Chronic Shoulder Dislocation on the Unaffected Side of a Patient With Hemiparesis.

Chronic shoulder dislocation has been noted to be difficult to cure due to concomitant injuries of the soft tissue, articular cartilage, and bone. The present study reports a rare case of a patient with hemiparesis suffering chronic shoulder dislocation on the unaffected side. The patient was a 68-year-old female. She developed left hemiparesis due to cerebral bleeding at 36 years of age. Her right shoulder was dislocated for three months. A computed tomography scan and magnetic resonance imaging (MRI) showed a significant anterior glenoid defect, and the subscapularis, supraspinatus, and infraspinatus were atrophic. An open reduction with transfer of the coracoid, Latarjet's method was performed. The rotator cuffs were simultaneously repaired using McLaughlin's method. The glenohumeral joint was temporarily fixed with Kirschner wires for three weeks. There was no redislocation during the 50-month follow-up period. Even though radiographs noted progression of osteoarthritis in the glenohumeral joint, the patient reacquired shoulder function for ativities of daily living including weight-bearing ability.

Snap buckling of bistable beams under combined mechanical and magnetic loading.

We investigate the mechanics of bistable, hard-magnetic, elastic beams, combining experiments, finite-element modelling (FEM) and a reduced-order theory. The beam is made of a hard magneto-rheological elastomer, comprising two segments with antiparallel magnetization along the centreline, and is set into a bistable curved configuration by imposing an end-to-end shortening. Reversible snapping is possible between these two stable states. First, we experimentally characterize the critical field strength for the onset of snapping, at different levels of end-to-end shortening. Second, we perform three-dimensional FEM simulations using the Riks method to analyse high-order deformation modes during snapping. Third, we develop a reduced-order centreline-based beam theory to rationalize the observed magneto-elastic response. The theory and simulations are validated against experiments, with an excellent quantitative agreement. Finally, we consider the case of combined magnetic loading and poking force, examining how the applied field affects the bistability and quantifying the maximum load-bearing capacity. Our work provides a set of predictive tools for the rational design of one-dimensional, bistable, magneto-elastic structural elements. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

Self-Assembled Structure of α-Isostearyl Glyceryl Ether Affects Skin Permeability-a Lamellar with 70-nm Spaces and L3 Phase Enhanced the Transdermal Delivery of a Hydrophilic Model Drug.

Self-assembled surfactant structures, such as liquid crystals, have the potential to enhance transdermal drug delivery. In the present study, the pseudo-ternary system of GET (composed of α-Isostearyl glyceryl ether (GEIS) and polysorbate 60)/1,3 butanediol (BG)/water) was shown to exhibit a complex phase diagram. Small- and wide-angle X-ray scattering (SWAXS) and freeze-fracture transmission electron microscopy (FF-TEM) revealed that GET6BG60 (6%GET/60%BG/34%Water) formed a lamellar phase with a repeated distance of approximately 72 nm. Such a long-repeated distance of the lamellar phase was unique in the surfactant system. Moreover, the various structures, such as multilamellar vesicles and branched-like layers, were observed, which suggested that they might be deformable. On the other hand, only core-shell particles were observed in GET6BG20, the core of which was an L3 phase. GET6BG20 and GET6BG60 significantly enhanced the skin permeation of the hydrophilic model drug, antipyrine (ANP) (log Ko/w, - 1.51). However, their permeation profiles were distinct. Liquid chromatography-tandem mass spectrometry revealed that epidermal accumulation of GEIS was significantly higher with GET6BG60 than GET6BG20 after 1.5 h of permeation, which might be attributed to differences in their deformable properties. Furthermore, GEIS was reported to affect intercellular lipids. Accumulated GEIS in the epidermis may have interacted with intercellular lipids and enhanced the transdermal delivery of ANP. The difference in the permeation profiles of ANP may be attributed to the penetration process of GEIS in the epidermis. This study suggests that GET6BG20 and GET6BG60 are unique carriers to enhance the permeation of hydrophilic drugs, such as ANP.

Erratum: Twist-Induced Snapping in a Bent Elastic Rod and Ribbon [Phys. Rev. Lett. 122, 114301 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.122.114301.

Wetting dynamics of viscoelastic solid films.

