The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS.

BACKGROUND: PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS. METHODS: Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected. RESULTS: A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O). CONCLUSIONS: Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

On simulations of 3D fractional WBBM model through mathematical and graphical analysis with the assists of fractionality and unrestricted parameters.

This study retrieves some novel exact solutions to the family of 3D space-time fractional Wazwaz-Benjamin-Bona-Mahony (WBBM) equations in the context of diverse nonlinear physical phenomena resulting from water wave mechanics. The family of WBBM equations is transformed for this purpose using a space and time fractional transformation into an ordinary differential equation (ODE). The ODE then uses a strong method, namely the Unified Method. Consequently, lump solutions, dark-bright soliton, singular and multiple soliton solutions, and periodic solutions are investigated. The disparities between the current study's conclusions and previously acquired solutions via other approaches are examined. All wave solutions produced are determined to be novel in terms of fractionality, unrestricted parameters, and implemented technique sense. The impact of unrestricted parameters and fractionality on the obtained solutions are visually presented, along with physical explanations. It is observed that the wave portents are varied with the increase of unrestricted parameters as well as fractionality. We dynamically showed that the appropriate transformation and the applied Unified approach more proficient in the study of water wave dynamics and might be used in future researches to clarify the many physical phenomena. The novelty of this work validate that the proposed method seem simple and useful tools for obtaining the solutions in PDEs and it is expected to use in mathematical physics and optical engineering.

Computing the influence of lipids and lipid complexes on membrane mechanics.

Methodology for extracting the spontaneous curvature, bending modulus, and neutral surface of a lipid bilayer is described. The "SPEX" method is a robust technique for computing the bilayer bending modulus while allowing for resolution of the spontaneous curvature of specific interacting lipids and complexes, and the dependence of spontaneous curvature on wavelength. The method is described referring to the publicly available MembraneAnalysis.jl software package.

Modeling the mechanochemical feedback for membrane-protein interactions using a continuum mesh model.

The Helfrich free energy is widely used to model the generation of membrane curvature due to different physical and chemical components. The governing equations resulting from the energy minimization procedure are a system of coupled higher order partial differential equations. Simulations of membrane deformation for obtaining quantitative comparisons against experimental observations require computational schemes that will allow us to solve these equations without restrictions to axisymmetric coordinates. Here, we describe one such tool that we developed in our group based on discrete differential geometry to solve these equations along with examples.

Effects of nursing team communication and collaboration on treatment outcomes in intensive care unit patients with severe pneumonia.

BACKGROUND: Severe pneumonia is a common severe respiratory infection worldwide, and its treatment is challenging, especially for patients in the intensive care unit (ICU). AIM: To explore the effect of communication and collaboration between nursing teams on the treatment outcomes of patients with severe pneumonia in ICU. METHODS: We retrospectively analyzed 60 patients with severe pneumonia who were treated at the ICU of the hospital between January 1, 2021 and December 31, 2023. We compared and analyzed the respiratory mechanical indexes [airway resistance (Raw), mean airway pressure (mPaw), peak pressure (PIP)], blood gas analysis indexes (arterial oxygen saturation, arterial oxygen partial pressure, and oxygenation index), and serum inflammatory factor levels [C-reactive protein (CRP), procalcitonin (PCT), cortisol (COR), and high mobility group protein B1 (HMGB1)] of all patients before and after treatment. RESULTS: Before treatment, there was no significant difference in respiratory mechanics index and blood gas analysis index between 2 groups (P > 0.05). However, after treatment, the respiratory mechanical indexes of patients in both groups were significantly improved, and the improvement of Raw, mPaw, plateau pressure, PIP and other indexes in the combined group after communication and collaboration with the nursing team was significantly better than that in the single care group (P < 0.05). The serum CRP and PCT levels of patients were significantly decreased, and the difference was statistically significant compared with that of nursing group alone (P < 0.05). The levels of serum COR and HMGB1 before and after treatment were also significantly decreased between the two groups. CONCLUSION: The communication and collaboration of the nursing team have a significant positive impact on respiratory mechanics indicators, blood gas analysis indicators and serum inflammatory factor levels in the treatment of severe pneumonia patients in ICU.

A mechanics theory for the exploration of a high-throughput, sterile 3D in vitro traumatic brain injury model.

