Mechanical Behavior of Hybrid Thin Films Fabricated by Sequential Infiltration Synthesis in Water-Rich Environment.

Sequential infiltration synthesis (SIS) is an emerging technique for fabricating hybrid organic-inorganic materials with nanoscale precision and controlled properties. Central to SIS implementation in applications such as membranes, sensors, and functional coatings is the mechanical properties of hybrid materials in water-rich environments. This work studies the nanocomposite morphology and its effect on the mechanical behavior of SIS-based hybrid thin films of AlOx-PMMA under aqueous environments. Water-supported tensile measurements reveal an unfamiliar behavior dependent on the AlOx content, where the modulus decreases after a single SIS cycle and increases with additional cycles. In contrast, the yield stress constantly decreases as the AlOx content increases. A comparison between water uptake measurements indicates that AlOx induces water uptake from the aqueous environment, implying a "nanoeffect" stemming from AlOx-water interactions. We discuss the two mechanisms that govern the modulus of the hybrid films: softening due to increased water absorption and stiffening as the AlOx volume fraction increases. The decrease in the yield stress with SIS cycles is associated with the limited mobility and extensibility of polymer chains caused by the growth of AlOx clusters. Our study highlights the significance of developing hybrid materials to withstand aqueous or humid conditions which are crucial to their performance and durability.

Dual Role of Silicon-based Matrices in Electron Exchange Matrices for Waste Treatment.

Para chloro aniline (PCA) is a common toxic pollutant found in pharmaceutical wastewater. Our study suggests a novel PCA treatment method based on a heterogeneous advanced oxidation process (AOP) that proceeds in an electron exchange matrix (EEM) prepared by the incorporation of redox-active specie in silica matrices using the sol-gel synthesis route. The results, which are supported by DFT calculations, show that the silicon skeleton of the EEM has two important roles, both as a porous matrix that hosts the redox species and as an oxidant species involved in the AOP. The calculations indicate that the formation of a radical on the nitrogen is favored. The suggested mechanism could shed light on the AOP, which proceeds in a heterogenous system, and on its application inside the understudied EEMs that, until now, have been a virtual black box. A better understanding of the mechanism could lead to improved control over the heterogeneous processes that can play a critical role in industries with the need to treat small amounts of toxic compounds at low concentrations, such as in the pharmaceutical industry.

Bacterial Infections and Clinical Outcomes Among Febrile Infants up to 90 Days Old With SARS-CoV-2 Infection: A Multicenter Cohort Study.

We present a large, multicenter, cohort study that aimed to assess bacterial infection rates among febrile infants up to 90 days old presenting to the pediatric emergency department with severe acute respiratory syndrome coronavirus 2 infection during 2021-2022 throughout successive variant waves. Overall, 417 febrile infants were included. Twenty-six infants (6.2%) had bacterial infections. All bacterial infections consisted of urinary tract infections, and there were no invasive bacterial infections. There was no mortality.

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues.

Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by increasing drug dissolution rate and adhesion to the gastrointestinal mucus. However, the fundamental features that govern the particle-mucus interactions have not been investigated in a systematic way before. In this work, we synthesize mucin hydrogels that mimic those of freshly excised porcine mucin. By using fluorescent pure curcumin particles, we characterize the effect of particle size (200 nm, and 1.2 and 1.3 µm), concentration (18, 35, and 71 µg mL-1), and hydrogel crosslinking density on the diffusion-driven particle penetration in vitro. Next, we derive a phenomenological model that describes the physics behind the diffusion-derived penetration and considers the contributions of the key parameters assessed in vitro. Finally, we challenge our model by assessing the oral pharmacokinetics of an anti-cancer model drug, namely dasatinib, in pristine and nanonized forms and two clinically relevant doses in rats. For a dose of 10 mg kg-1, drug nanonization leads to a significant ∼8- and ∼21-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the unprocessed drug. When the dose of the nanoparticles was increased to 15 mg kg-1, the oral bioavailability increased though not significantly, suggesting the saturation of the mucus penetration sites, as demonstrated by the in vitro model. Our overall results reveal the potential of this approach to pave the way for the development of tools that enable a more rational design of nano-drug delivery systems for mucosal administration. STATEMENT OF SIGNIFICANCE: The development of experimental-theoretical tools to understand and predict the diffusion-driven penetration of particles into mucus is crucial not only to rationalize the design of nanomedicines for mucosal administration but also to anticipate the risks of the exposure of the body to nano-pollutants. However, a systematic study of such tools is still lacking. Here we introduce an experimental-theoretical approach to predict the diffusion-driven penetration of particles into mucus and investigate the effect of three key parameters on this interaction. Then, we challenge the model in a preliminary oral pharmacokinetics study in rats which shows a very good correlation with in vitro results. Overall, this work represents a robust platform for the modelling of the interaction of particles with mucosae under dynamic conditions.

