Intestinal mucus provides a significant barrier to transport of orally delivered drug carriers, as well as other particulates (e.g. food, microbes). The relative significance of particle size, ...surface chemistry, and dosing medium to mucus barrier properties is not well characterized, but important in designing delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20-500 nm diameter carboxylate- and polyethylene glycol-(PEG-)functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer versus a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with an increasing particle size less than and more than theoretically (Stokes-Einstein) expected in a homogenous medium when dosed in buffer and model-fed state intestinal contents, respectively. For example, effective diffusivity decreased 2.9- versus 20-fold with increase in the particle size from 100 to 500 nm when dosed to mucus in buffer versus lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in a dosing medium. The results indicate that reduction of particle size may increase particle transport through intestinal mucus barriers, but these effects are strongly dependent on intestinal contents and particle surface chemistry.
This study aimed to investigate the relationship between the micro structural properties of the subchondral trabecular bone (STB) and the macro mechanical properties of the articular cartilage (AC) ...in patients with osteoporotic (OP) and osteopenic (OPE) fractures. Sixteen femoral head samples (OP;OPE,
n
= 8 each) were obtained from female patients who underwent hip hemiarthroplasty. STB and AC specimens were harvested from those heads. Bone specimens were scanned using µ-CT to determine the micro structural properties. In-situ nondestructive compressive tests were performed for the cartilages to obtain elastic properties. The finite element technique was implemented on STB models created from µ-CT data to compute apparent elastic modulus. In addition, dynamic cyclic destructive tests were performed on STB and AC specimens to assess failure cycles. The results demonstrated that STB specimens in OPE group have more interconnected structure and higher cyclic dynamic strength than those in OP group. Furthermore, bone mineral density, failure cycle, and trabecular number of STB were positively correlated with the cartilage failure cycle, which indicates that STB alteration may affect the macroscopic mechanical properties of AC. The findings suggest that STB loss correlates with a decrease in cartilage strength and that improving of bone quality may prevent cartilage weakness.
Violence related injuries and deaths mostly caused by firearms are a major problem throughout the world. Understanding the factors that control the extent of hard-soft tissue wound patterns using ...computer imaging techniques, numerical methods, and machine learning algorithms may help physicians to diagnose and treat those injuries more properly. Here, we investigate the use of computational results coupled with the pattern recognition algorithms to develop an approach for forensic applications. Initially, computer tomography (CT) images of the patient whose leg was shot by a 9 × 19 parabellum bullet are used to construct the FE models of that patient's femoral bone and the surrounding soft tissues. Then, Hounsfield units-based material properties are assigned to elements of the bone. To simulate the full range of loading conditions encountered in ballistic events, a constitutive model that captures the strain-rate dependent response is implemented. The entrance pathway vector of the bullet is directed in accordance with the patient's wound and the simulations are deployed for the cases having various inlet velocities such as 150, 200, 250, 300, and 350 m/s. Once the FE results for each case are obtained, they are processed with supervised machine learning algorithms to classify the wound and inlet velocity correspondence. The results demonstrate that they can be diagnosed with a percent accuracy of 97.3, 97.5, and 98.3 for the decision tree (DT),
-nearest neighbors (kNN) and support vector machine (SVM) classifier, respectively. This approach may provide a useful framework in classifying the wound type, predicting the bullet impact velocity and its firing distance.
Purpose
Although the fresh frozen (FF) cadaver is preferred for surgical applications, it is limited due to short usage time, unsuitable for reuse and the risk of infection. Due to its limited use, ...FF cadavers, which are covered by import in countries with insufficient body donation cause low-cost effectiveness. With the increase of real human tissue specimen necessities for surgical training, long-term preservation of the cadavers is crucial due to changes in mechanical properties. Therefore, studies on embalming solutions have increased in recent years.
Methods
We quantify the biomechanical properties of human parietal bones preserved via modified larssen solution (MLS) and compare the results with the specimens preserved as FF and fixed with 10% formalin-based solution (F10). The rectangular samples of 24 parietal bones of male individuals were resected from MLS-embalmed, F10-embalmed and FF cadavers to form three groups each containing eight samples. These specimens were tested longitudinally to identify mechanical properties.
Results
The tensile test results showed that there is not a significant difference between the groups in terms of stiffness, elastic modulus, strain at ultimate stress, failure strain and effective plastic strain. However, the yield stress, ultimate stress, yield strain, failure stress and total energy and post-yield properties are significantly lower in F10 than MLS and FF groups.