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several in vitro and in vivo models for traumatic brain injury (TBI) continue to be developed for delineating the various complex pathophysiological processes involved in its onset and progression. Developing an in vitro TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of in vivo brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids are a key requirement in any effective in vitro TBI model. The spheroids' shape and size, however, make mechanically loading them, especially in a high-throughput, sterile, and reproducible manner, quite challenging. To address this challenge, we present an idea for a spheroid-based, in vitro TBI model in which the spheroids are mechanically loaded by being spun by a centrifuge. (An experimental demonstration of this new idea will be published shortly elsewhere.) An issue that can limit its utility and scope is that imaging techniques used in 2D and 3D in vitro TBI models cannot be readily applied in it to determine spheroid strains. In order to address this issue, we developed a continuum mechanics-based theory to estimate the spheroids' strains when they are being spun at a constant angular velocity. The mechanics theory, while applicable here to a special case of the centrifuge-based TBI model, is also of general value since it can help with the further exploration and development of TBI models.

Size Matters: Rethinking Hertz Model Interpretation for Cell Mechanics Using AFM.

Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young's modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young's modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

Cryptic Extensibility in von Willebrand Factor Revealed by Molecular Nanodissection.

Von Willebrand factor (VWF) is a multimer with a variable number of protomers, each of which is a head-to-head dimer of two multi-domain monomers. VWF responds to shear through the unfolding and extension of distinct domains, thereby mediating platelet adhesion and aggregation to the injured blood vessel wall. VWF's C1-6 segment uncoils and then the A2 domain unfolds and extends in a hierarchical and sequential manner. However, it is unclear whether there is any reservoir of further extensibility. Here, we explored the presence of cryptic extensibility in VWF by nanodissecting individual, pre-stretched multimers with atomic force microscopy (AFM). The AFM cantilever tip was pressed into the surface and moved in a direction perpendicular to the VWF axis. It was possible to pull out protein loops from VWF, which resulted in a mean contour length gain of 217 nm. In some cases, the loop became cleaved, and a gap was present along the contour. Frequently, small nodules appeared in the loops, indicating that parts of the nanodissected VWF segment remained folded. After analyzing the nodal structure, we conclude that the cryptic extensibility lies within the C1-6 and A1-3 regions. Cryptic extensibility may play a role in maintaining VWF's functionality in extreme shear conditions.

Computational Approach for the Development of pH-Selective PD-1/PD-L1 Signaling Pathway Inhibition in Fight with Cancer.

Immunotherapy, particularly targeting the PD-1/PD-L1 pathway, holds promise in cancer treatment by regulating the immune response and preventing cancer cells from evading immune destruction. Nonetheless, this approach poses a risk of unwanted immune system activation against healthy cells. To minimize this risk, our study proposes a strategy based on selective targeting of the PD-L1 pathway within the acidic microenvironment of tumors. We employed in silico methods, such as virtual screening, molecular mechanics, and molecular dynamics simulations, analyzing approximately 10,000 natural compounds from the MolPort database to find potential hits with the desired properties. The simulations were conducted under two pH conditions (pH = 7.4 and 5.5) to mimic the environments of healthy and cancerous cells. The compound MolPort-001-742-690 emerged as a promising pH-selective inhibitor, showing a significant affinity for PD-L1 in acidic conditions and lower toxicity compared to known inhibitors like BMS-202 and LP23. A detailed 1000 ns molecular dynamics simulation confirmed the stability of the inhibitor-PD-L1 complex under acidic conditions. This research highlights the potential of using in silico techniques to discover novel pH-selective inhibitors, which, after experimental validation, may enhance the precision and reduce the toxicity of immunotherapies, offering a transformative approach to cancer treatment.

What is the physical origin of the gradient flow structure of variational fracture models?

We investigate a physical characterization of the gradient flow structure of variational fracture models for brittle materials: a Griffith-type fracture model and an irreversible fracture phase field model. We derive the Griffith-type fracture model by assuming that the fracture energy in Griffith's theory is an increasing function of the crack tip velocity. Such a velocity dependence of the fracture energy is typically observed in polymers. We also prove an energy dissipation identity of the Griffith-type fracture model, in other words, its gradient flow structure. On the other hand, the irreversible fracture phase field model is derived as a unidirectional gradient flow of a regularized total energy. We have considered the time relaxation parameter a mathematical approximation parameter, which we should choose as small as possible. In this research, however, we reveal the physical origin of the gradient flow structure of the fracture phase field model (F-PFM) and show that the small time relaxation parameter is characterized as the rate of velocity dependence of the fracture energy. It is verified by comparing the energy dissipation properties of those two models and by analysing a travelling wave solution of the irreversible F-PFM. This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

Minimization of peak stresses with the shape derivative.