Triage performance in adolescent patients with SARS-CoV-2 infection in Israel.

OBJECTIVE: The aim of this study was to assess the performance of the Pediatric Canadian Triage and Acuity Scale (PaedCTAS) in adolescent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A time-series study was conducted in the Emergency Departments (EDs) of 17 public hospitals during the Delta (B.1.617.2) variant spread in Israel. Data were collected prospectively from June 11, 2021 to August 15, 2021. Multivariate regression analyses were performed to identify independent variables associated with hospital admission and with admission to an Intensive Care Unit (ICU). RESULTS: During the study period, 305 SARS-CoV-2 patients ages 12-18 years presenting to the ED were included, and 267 (87.5%) were unvaccinated. Sixty-seven (22.0%) and 12 (3.9%) patients were admitted to pediatric wards and ICUs, respectively. PaedCTAS level 1-2 and the presence of chronic disease increased the odds of hospital admission (adjusted odds ratio (aOR) 5.74, 95% CI, 2.30-14.35, p < 0.0001), and (aOR 2.9, 95% CI, 1.48-5.67, p < 0.02), respectively. PaedCTAS level 1-2 and respiratory symptoms on presentation to ED increased the odds of ICU admission (aOR 27.79; 95% CI, 3.85-176.91, p < 0.001), and (aOR 26.10; 95% CI, 4.47-172.63, p < 0.0001), respectively. PaedCTAS level 3-5 was found in 217/226 (96%) of the patients who were discharged home from the ED. CONCLUSIONS: The findings suggest that PaedCTAS level 1-2 was the strongest factor associated with hospital and ICU admission. Almost all the patients who were discharged home had PaedCTAS level 3-5. Study findings suggest good performance of the PaedCTAS in this cohort.

Humidity-Driven Supercontraction and Twist in Spider Silk.

Spider silk is a protein material that exhibits extraordinary and nontrivial properties such as the ability to soften, decrease in length (i.e., supercontract), and twist upon exposure to high humidity. These behaviors stem from a unique microstructure in combination with a transition from glassy to rubbery as a result of humidity-driven diffusion of water. In this Letter we propose four length scales that govern the mechanical response of the silk during this transition. In addition, we develop a model that describes the microstructural evolution of the spider silk thread and explains the response due to the diffusion of water molecules. The merit of the model is demonstrated through an excellent agreement to experimental findings. The insights from this Letter can be used as a microstructural design guide to enable the development of new materials with unique spiderlike properties.

Pediatric Hospitalizations After School Reopening During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha (B.1.1.7) Variant Spread: A Multicenter Cross-sectional Study in Israel.

This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated emergency department visits and hospitalizations in pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2-related pediatric morbidity.

The influence of boundary conditions and protein availability on the remodeling of cardiomyocytes.

The heart muscle is capable of growing and remodeling in response to changes in its mechanical and hormonal environment. While this capability is essential to the healthy function of the heart, under extreme conditions it may also lead to heart failure. In this work, we derive a thermodynamically based and microscopically motivated model that highlights the influence of mechanical boundary conditions and hormonal changes on the remodeling process in cardiomyocytes. We begin with a description of the kinematics associated with the remodeling process. Specifically, we derive relations between the macroscopic deformation, the number of sarcomeres, the sarcomere stretch, and the number of myofibrils in the cell. We follow with the derivation of evolution equations that describe the production and the degradation of protein in the cytosol. Next, we postulate a dissipation-based formulation that characterizes the remodeling process. We show that this process stems from a competition between the internal energy, the entropy, the energy supplied to the system by ATP and other sources, and dissipation mechanisms. To illustrate the merit of this framework, we study four initial and boundary conditions: (1) a myocyte undergoing isometric contractions in the presence of either an infinite or a limited supply of proteins and (2) a myocyte that is free to dilate along the radial direction with an infinite and a limited supply of proteins. This work underscores the importance of boundary conditions on the overall remodeling response of cardiomyocytes, suggesting a plausible mechanism that might play a role in distinguishing eccentric vs. concentric hypertrophy.

On-Demand Manufacturing Capabilities of Mussels Enable Robust Adhesion to Geometrically Complex Surfaces.