Conclusion
It is observed that the mechanical properties of MLS preserved and FF parietal bones have almost similar properties. Thus, it can be concluded that MLS is a suitable fixative solution for bone studies and bone-related surgical anatomy training applications.
Airborne gravimetry with strapdown inertial sensors has been a valuable tool for many years to fill in the gravity data gaps on the areas not accessible by land. Accuracies of 1 mGal level with ...off-the-shelf navigation-grade inertial measurement units (IMU) can only be achieved provided that the accelerometer drifts mainly caused by the temperature variations inside the IMU housing are separated from the gravity signal. Although there are several strategies proposed in the literature to deal with this inseparability problem, we use a thermal stabilization system (iTempStab) added on an iNAT-RQH navigation-grade IMU and investigate its performance over a test region in central Turkey with moderate topography and highly qualified ground truth gravity data. Two test flights were performed in 2017 and 2018 with and without iTempStab add-on following almost the same flight trajectories. During the first flight in 2017 with iNAT-RQH only, which lasted almost 5.5 h, there were considerable temperature variations inside the IMU housing from 39.1 to 46.0 °C. A simple thermal correction based on a laboratory calibration done before the flight was applied to the vertical Z-accelerometer in the pre-processing stage. However, temperature changes were within 0.1 °C during the second test flight in 2018 with TempStab add-on. The temperature stabilization gained by the iTempStab add-on produced better cross-over statistics. While the RMSE of the non-adjusted cross-over residuals was about 2.6 mGal, it reduced by 50% with iTempStab add-on. The adjusted cross-over differences of the 2018 flight yielded an RMSE of about 0.5 mGal, which is a remarkable precision for the strapdown gravimetry. The comparison with upward continued ground gravity data at flight altitudes suggests that the thermal stabilization system shows also remarkable improvements in the residual statistics. The range of the residuals decreases from ± 10 to ± 5 mGal, the standard deviation decreases from 2.19 to 0.94 mGal, and the RMSE decreases from 2.24 to 1.48 mGal, respectively, with the iTempStab add-on. It can be concluded that the thermal stabilization system significantly improves the accelerometer stability and therefore the precision and accuracy of the strapdown airborne gravity estimates.
Abstract Orally delivered drugs and nutrients must diffuse through mucus to enter the circulatory system, but the barrier properties of mucus and their modulation by physiological factors are ...generally poorly characterized. The main objective of this study was to examine the impact of physicochemical changes occurring upon food ingestion on gastrointestinal (GI) mucus barrier properties. Lipids representative of postprandial intestinal contents enhanced mucus barriers, as indicated by a 10–142-fold reduction in the transport rate of 200 nm microspheres through mucus, depending on surface chemistry. Physiologically relevant increases in Ca2+ resulted in a 2–4-fold reduction of transport rates, likely due to enhanced cross-linking of the mucus gel network. Reduction of pH from 6.5 to 3.5 also affected mucus viscoelasticity, reducing particle transport rates approximately 5–10-fold. Macroscopic visual observation and micro-scale lectin staining revealed mucus gel structural changes, including clumping into regions into which particles did not penetrate. Histological examination indicated food ingestion can prevent microsphere contact with and endocytosis by intestinal epithelium. Taken together, these results demonstrate that GI mucus barriers are significantly altered by stimuli associated with eating and potentially dosing of lipid-based delivery systems; these stimuli represent broadly relevant variables to consider upon designing oral therapies.
Mucus forms a protective hydrogel layer over the intestinal epithelium, presenting a selective and robust barrier to the uptake of particulates and microbe invasion. Disease can alter mucus ...production and composition, thus potentially modifying mucosal barrier properties. Hirschsprung's disease (HD) is a developmental abnormality of the nervous system often complicated by intestinal infection. An investigation of colonic mucus barrier properties in an HD animal model, endothelin receptor B mutant mice, revealed significantly reduced microsphere (passive) and microbe (active) transport rates (7‐fold and 3.6‐fold, respectively, in proximal colonic mucus) relative to wild‐type. Transport differences were evident in both the ganglionic and aganglionic colon segments, in agreement with the risk of HD‐associated enterocolitis after surgery to remove aganglionic colon segments. The development of therapies aimed at altering colonic mucus barrier properties could be explored towards preventing the onset of enterocolitis in HD.