We study the wetting phenomena of a soft viscoelastic solid film on a smooth and flat substrate. A poly-dimethylsiloxane (PDMS) rubber film is suspended from a stage at both ends, and the wetting behavior of the film against a glass substrate is observed while lowering the stage at a constant velocity. We find that the dynamics of the rubber-glass-air contact lines vary with the lowering velocity of the stage. When the stage velocity is sufficiently low, the film wets the substrate smoothly and the contact lines are straight throughout. Consequently, the contact line velocity is proportional to the lowering velocity. As the stage velocity is increased, the contact line velocity reaches a maximum at the critical stage velocity and then subsequently decreases. The contact lines are wavy and sensitive to the defects above the critical velocity, resulting in the trapping of air bubbles at the interface. We reproduce the wetting behavior using a simple numerical model, assuming an upper limit for the contact line velocity. The wetting behavior observed in our experiments is attributed to the transition in the in-plane stress state from tensile to compressive along the film, leading to buckling of the film above the critical stage velocity. Our results suggest the existence and importance of the maximum wetting velocity for viscoelastic solids.

Generation of the tumor-suppressive secretome from tumor cells.

Rationale: The progression of cancer cells depends on the soil and building an inhibitory soil might be a therapeutic option. We previously created tumor-suppressive secretomes by activating Wnt signaling in MSCs. Here, we examined whether the anti-tumor secretomes can be produced from tumor cells. Methods: Wnt signaling was activated in tumor cells by overexpressing ß-catenin or administering BML284, a Wnt activator. Their conditioned medium (CM) was applied to cancer cells or tissues, and the effects of CM were evaluated. Tumor growth in the mammary fat pad and tibia in C57BL/6 female mice was also evaluated through µCT imaging and histology. Whole-genome proteomics analysis was conducted to determine and characterize novel tumor-suppressing proteins, which were enriched in CM. Results: The overexpression of ß-catenin or the administration of BML284 generated tumor-suppressive secretomes from breast, prostate and pancreatic cancer cells. In the mouse model, ß-catenin-overexpressing CM reduced tumor growth and tumor-driven bone destruction. This inhibition was also observed with BML284-treated CM. Besides p53 and Trail, proteomics analysis revealed that CM was enriched with enolase 1 (Eno1) and ubiquitin C (Ubc) that presented notable tumor-suppressing actions. Importantly, Eno1 immunoprecipitated CD44, a cell-surface adhesion receptor, and its silencing suppressed Eno1-driven tumor inhibition. A pan-cancer survival analysis revealed that the downregulation of MMP9, Runx2 and Snail by CM had a significant impact on survival outcomes (p < 0.00001). CM presented a selective inhibition of tumor cells compared to non-tumor cells, and it downregulated PD-L1, an immune escape modulator. Conclusions: The tumor-suppressive secretome can be generated from tumor cells, in which ß-catenin presented two opposing roles, as an intracellular tumor promoter in tumor cells and a generator of extracellular tumor suppressor in CM. Eno1 was enriched in CM and its interaction with CD44 was involved in Eno1's anti-tumor action. Besides presenting a potential option for treating primary cancers and metastases, the result indicates that aggressive tumors may inhibit the growth of less aggressive tumors via tumor-suppressive secretomes.

Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone.

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or ß-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/ß-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4.

Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone. However, whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown. We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells. The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis, markedly reduced the progression of the brain tumors. The simultaneous application of fluphenazine (FP), an antipsychotic dopamine modulator, enhanced tumor suppression. Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2, respectively. Notably, dopamine downregulated Lrp5 via DRD1 in tumor cells. A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven, dopamine-mediated tumor suppression. The silencing of Lrp5 reduced CCN4, and the administration of CCN4 elevated oncogenic genes such as MMP9, Runx2, and Snail. In summary, this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1, indicating the possibility of developing an adjuvant bone-mediated loading therapy.

Mechanics of two filaments in tight orthogonal contact.