Marine mussels have the remarkable ability to adhere to a variety of natural and artificial surfaces under hostile environmental conditions. Although the molecular composition of mussel adhesives has been well studied, a mechanistic understanding of the physical origins of mussels' impressive adhesive strength remains elusive. Here, we investigated the role of substrate geometry in the adhesive performance of mussels. Experimentally, we created substrates with differing surface properties using 3D printing and laser drilling and introduced these to mussels, which in turn adhered to the engineered surfaces via plaque-thread byssal structures. Tensile testing with in situ imaging was conducted to quantify the adhesion strength of the mussel plaques, and the microstructures of the mechanically deformed plaques were characterized using scanning electron microscopy. Our results reveal that the geometry of the surfaces has no significant impact on the detachment force and the strain, whereas the change in adhesion area leads to a different adhesion stress. Ultrastructural analysis confirms the expected presence of an open-cell foamy network coated with the cuticle. The observed detachment dynamics and failure mechanisms do vary depending on the substrate properties, suggesting the presence of substrate-dependent nonuniform stress distributions at the interface. Together, these results show mussels' remarkable ability to adapt to differing physical conditions and demonstrate the importance of the on-demand and in situ manufacturing of the stiff cuticle and relatively compliant adhesive interlayer. The resultant composite structure avoids the formation of prestress during the formation of the adhesive joint, provides conformability to the surface, and helps compensate for local bending interactions to maintain adhesive strength. Our findings suggest forward design strategies to improve adhesive performance on complex surfaces.

Thin Layer Buckling in Perovskite CsPbBr3 Nanobelts.

Flexible semiconductor materials, where structural fluctuations and transformation are tolerable and have low impact on electronic properties, focus interest for future applications. Two-dimensional thin layer lead halide perovskites are hailed for their unconventional optoelectronic features. We report structural deformations via thin layer buckling in colloidal CsPbBr3 nanobelts adsorbed on carbon substrates. The microstructure of buckled nanobelts is determined using transmission electron microscopy and atomic force microscopy. We measured significant decrease in emission from the buckled nanobelt using cathodoluminescence, marking the influence of such mechanical deformations on electronic properties. By employing plate buckling theory, we approximate adhesion forces between the buckled nanobelt and the substrate to be Fadhesion ∼ 0.12 µN, marking a limit to sustain such deformation. This work highlights detrimental effects of mechanical buckling on electronic properties in halide perovskite nanostructures and points toward the capillary action that should be minimized in fabrication of future devices and heterostructures based on nanoperovskites.

Tuning the response of fluid filled hydrogel core-shell structures.

Hydrogels are hydrophilic polymer networks that swell upon submersion in water. Thanks to their bio-compatibility, compliance, and ability to undergo large deformations, hydrogels can be used in a wide variety of applications such as in situ sensors for measuring cell-generated forces and drug delivery vehicles. In this work we investigate the equilibrium mechanical responses that can be achieved with hydrogel-based shells filled with a liquid core. Two types of gel shell geometries are considered - a cylinder and a spherical shell. Each shell is filled with either water or oil and subjected to compressive loading. We illustrate the influence of the shell geometry and the core composition on the mechanical response of the structure. We find that all core-shell structures stiffen under increasing compressive loading due to the load-induced expulsion of water molecules from the hydrogel shell. Furthermore, we show that cylindrical core-shell configurations are stiffer then their spherical equivalents. Interestingly, we demonstrate that the compression of a core-shell structure with an aqueous core leads to the transportation of water molecules from the core into the hydrogel. These results will guide the design of novel core-shell structures with tunable properties and mechanical responses.

The effects of aging on the mechanical properties of the vitreous.

The vitreous body is a viscoelastic gel-like network that fills the space between the lens and the retina in the eye. With aging, the vitreous undergoes a liquefaction process in which liquid pockets form in the gel network, thereby motivating the detachment of the vitreous from the retina in a process known as posterior vitreous detachment (PVD). The PVD process may lead to the formation of floaters and even result in partial or complete loss of vision. Experiments show that the liquefaction and the PVD processes alter the mechanical properties of the vitreous. In this work, we propose a microscopically motivated model that characterizes the changes in the mechanical properties of the vitreous due to aging. To this end, we distinguish between four vitreous states: a homogeneous vitreous, a liquefied vitreous, a vitreous that undergoes partial PVD, and a vitreous with full PVD. The model predicts the time-dependent and the steady-state response of the vitreous in each of the four states. The proposed framework is validated through a comparison with various experimental findings and captures the softening of the vitreous due to aging. We illustrate the importance of the age at which the PVD process begins and of the rate of the detachment process. In addition, we introduce a quantifiable parameter that describes the stage of PVD in the eye. Lastly, we employ our model to investigate the possibility of restoring the mechanical properties of a vitreous that has undergone PVD through the addition of reinforcing fibers to the gel. This work provides insight into the consequences of the age-related changes in the microstructure of the eye and serves as a motivation for new therapeutic measures.