This article is concerned with the minimization of peak stresses occurring in linear elasticity. We propose to minimize the maximal von Mises stress of the elastic body. This leads to a non-smooth shape functional. We derive the shape derivative and associate it with the Clarke sub-differential. Using a steepest descent algorithm, we present numerical simulations. We compare our results to the usual [Formula: see text]-norm regularization and show that our algorithm performs better in the presented tests.This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

The Role of Hydrogen Bonding in the Raman Spectral Signals of Caffeine in Aqueous Solution.

The identification and quantification of caffeine is a common need in the food and pharmaceutical industries and lately also in the field of environmental science. For that purpose, Raman spectroscopy has been used as an analytical technique, but the interpretation of the spectra requires reliable and accurate computational protocols, especially as regards the Resonance Raman (RR) variant. Herein, caffeine solutions are sampled using Molecular Dynamics simulations. Upon quantification of the strength of the non-covalent intermolecular interactions such as hydrogen bonding between caffeine and water, UV-Vis, Raman, and RR spectra are computed. The results provide general insights into the hydrogen bonding role in mediating the Raman spectral signals of caffeine in aqueous solution. Also, by analyzing the dependence of RR enhancement on the absorption spectrum of caffeine, it is proposed that the sensitivity of the RR technique could be exploited at excitation wavelengths moderately far from 266 nm, yet achieving very low detection limits in the quantification caffeine content.

Engineering the Cellular Microenvironment: Integrating Three-Dimensional Nontopographical and Two-Dimensional Biochemical Cues for Precise Control of Cellular Behavior.

The development of biomaterials capable of regulating cellular processes and guiding cell fate decisions has broad implications in tissue engineering, regenerative medicine, and cell-based assays for drug development and disease modeling. Recent studies have shown that three-dimensional (3D) nanoscale physical cues such as nanotopography can modulate various cellular processes like adhesion and endocytosis by inducing nanoscale curvature on the plasma and nuclear membranes. Two-dimensional (2D) biochemical cues such as protein micropatterns can also regulate cell function and fate by controlling cellular geometries. Development of biomaterials with precise control over nanoscale physical and biochemical cues can significantly influence programming cell function and fate. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate the precise engineering of single cell architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between the nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, our results suggest that cell elongation on nanopillars enhances nanopillar-induced endocytosis. We believe our platform serves as a versatile tool for further explorations into programming cell function and fate through combined physical cues that create nanoscale curvature on cell membranes and biochemical cues that control the geometry of the cell.

Mechanical deformation and death of circulating tumor cells in the bloodstream.

The circulation of tumor cells through the bloodstream is a significant step in tumor metastasis. To better understand the metastatic process, circulating tumor cell (CTC) survival in the circulation must be explored. While immune interactions with CTCs in recent decades have been examined, research has yet to sufficiently explain some CTC behaviors in blood flow. Studies related to CTC mechanical responses in the bloodstream have recently been conducted to further study conditions under which CTCs might die. While experimental methods can assess the mechanical properties and death of CTCs, increasingly sophisticated computational models are being built to simulate the blood flow and CTC mechanical deformation under fluid shear stresses (FSS) in the bloodstream.Several factors contribute to the mechanical deformation and death of CTCs as they circulate. While FSS can damage CTC structure, diverse interactions between CTCs and blood components may either promote or hinder the next metastatic step-extravasation at a remote site. Overall understanding of how these factors influence the deformation and death of CTCs could serve as a basis for future experiments and simulations, enabling researchers to predict CTC death more accurately. Ultimately, these efforts can lead to improved metastasis-specific therapeutics and diagnostics specific in the future.

Biomechanical and Biochemical Changes in Murine Skin During Development and Aging.

Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower stiffening behavior at large force values and lower tensile strength. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. STATEMENT OF SIGNIFICANCE: Skin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment.

HepG2 cells undergo regulatory volume decrease by mechanically induced efflux of water and solutes.

This study challenges the conventional belief that animal cell membranes lack a significant hydrostatic gradient, particularly under anisotonic conditions, as demonstrated in the human hepatoma cell line HepG2. The Boyle van't Hoff (BvH) relation describes volumetric equilibration to anisotonic conditions for many cells. However, the BvH relation is simple and does not include many cellular components such as the cytoskeleton and actin cortex, mechanosensitive channels, and ion pumps. Here we present alternative models that account for mechanical resistance to volumetric expansion, solute leakage, and active ion pumping. We found the BvH relation works well to describe hypertonic volume equilibration but not hypotonic volume equilibration. After anisotonic exposure and return isotonic conditions cell volumes were smaller than their initial isotonic volume, indicating solutes had leaked out of the cell during swelling. Finally, we observed HepG2 cells undergo regulatory volume decrease at both 20 °C and 4 °C, indicating regulatory volume decrease to be a relatively passive phenomenon and not driven by ion pumps. We determined the turgor-leak model, which accounts for mechanical resistance and solute leakage, best fits the observations found in the suite of experiments performed, while other models were rejected.