Networks of flexible filaments often involve regions of tight contact. Predictively understanding the equilibrium configurations of these systems is challenging due to intricate couplings between topology, geometry, large nonlinear deformations, and friction. Here, we perform an in-depth study of a simple, yet canonical, problem that captures the essence of contact between filaments. In the orthogonal clasp, two filaments are brought into contact, with each centerline lying in one of a pair of orthogonal planes. Our data from X-ray tomography (µCT) and mechanical testing experiments are in excellent agreement with finite element method (FEM) simulations. Despite the apparent simplicity of the physical system, the data exhibit strikingly unintuitive behavior, even when the contact is frictionless. Specifically, we observe a curvilinear diamond-shaped ridge in the contact-pressure field between the two filaments, sometimes with an inner gap. When a relative displacement is imposed between the filaments, friction is activated, and a highly asymmetric pressure field develops. These findings contrast to the classic capstan analysis of a single filament wrapped around a rigid body. Both the µCT and FEM data indicate that the cross-sections of the filaments can deform significantly. Nonetheless, an idealized geometrical theory assuming undeformable tube cross-sections and neglecting elasticity rationalizes our observations qualitatively and highlights the central role of the small, but nonzero, tube radius of the filaments. We believe that our orthogonal clasp analysis provides a building block for future modeling efforts in frictional contact mechanics of more complex filamentary structures.

Inhibition of the Growth of Breast Cancer-Associated Brain Tumors by the Osteocyte-Derived Conditioned Medium.

The brain is a common site of metastasis from advanced breast cancer but few effective treatments are available. We examined a therapeutic option with a conditioned medium (CM), focusing on the role of Lrp5 and ß-catenin in Wnt signaling, and IL1ra in osteocytes. Osteocytes presented the innate anti-tumor effect and the overexpression of the above genes strengthened their action. In a mouse model, the injection of their CM inhibited mammary tumors and tumor-driven osteolysis. Importantly, Lrp5- and/or IL1ra-overexpressing osteocytes or the local administration of ß-catenin-overexpressing CM markedly inhibited brain tumors. In the transport analysis, tumor-suppressing factors in CM were shown to diffuse through the skull. Mechanistically, the CM with overexpression of the above genes downregulated oncogenic genes such as MMP9, Runx2, TGFß, and Snail in breast cancer cells. Also, the CM with ß-catenin overexpression downregulated CXCL1 and CXCL5 and upregulated tumor suppressors such as LIMA1, DSP, p53, and TRAIL in breast cancer cells. Notably, whole-genome proteomics revealed that histone H4 was enriched in CM and acted as an atypical tumor suppressor. Lrp5-overexpressing MSCs were also shown to act as anti-tumor agents. Collectively, this study demonstrated the therapeutic role of engineered CM in brain tumors and the tumor-suppressing action of extracellular histone H4. The result sheds light on the potential CM-based therapy for breast cancer-associated brain metastases in a minimally invasive manner.

Mechanical stimulations can inhibit local and remote tumor progression by downregulating WISP1.

Mechanical stimulations can prevent bone loss, but their effects on the tumor-invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored mainly through urine. Urine samples were also collected from human subjects before and after step aerobics. The result showed that knee loading inhibited tumor progression in the loaded tibia. Notably, it also reduced remotely the growth of mammary tumors. In the urine, an altered level of cholesterol was observed with an increase in calcitriol, which is synthesized from a cholesterol derivative. In urinary proteins, knee loading in mice and step aerobics in humans markedly reduced WNT1-inducible signaling pathway protein 1, WISP1, which leads to poor survival among patients with breast cancer. In the ex vivo breast cancer tissue assay, WISP1 promoted the growth of cancer fragments and upregulated tumor-promoting genes, such as Runx2, MMP9, and Snail. Collectively, the present preclinical and human study demonstrated that mechanical stimulations, such as knee loading and step aerobics, altered urinary metabolism and downregulated WISP1. The study supports the benefit of mechanical stimulations for locally and remotely suppressing tumor progression. It also indicated the role of WISP1 downregulation as a potential mechanism of loading-driven tumor suppression.

Loopy Lévy flights enhance tracer diffusion in active suspensions.