Microparticle and microbial transport through colonic mucus are reduced in an animal model of Hirschsprung's disease (HD) (7‐fold and 3.6‐fold, respectively). Mucus barrier differences extended beyond the aganglionic colon segment, consistent with development of enterocolitis after surgical removal of aganglionic colon. Therapies geared toward altering the mucus barrier could be explored for preventing HD associated enterocolitis.
Wettability has a significant impact on the flow of oil during enhanced oil recovery (EOR) and profound effect on fluid distribution in oil fields. Mechanisms that influence the interaction between ...the injected water and the components of crude oil in the presence of carbonate rock samples were investigated. The main objectives of this study were to investigate the role of both rock mineralogy and the compositions of various oils as a function of asphaltene content on the destabilization of the aqueous film separating the oil from the substrate rock surface of carbonates using aqueous phases such as brine and carbonated water. The contact angles as a function of time were measured using brine and carbonated water and two types of crude oil on four types of rock samples. Once the exact contact angle has been determined, the compositions of various oils, based on asphaltene contents, were characterized to investigate the role of oil composition on the destabilization of the aqueous film separating the oil from the rock surface. Interfacial tensions (IFTs) of brine and two types of crude oil were also measured. Four types of rock samples from carbonate reservoirs, with different compositions, selected based on X-ray diffraction results were as follows: (1) 100% dolomite D(100), (2) 100% calcite C(100), (3) 67% dolomite + 33% calcite (D67 + C33), and (4) 37% dolomite + 63% calcite (D37 + C63). Two types of crude oil were used based on the asphaltene content obtained using the saturate, aromatic, resin, and asphaltene analysis. The contents of asphaltenes for crude-1 and crude-2 were 11.6 and 6.4 wt % and represented as (I-11.6) and (II-6.4), respectively. In this study, crude oil/brine/carbonate systems showed that (D37 + C63) gave the lowest contact angle value of 67° with 6.4 wt % of asphaltene content (II-6.4) and that D(100) gave the highest contact angle of 136° with 11.6 wt % of asphaltene content (I-11.6). Brine was used as the external phase on both tests. On the other hand, using carbonated water as the external phase, the contact angle decreased from 97.6° (D67 + C33) to 75.5° (D37 + C63) for mixed dolomite/calcite systems. Decreasing the dolomite content in mixed dolomite/calcite systems caused a shift in contact angle from the oil negative intermediate wet to weakly water wet regardless of the saturating fluid phase. Also, using the adhesion tension approach, in defining surface wettability, shows that with the decrease in the contact angle values, adhesion tension shifted to positive directions with an increase in the degree of water wetness. This behavior was mainly due to the effect of type-II crude oil. The novelty of this study stems from studying the effect of rock mineralogy based on dolomite and calcite distribution and oil composition based on the asphaltene content in wettability alteration using aqueous phases such as brine and carbonated water. The results of both contact angle and IFT were implemented in adhesion tension using the Thomas Young equation as an alternative approach in defining surface wettability. This study will provide a better understanding of mineralogy/fluid/interaction, which is very crucial in the optimization of water injection and wettability reversal during the EOR process.
Mucus constitutes a protective layer which coats the gastrointestinal tract, controlling interactions of both commensal and pathogenic microbes with underlying tissues. Changes to the mucus barrier, ...for example due to altered mucin expression or external stimuli, may impact interactions with microbes and thus potentially contribute to altered gut homeostasis, onset of inflammation, or pathogen invasion. Food-associated stimuli, including lipids, have been shown to change mucus barrier properties and reduce transport of model drug carriers through mucus. Here, we explore the impact of lipids, specifically triglycerides in a model intestinal medium mimicking a fed state, on Escherichia coli (E. coli) transport through mucus by directly imaging swimming patterns and analyzing associated changes in mucus structure. Lipids in model fed state intestinal contents reduced E. coli speed and track linearity within mucus. These changes may be due in part to changes in molecular interactions within the mucus network as well as crowding of the mucus network by lipid emulsion droplets, which visibly stay intact in the mucus gel. In addition, observed physical interactions between bacteria and lipid structures may impact microbial speed and trajectories. As lipids are normal food components and thus represent safe, mild stimuli, these results support exploration of lipid-based strategies to alter the mucus barrier to control interactions with microbes and potentially prevent microbial invasion of underlying epithelium.
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