On the Origin of Supercontraction in Spider Silk.

Spider silk is a protein material that exhibits extraordinary and nontrivial properties such as the ability to soften and decrease its length by up to ∼60% upon exposure to high humidity. This process is commonly called supercontraction and is the result of a transition from a highly oriented glassy phase to a disoriented rubbery phase. In this work, we derive a microscopically motivated and energy-based model that captures the underlying mechanisms that give rise to supercontraction. We propose that the increase in relative humidity and the consequent wetting of a spider silk have two main consequences: (1) the dissociation of hydrogen bonds and (2) the swelling of the fiber. From a mechanical viewpoint, the first consequence leads to the formation of rubbery domains. This process is associated with an entropic gain and a loss of orientation of chains in the silk network, which motivates the contraction of the spider silk. The swelling of the fiber is accompanied by the extension of chains in order to accommodate the influx of water molecules. Supercontraction occurs when the first consequence is more dominant than the second. The model presented in this work allows us to qualitatively track the transition of the chains from glassy to rubbery states and determine the increase in entropy, the loss of orientation, and the swelling as the relative humidity increases. We also derive explicit expressions for the stiffness and the mechanical response of a spider silk under given relative humidity conditions. To illustrate the merit of this model, we show that the model is capable of capturing several experimental findings. The insights from this work can be used as a microstructural design guide to enable the development of new materials with unique spider-like properties.

A Microscopically Motivated Model for Particle Penetration into Swollen Biological Networks.

Biological gels (bio-gels) are hydrated polymer networks that serve diverse biological functions, which often lead to intentional or unintentional exposure to particulate matter. In this work, we derive a microscopically motivated framework that enables the investigation of penetration mechanisms into bio-gels. We distinguish between two types of mechanisms: spontaneous (unforced) penetration and forced penetration. Using experimental data available in the literature, we exploit the proposed model to characterize and compare between the microstructures of respiratory, intestinal, and cervicovaginal mucus and two types of biofilms. Next, we investigate the forced penetration process of spherical and ellipsoidal particles into a locally quadrilateral network. The proposed framework can be used to improve and complement the analysis of experimental findings in vitro, ex vivo, and in vivo. Additionally, the insights from this work pave the way towards enhanced designs of nano-medicines and allow the assessment of risk factors related to the nano-pollutants exposure.

Rapid analysis of cell-generated forces within a multicellular aggregate using microsphere-based traction force microscopy.

We present a new approach to measuring cell-generated forces from the deformations of elastic microspheres embedded within multicellular aggregates. By directly fitting the measured sensor deformation to an analytical model based on experimental observations and invoking linear elasticity, we dramatically reduce the computational complexity of the problem, and directly obtain the full 3D mapping of surface stresses. Our approach imparts extraordinary computational efficiency, allowing tractions to be estimated within minutes and enabling rapid analysis of microsphere-based traction force microscopy data.

Giant Superelastic Piezoelectricity in Flexible Ferroelectric BaTiO3 Membranes.

Mechanical displacement in commonly used piezoelectric materials is typically restricted to linear or biaxial in nature and to a few percent of the material dimensions. Here, we show that free-standing BaTiO3 membranes exhibit nonconventional electromechanical coupling. Under an external electric field, these superelastic membranes undergo controllable and reversible "sushi-rolling-like" 180° folding-unfolding cycles. This crease-free folding is mediated by charged ferroelectric domains, leading to giant >3.8 and 4.6 µm displacements for a 30 nm thick membrane at room temperature and 60 °C, respectively. Further increasing the electric field above the coercive value changes the fold curvature, hence augmenting the effective piezoresponse. Finally, it is found that the membranes fold with increasing temperature followed by complete immobility of the membrane above the Curie temperature, allowing us to model the ferroelectric domain origin of the effect.

Force distribution and multi-scale mechanics in smooth muscle tissues.