Brownian motion is widely used as a model of diffusion in equilibrium media throughout the physical, chemical and biological sciences. However, many real-world systems are intrinsically out of equilibrium owing to energy-dissipating active processes underlying their mechanical and dynamical features1. The diffusion process followed by a passive tracer in prototypical active media, such as suspensions of active colloids or swimming microorganisms2, differs considerably from Brownian motion, as revealed by a greatly enhanced diffusion coefficient3-10 and non-Gaussian statistics of the tracer displacements6,9,10. Although these characteristic features have been extensively observed experimentally, there is so far no comprehensive theory explaining how they emerge from the microscopic dynamics of the system. Here we develop a theoretical framework to model the hydrodynamic interactions between the tracer and the active swimmers, which shows that the tracer follows a non-Markovian coloured Poisson process that accounts for all empirical observations. The theory predicts a long-lived Lévy flight regime11 of the loopy tracer motion with a non-monotonic crossover between two different power-law exponents. The duration of this regime can be tuned by the swimmer density, suggesting that the optimal foraging strategy of swimming microorganisms might depend crucially on their density in order to exploit the Lévy flights of nutrients12. Our framework can be applied to address important theoretical questions, such as the thermodynamics of active systems13, and practical ones, such as the interaction of swimming microorganisms with nutrients and other small particles14 (for example, degraded plastic) and the design of artificial nanoscale machines15.

Expression of Glial Cell Line-derived Neurotrophic Factor in the Human Intervertebral Disc.

STUDY DESIGN: Biochemical and immunohistochemical analyses by the human intervertebral disc (IVD) cells and tissues. OBJECTIVE: To examine the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptors, GDNF family receptor (GFR) α1 and rearranged during transfection (RET) in the human IVD cells and the tissues with the early and advanced stages of degeneration. SUMMARY OF BACKGROUND DATA: The neurotrophin family, including nerve growth factor, has been reported to be expressed in the IVDs and plays a role in hyperalgesia and neuronal sensitization. Despite having properties similar to the nerve growth factor, the expression of GDNF in the IVD remains unknown. METHODS: Human IVD cells were cultured in monolayer. Immunohistochemical analyses and western blotting were performed to examine the protein levels of GDNF and its receptors. To examine the effect of proinflammatory cytokines, cells were cultured in the presence of interleukin-1ß (IL-1ß). The immunohistochemical expression of these proteins was also evaluated using human IVD tissues with different stages of degeneration. RESULTS: Immunofluorescent reactivity against anti-GDNF, GFRα1, and RET antibodies was identified in human IVD cells. In protein extracts from IVD cells, those protein expressions were also identified by Western blot. IL-1ß significantly stimulated the mRNA expression of GDNF compared with that of the control group. There was no significant effect of IL-1ß on the mRNA expression of GFRα1 and RET. The percentage of GDNF-immunopositive cells in advanced degenerated discs was significantly higher than that in early degenerated discs, whereas those of GFRα1 and RET showed no significant differences. CONCLUSIONS: GDNF and its receptors were constitutively expressed in the human IVD cells. GDNF expression was significantly enhanced by proinflammatory stimuli, and in the microenvironment with advanced tissue degeneration. LEVEL OF EVIDENCE: N/A.

A mathematical model explores the contributions of bending and stretching forces to shoot gravitropism in Arabidopsis.

Plant shoot gravitropism is a complex phenomenon resulting from gravity sensing, curvature sensing (proprioception), the ability to uphold self-weight and growth. Although recent data analysis and modelling have revealed the detailed morphology of shoot bending, the relative contribution of bending force (derived from the gravi-proprioceptive response) and stretching force (derived from shoot axial growth) behind gravitropism remains poorly understood. To address this gap, we combined morphological data with a theoretical model to analyze shoot bending in wild-type and lazy1-like 1 mutant Arabidopsis thaliana. Using data from actual bending events, we searched for model parameters that minimized discrepancies between the data and mathematical model. The resulting model suggests that both the bending force and the stretching force differ significantly between the wild type and mutant. We discuss the implications of the mechanical forces associated with differential cell growth and present a plausible mechanical explanation of shoot gravitropism.

Effects of Temperature and Humidity on the Skin Permeation of Hydrophilic and Hydrophobic Drugs.

