peripheral and central blood pressure, vascular wall stiffness and glomerular filtration rate in patients divided into salt-sensitive and salt-resistant based on the dynamics of blood pressure during night time after salt loading.Materials and methods: the study included 180 patients with arterial hypertension: 96 men (53%) and 84 (47%) women, median age 59 (56-64) years. Salt sensitivity was assessed according to the method of V.I. Kharchenko with distribution into groups according to the results of blood pressure dynamics at night. Peripheral and central blood pressure, vascular stiffness, and glomerular filtration rate were compared.Results: in 61% of salt resistant patients, there was a sufficient decrease in blood pressure during nocturnal sleep — the “dipper” profile, while in the group of salt sensitive patients, the decrease in blood pressure was sufficient only in 48%. Glomerular filtration rate was also higher in salt resistant patients compared to salt sensitive: 76,5 ml/min./1.73m2 versus 68 ml/min./1,73m2.Conclusion: arterial hypertension is more severe in salt sensitive patients, which was reflected in the intergroup comparison of peripheral and central blood pressure, vascular stiffness, and excretory function of the kidneys. Assessment of salt sensitivity at night may be useful in identifying high-risk groups of patients requiring the most careful monitoring and “aggressive” antihypertensive therapy.

Seismic behavior of reinforced concrete slender walls subjected to variable axial loads

Reinforced concrete (RC) shear walls are the major lateral load-carrying structural components in high-rise buildings. Under strong earthquake motions, the axial loads of RC walls are not constant axial compression, but may be in tension, resulting in the axial load of RC walls varying from compression to tension. In this study, three RC slender wall specimens (shear-to-span ratio λ = 2.0) were tested to study the effect of the fluctuating range and loading patterns of variable axial forces on their cyclic behavior, including failure modes, hysteretic response, strength and deformation capacity. Test results indicated that the final failure of RC slender walls subjected to variable axial forces was controlled by flexural failure in the compressive-flexural direction. The hysteretic curves of RC slender walls were asymmetric and substantively different from the hysteretic curves of RC slender walls with constant axial loads. The fluctuating range of axial forces had a limited influence on the shape of hysteretic curves, while the loading patterns significantly changed the shape of these hysteretic curves. Under the variable axial forces, the lateral strength and deformation capacity of RC slender walls depended on the fluctuating range of axial forces, while loading patterns had limited influence when the fluctuating range of axial forces kept constant. The loading patterns had a limited influence on the lateral stiffness of RC slender walls, while the increase of fluctuating range of axial forces increased the difference between compressive-flexural and tensile-flexural lateral stiffness. No matter in tensile-flexural or compressive-flexural directions, the assumption that the wall section remains plane after deformation is suitable for RC slender walls under the variable axial forces, and enables reasonable estimations of yielding and peak strength. Finally, a finite element model was developed for predicting the cyclic behavior of RC walls under the variable axial loads.

The SYP123-VAMP727 SNARE complex delivers secondary cell wall components for root hair shank hardening in Arabidopsis.

The extended tubular shape of root hairs is established by tip growth and concomitant hardening. Here, we demonstrate that a syntaxin of plants (SYP)123-vesicle-associated membrane protein (VAMP)727-dependent secretion system delivers secondary cell wall components for hardening the subapical zone and shank of Arabidopsis (Arabidopsis thaliana) root hairs. We found increased SYP123 localization at the plasma membrane (PM) of the subapical and shank zones compared with the tip region in elongating root hairs. Inhibition of phosphatidylinositol (PtdIns)(3,5)P2 production impaired SYP123 localization at the PM and SYP123-mediated root hair shank hardening. Moreover, root hair elongation in the syp123 mutant was insensitive to a PtdIns(3,5)P2 synthesis inhibitor. SYP123 interacts with both VAMP721 and VAMP727. syp123 and vamp727 mutants exhibited reduced shank cell wall stiffness due to impaired secondary cell wall component deposition. Based on these results, we conclude that SYP123 is involved in VAMP721-mediated conventional secretion for root hair elongation as well as in VAMP727-mediated secretory functions for the delivery of secondary cell wall components to maintain root hair tubular morphology.

Numerical Modeling and Parametric Assessment of Log Shear Walls with Bonded Corners

ABSTRACT The paper investigates the stiffness and strength of log walls with standard and dovetail bonded corners under lateral loads. The finite element model is developed and validated with experimental work at small-scale and wall-scale levels. The validated wall-scale model was modified by conducting a detailed investigation on assessing the wall behaviour with varying crucial parameters, including coefficient of friction, vertical load, geometric irregularities, and the wall’s aspect ratio. The study suggested various techniques for improving the wall’s lateral load resistance capacities and initial stiffness, employing steel and wood pins.

Investigating the influence of plant fiber geometry on apparent transverse elastic properties through finite element analysis

This study explores the link between plant fiber geometry and its transverse behavior, focusing on the resulting apparent transverse stiffness as determined by analytical models. Using Finite Element Analysis (FEA) plant fiber transverse compression is simulated with two-dimensional models. Simplified geometric representations of common geometric features are examined, showing how distinct attributes influence behavior. The fiber lumen is shown to decrease apparent stiffness, while elliptical geometry and flat sections increase it. An adaptation of analytical models for elliptical cross-sections yields a 93 % improvement on identification accuracy. Furthermore, the transverse compression of realistic geometries, extracted from microscopy images and presenting a blend of different features, is simulated. The lumen’s impact on apparent stiffness is shown to outweigh the effects of other features. These findings show the importance of apparent stiffness over fiber cell wall stiffness and how it may evolve under repeated loading, which has important implications for the composites sector.