The mechanical role of smooth muscle tissue in many physiological processes is vital to their healthy function. In this work, we provide a deeper understanding of the underlying mechanisms that govern the smooth muscle tissue response. Specifically, we model and investigate the distribution and the transmission of passive and active forces throughout the microstructure. Broadly, smooth muscle cells contain a structural network with two types of load carrying structures: (1) contractile units made of actin and myosin filaments, which are capable of generating force, and (2) intermediate filaments. The extracellular matrix comprises elastin and collagen fibers that can sustain stress. We argue that all of the load carrying constituents in the tissue participate in the generation and the transmission of passive and active forces. We begin by modeling the response of the elements in the smooth muscle cell and defining a network of contractile units and intermediate filaments through which forces are transferred. This allows to derive an expression for the stress that develops in the cell. Next, we assume a hyperelastic behavior for the extracellular matrix and determine the stress in the tissue. With appropriate kinematic constraints and equilibrium considerations, we relate the macroscopic deformation to the stretch of the individual load carrying structures. Consequently, the stress on each element in the tissue can be computed. To validate the framework, we consider a simple microstructure of a smooth muscle tissue and fit the model parameters to experimental findings. The framework is also used to delineate experimental evidence which suggests that the suppression of intermediate filaments reduces the active and passive forces in a tissue. We show that the degradation and the reduction of the number of intermediate filaments in the cell fully explains this observation.

Molecular Mechanics of Beta-Sheets.

ß-Sheet protein structures and domains are widely found in biological materials such as silk. These assemblies play a major role in the extraordinary strength and unique properties of biomaterials. At the molecular level, the single ß-sheet structure comprises polypeptide chains in zig-zag conformations that are held together by hydrogen bonds. ß-sheet domains comprise multiple ß-sheets that originate from hydrophobic interactions between sheets and are held together by van der Waals interactions. In this work, we introduce molecular models that capture the response of such domains upon mechanical loading and illustrate the mechanisms behind their collapse. We begin by modeling the force that is required to pull a chain out of a ß-sheet. Next, we employ these models to study the behavior of ß-sheets that are embedded into and connected to an amorphous protein matrix. We show that the collapse of a ß-sheet occurs upon the application of a sufficiently high force that is transferred from the chains in the matrix to individual chains of the ß-sheet structure and causes shear. With the aim of understanding the response of ß-sheet domains, we derive models for the interactions between ß-sheets. These enable the study of critical forces required to break such domains. As opposed to molecular dynamics simulations, the analysis in this work yields simple expressions that shed light on the relations between the nanostructure of ß-sheet domains and their mechanical response. In addition, the findings of this work suggest how ß-sheet domains can be strengthened.

The prevalence of primary dysmenorrhea among students and its association with musculoskeletal and myofascial pain.

OBJECTIVES: To examine the association between dysmenorrhea and musculoskeletal pain amongst university students aged 20-35 and the association between dysmenorrhea and the occurrence of MTrPs. METHODS: The study comprised two stages: a cross-sectional study evaluated the association between dysmenorrhea and musculoskeletal pain and a case-control study evaluated the association between dysmenorrhea and the occurrence of MTrPs in the abdominal and pelvic area. Initially, questionnaires such as demographics, menstruation characteristics, Numeric Pain Rating Scale (NPRS), measuring the average pain during menstruation and Nordic, were distributed to female students. Twenty subjects who suffered from menstrual pain of >3 on the NPRS (ones with the highest scores) were included in the second stage as cases. An additional 20 who had not suffered from menstrual pain (NPRS ≤3) were considered controls. All 40 subjects underwent an assessment of MTrPs by two examiners blinded to each other's results and to the group allocation of the subjects. RESULTS: We found that dysmenorrhea is a very prevalent condition among young female students. Most frequent complaints were: lower abdomen and back pain, tiredness, breast tenderness, mood changes, and an increased appetite. Pain during menstruation indicated a significant positive association with neck, low back, and hip/thigh pain during the last 12 months. The results of the palpitation conclusively showed more active MTrPs in the rectus abdominis, quadratus lumborum and paraspinal muscles in women suffering from pain during menstruation than in those who were not in pain. CONCLUSION: Our data provide an initial basis for the inclusion of a myofascial examination when evaluating women with dysmenorrhea.

Force distribution and multiscale mechanics in the mussel byssus.

The byssi of sessile mussels have the extraordinary ability to adhere to various surfaces and withstand static and dynamic loadings arising from hostile environmental conditions. Many investigations aimed at understanding the unique properties of byssal thread-plaque structures have been conducted and have inspired the enhancement of fibre coatings and adhesives. However, a systems-level analysis of the mechanical performance of the composite materials is lacking. In this work, we discuss the anatomy of the byssus and the function of each of the three components (the proximal thread portion, the distal thread portion and the adhesive plaque) of its structures. We introduce a basic nonlinear system of springs that describes the contribution of each component to the overall mechanical response and use this model to approximate the elastic modulus of the distal thread portion as well as the plaque, the response of which cannot be isolated through experiment alone. We conclude with a discussion of unresolved questions, highlighting areas of opportunity where additional experimental and theoretical work is needed. This article is part of the theme issue 'Transdisciplinary approaches to the study of adhesion and adhesives in biological systems'.