The humidity was a well-known method to hydrate the skin; however, the published data were varied, and systemic experiments in the previous papers were few. Therefore, the in vitro permeation of excised porcine ear skin by drugs with different polarities [aminopyrine (AMP), antipyrine (ANP), methylparaben (MP), and ibuprofen (IP)] was analyzed under a constant skin surface temperature with different temperatures and humidities to reveal the effects of temperature and humidity on the skin permeation enhancement effects. Applied formulations were prepared by mixing the drug and a hydrophilic vehicle containing glycerin. The disposition-distance profiles of water and the humectant glycerin in the stratum corneum were also investigated using confocal Raman microscopy. High absolute humidity (AH) significantly contributed to the high skin penetration of the hydrophilic penetrants AMP, ANP, and MP but not the hydrophobic penetrant IP. An increase in the partition parameter and a decrease in the diffusivity parameter occurred with an increase in AH, independent of drug polarity. Moreover, we found that dew condensation induced by high AH on temperature-controlled skin surface may effectively increase water content and may provide higher glycerin distribution in the skin barrier, the stratum corneum. Increasing the amount of water and hydrophilic vehicles such as glycerin in the stratum corneum may enhance the permeation of hydrophilic penetrants AMP, ANP, and MP. These data suggested a dew condensation on the skin surface induced by high AH at a constant skin surface temperature would be important to enhance hydrophilic penetrants.

Expression of the RANK/RANKL/OPG system in the human intervertebral disc: implication for the pathogenesis of intervertebral disc degeneration.

BACKGROUND: The expression of the receptor activator of nuclear factor kappa B (RANK) /RANK ligand (RANKL) /osteoprotegerin (OPG) system and its association with the progression of intervertebral disc (IVD) degeneration has recently been reported in a human IVD. However, the effect of the RANK/RANKL/OPG system on the matrix metabolism of human IVD cells, especially on the expression of catabolic factors relevant to IVD degeneration, remains unknown. The purpose of this study was to examine the expression of the RANK/RANKL/OPG system, and then to evaluate the effect of this system on the expression of catabolic factors by human IVD cells. METHODS: Annulus fibrosus (AF) and nucleus pulposus (NP) cells isolated by sequential enzyme digestion from human IVD tissues obtained during spine surgeries were monolayer cultured. The expression of the RANK/RANKL/OPG system was determined using immunohistochemical methods and real-time polymerase chain reaction (PCR). To evaluate the influence of interleukin-1 beta (IL-1ß) stimulation on the mRNA expression of RANK, RANKL, and OPG, recombinant human IL-1ß (rhIL-1ß) was administered in the culture media of IVD cells. To examine the influence of RANKL signaling on the expression of matrix metalloprotease-3 (MMP-3), MMP-13, and IL-1ß, the cells were cultured with exogenous recombinant human RANKL (rhRANKL), recombinant human OPG (rhOPG) or anti-human RANKL mouse monoclonal antibody (ahRANKL-mAB) with or without rhIL-1ß. RESULTS: Immunoreactivity to RANK/RANKL/OPG and the mRNA expression of the three genes were obviously identified in both AF and NP cells. rhIL-1ß stimulation significantly upregulated the mRNA expression level of RANK/RANKL/OPG. The mRNA expression of catabolic factors was significantly upregulated by stimulation of rhRANKL in the presence of rhIL-1ß. On the other hand, the administration of either rhOPG or ahRANKL-mAB significantly suppressed the mRNA expression of catabolic factors that had been upregulated by rhIL-1ß stimulation. The suppressive effect of ahRANKL-mAB against rhIL-1ß stimulation was also confirmed by the protein expression of MMP-3. CONCLUSIONS: The present study showed that the RANK/RANKL/OPG system may be involved in the progression of IVD degeneration. This study also suggested the potential use of anti-RANKL monoclonal antibody and OPG as therapeutic agents to suppress the progression of IVD degeneration.

Twist-Induced Snapping in a Bent Elastic Rod and Ribbon.