Analysis of size effect and its influencing factors of brittle red sandstone with different heights.

We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications.

Proteolysis and Contractility Regulate Tissue Opening and Wound Healing by Lung Fibroblasts in 3D Microenvironments.

Damage and repair are recurring processes in tissues, with fibroblasts playing key roles by remodeling extracellular matrices (ECM) through protein synthesis, proteolysis, and cell contractility. Dysregulation of fibroblasts can lead to fibrosis and tissue damage, as seen in idiopathic pulmonary fibrosis (IPF). In advanced IPF, tissue damage manifests as honeycombing, or voids in the lungs. This study explores how transforming growth factor-beta (TGF-ß), a crucial factor in IPF, induces lung fibroblast spheroids to create voids in reconstituted collagen through proteolysis and cell contractility, a process is termed as hole formation. These voids reduce when proteases are blocked. Spheroids mimic fibroblast foci observed in IPF. Results indicate that cell contractility mediates tissue opening by stretching fractures in the collagen meshwork. Matrix metalloproteinases (MMPs), including MMP1 and MT1-MMP, are essential for hole formation, with invadopodia playing a significant role. Blocking MMPs reduces hole size and promotes wound healing. This study shows how TGF-ß induces excessive tissue destruction and how blocking proteolysis can reverse damage, offering insights into IPF pathology and potential therapeutic interventions.

Quantum inspired approach for denoising with application to medical imaging.

Background noise in many fields such as medical imaging poses significant challenges for accurate diagnosis, prompting the development of denoising algorithms. Traditional methodologies, however, often struggle to address the complexities of noisy environments in high dimensional imaging systems. This paper introduces a novel quantum-inspired approach for image denoising, drawing upon principles of quantum and condensed matter physics. Our approach views medical images as amorphous structures akin to those found in condensed matter physics and we propose an algorithm that incorporates the concept of mode resolved localization directly into the denoising process. Notably, our approach eliminates the need for hyperparameter tuning. The proposed method is a standalone algorithm with minimal manual intervention, demonstrating its potential to use quantum-based techniques in classical signal denoising. Through numerical validation, we showcase the effectiveness of our approach in addressing noise-related challenges in imaging and especially medical imaging, underscoring its relevance for possible quantum computing applications.

Early effect of different bifurcation techniques on left ventricular mechanics in elective percutaneous coronary intervention.

BACKGROUND: Bifurcation lesions are prevalent amongst patients with symptomatic coronary artery disease subjected to percutaneous coronary intervention (PCI). Recent consensus commends a conservative (provisional) approach when managing the side branch. Here, the aim was to explore the immediate impact of different bifurcation techniques (one stent and two stent strategies) on left ventricular LV) myocardial functions using speckle tracking echocardiography in patients subjected to elective PCI. Sixty two consecutive patients diagnosed with coronary bifurcation lesion (CBL) were enrolled. Patients were categorized into: one-stent strategy (Provisional group, n = 44) and a two-stent strategy (TAP, DK crush, or Culotte technique, n = 18), based on the coronary bifurcation site, angle, side branch diameter and Medina classification. LVEF%, regional and global longitudinal strain (GLS), and E/E' were measured before and within 24 h post PCI. RESULTS: In both provisional and 2- stent technique, the mitral inflow velocities and mitral annular velocities showed improvement with significant reduction in E/e' (P < 0.03 and P < 0.001) respectively while LVEF% did not change. There were no significant changes in any other echo parameters post PCI. In provisional group, there were significant improvements in LAD (P < 0.001), RCA (P < 0.01) territories and GLS (P < 0.01). Δ LAD was expressively higher (34.5%) compared with Δ LCX (9.6%) and ΔRCA (25.4%), P < 0.001, P < 0.01 respectively. In the 2-stent technique group, there were significant improvements in peak longitudinal strain of LAD territory (P < 0.01), RCA territory (P < 0.01) and GLS (P < 0.01) respectively. Δ LAD territory was significantly higher in provisional group in comparison with the 2- stent technique group. Δ GLS was correlated inversely to Gensini score in provisional group and to the number of vessel diseased in 2-stent technique group. CONCLUSION: PCI of the bifurcation lesion positively impact myocardial function. Both bifurcation techniques improve LV mechanical properties using 2D strain imaging while LV EF% remains unchanged.