Snapping of a slender structure is utilized in a wide range of natural and manmade systems, mostly to achieve rapid movement without relying on musclelike elements. Although several mechanisms for elastic energy storage and rapid release have been studied in detail, a general understanding of the approach to design such a kinetic system is a key challenge in mechanics. Here we study a twist-driven buckling and fast flip dynamics of a geometrically constrained ribbon by combining experiments, numerical simulations, and an analytical theory. We identify two distinct types of shape transitions: A narrow ribbon snaps, and a wide ribbon forms a pair of localized helices. We construct a phase diagram and explain the origin of the boundary, which is determined largely by the geometry. We quantify the effects of gravity and clarify the timescale dictating the rapid flipping. Our study reveals the unique role of geometric twist-bend coupling in the fast dynamics of a thin constrained structure, which has implications for a wide range of biophysical and applied physical problems.

Effect of layered application on the skin permeation of a cosmetic active component, rhododendrol.

Cosmetics containing rhododendrol (RD) were voluntarily recalled after incidents of leukoderma related to their use. Users reported using up to five different RD-containing products by layered application. In this study, we investigated the effects of layered application, formulations, and their components on the skin permeation of cosmetics containing RD. Experiments were designed to simulate actual in-use conditions, such as varying application volumes, physical mixing of formulations, sequence of cosmetics application and time interval between applications, to establish their effect on the skin permeation of RD. Milk and lotion RD-containing cosmetics (2%), 1% aqueous RD, and preparations of formulation components were applied as the first or second layers as finite doses of 10 or 20 µL/cm2. Permeation experiments were performed through excised porcine ear skin using Franz diffusion cells with an effective diffusion area of 1.77 cm2. Cosmetics applied by layered application exhibited lower skin permeation of RD compared with a single application despite having the same application dose. High initial volume (20 µL at 0 or 5 sec) did not exhibit any significant reduction in the permeation of RD. Formulations and their components caused varying reductions in RD permeation, probably due to changes in thermodynamic activity of the active component. Layered application, formulation components, application volume, time interval and sequence of application had significant influences on the skin permeation of the active component. Moreover, this study established a method of investigating the influence of formulations and their components on the skin permeation of actives after layered application.

Prediction of Skin Permeation of Flurbiprofen from Neat Ester Oils and Their O/W Emulsions.

Although many in silico models were reported to predict the skin permeation of drugs from aqueous solutions, few studies were founded on the in silico estimation models for the skin permeation of drugs from neat oil formulations and o/w emulsions. In the present study, the cumulative amount of a model lipophilic drug, flurbiprofen (FP), that permeated through skin was determined from 12 different kinds of ester oils (Qoil) and an in silico model was developed for predicting the skin permeation of FP from these ester oils. Thus, the obtained Qoil values were well predicted with the FP solubility in the oils (Soil), the amount of FP uptake into the stratum corneum (SCoil) and molecular descriptors of dipolarity/polarizability (π2H) and molecular density. This model suggests that the thermodynamic activities of FP both in the formulations and skin are the key factors for predicting the skin permeation of FP from the ester oils. In addition, a high linear relationship was observed in the double-logarithm plots between the Qoil and the cumulative amount of FP permeated through skin from 20% ester oil in water emulsion (Qemul20%). Furthermore, the skin permeations of FP from 5 and 10% ester oil in water emulsions, Qemul5% and Qemul10%, respectively, were also predicted by the horizontal translation of the y-axis intercept of the liner equation for the relation between the Qoil and Qemul20%. These prediction methods must be helpful for designing topical oily and/or o/w emulsion formulations having suitable and high skin permeation rate of lipophilic drugs.

Snap-buckling in asymmetrically constrained elastic strips.

When a flat elastic strip is compressed along its axis, it is bent in one of two possible directions via spontaneous symmetry breaking, forming a cylindrical arc. This is a phenomenon well known as Euler buckling. When this cylindrical section is pushed in the other direction, the bending direction can suddenly reverse. This instability is called "snap-through buckling" and is one of the elementary shape transitions in a prestressed thin structure. Combining experiments and theory, we study snap-buckling of an elastic strip with one end hinged and the other end clamped. These asymmetric boundary constraints break the intrinsic symmetry of the strip, generating mechanical behaviors, including largely hysteretic but reproducible force responses and switchlike discontinuous shape changes. We establish the set of exact analytical solutions to fully explain all our major experimental and numerical findings. Asymmetric boundary conditions arise naturally in diverse situations when a thin object is in contact with a solid surface at one end. The introduction of asymmetry through boundary conditions yields new insight into complex and programmable functionalities in material and industrial design.