Journal articles on the topic 'MSK Tissue Loading'

Human evolution required adaptation to the boundary conditions of Earth, including 1 g gravity. The bipedal mobility of Homo sapiens in that gravitational field causes ground reaction force (GRF) loading of their lower extremities, influencing the integrity of the tissues of those extremities. However, humans usually experience such loading during the day and then a period of relative unloading at night. Many studies have indicated that loading of tissues and cells of the musculoskeletal (MSK) system can inhibit their responses to biological mediators such as cytokines and growth factors. Such findings raise the possibility that humans use such cycles of acute conditioning and deconditioning of the cells and tissues of the MSK system to elaborate critical mediators and responsiveness in parallel with these cycles, particularly involving GRF loading. However, humans also experience circadian rhythms with the levels of a number of mediators influenced by day/night cycles, as well as various levels of biological clocks. Thus, if responsiveness to MSK-generated mediators also occurs during the unloaded part of the daily cycle, that response must be integrated with circadian variations as well. Furthermore, it is also possible that responsiveness to circadian rhythm mediators may be regulated by MSK tissue loading. This review will examine evidence for the above scenario and postulate how interactions could be both regulated and studied, and how extension of the acute cycles biased towards deconditioning could lead to loss of tissue integrity.

In this paper, the purpose is to compare three different cone fit of dental implant around the surrounding bone tissue that influence on fatigue and biomechanics, it is also to provide a theoretical basis for the design and clinical application of dental implant. The method is that loading the force 100N and 200N with different angle to the three different cone with dental implant with the finite element analysis (FEA) that analyzes the stress and fatigue in ideal conditions. The Results is that when the loading is vertical, cone for 3 degrees of the implant have the best performance. The cone for 80 degrees of the implant is min among the max equivalent stress of the implants. However, comprehensive view, Cone for 24 degrees of the implant the most stable. we find that cone of different implant when subjected to the same force the maximum equivalent stress is different, smaller conical implant under vertical load force have good performance, but with the increase of the loading angle the bigger conical implant performance better.

Transmural pressure at any level in the upper airway is dependent on the difference between intraluminal airway and extraluminal tissue pressure (ETP). We hypothesized that ETP would be influenced by topography, head and neck position, resistive loading, and stimulated breathing. Twenty-eight male, New Zealand White, anesthetized, spontaneously breathing rabbits breathed via a face mask with attached pneumotachograph to measure airflow and pressure transducer to monitor mask pressure. Tidal volume was measured via integration of the airflow signal. ETP was measured with a pressure transducer-tipped catheter inserted in the tissues of the lateral (ETPlat, n = 28) and anterior (ETPant, n = 21) pharyngeal wall. Head position was controlled at 30, 50, or 70°, and the effect of addition of an external resistor, brief occlusion, or stimulated breathing was examined. Mean ETPlat was ∼0.7 cmH2O greater than mean ETPant when adjusted for degree of head and neck flexion ( P < 0.05). Mean, maximum, and minimum ETP values increased significantly by 0.7-0.8 cmH2O/20° of head and neck flexion when adjusted for site of measurement ( P < 0.0001). The main effect of resistive loading and occlusion was an increase in the change in ETPlat (maximum - minimum ETPlat) and change in ETPant at all head and neck positions ( P < 0.05). Mean ETPlat and ETPant increased with increasing tidal volume at head and neck position of 30° (all P < 0.05). In conclusion, ETP was nonhomogeneously distributed around the upper airway and increased with both increasing head and neck flexion and increasing tidal volume. Brief airway occlusion increased the size of respiratory-related ETP fluctuations in upper airway ETP.

Bone microstructure is dominantly composed of anisotropic extracellular matrix (ECM) in which collagen fibers and epitaxially-oriented biological apatite (BAp) crystals are preferentially aligned depending on the bone anatomical position, resulting in exerting appropriate mechanical function. The regenerative bone in bony defects is however produced without the preferential alignment of collagen fibers and the c-axis of BAp crystals, and subsequently reproduced to recover toward intact alignment. Thus, it is necessary to produce the anisotropic bone-mimetic tissue for the quick recovery of original bone tissue and the related mechanical ability in the early stage of bone regeneration. Our group is focusing on the methodology for regulating the arrangement of bone cells, the following secretion of collagen and the self-assembled mineralization by oriented BAp crystallites. Cyclic stretching in vitro to bone cells, principal-stress loading in vivo on scaffolds, step formation by slip traces on Ti single crystal, surface modification by laser induced periodic surface structure (LIPSS), anisotropic collagen substrate with the different degree of orientation, etc. can dominate bone cell arrangement and lead to the construction of the oriented ECM similar to the bone tissue architecture. This suggests that stress/strain loading, surface topography and chemical anisotropy are useful to produce bone-like microstructure in order to promote the regeneration of anisotropic bone tissue and to understand the controlling parameters for anisotropic osteogenesis induction.

It is of great interest in tissue engineering the role of collagen gel-based structures (scaffolds, grafts and-by cell seeded and maturation-tissue equivalents (TEs) for several purposes). It is expected the appropriate biological compatibility when the extracellular matrix (ECM) is collagen-based. Regarding the mechanical properties (MP), great efforts in tissue engineering are focused in tailoring TE properties by controlling ECM composition and organization. When cells are seeded, the collagen network is remodeled by cell-driven compaction and consolidation, produced mainly through the mechanical stimuli that can be directed selecting the geometry and the surfaces exposed to the cells. Collagen gels have different (chemical and mechanical) properties depending on their origin and preparation conditions. The MP of the collagen network are derived from the degree of cross-linking (CLD) which can be modified by different treatments. One of the techniques to evaluate MP in the network is by ultrasound (US). In this work we analyse the effect of several mechanical constraints (similar to that imposed to promote cell growth on certain sample surfaces, when seeded) on samples of gelatin with a specific geometry (thick walls cylinders) under loading conditions of pulsatile flow. We checked US parameters and estimates evolution of the network structure for different restrictions in the sample mobility. It was implemented by adapting devices specially built to measure elastic properties of biological tissues by US. The material (origin and purity) and the preparation conditions for the gelatin were selected in order to compare the results with those of literature.

In mammals, phosphate balance is maintained by influx and efflux via the intestines, kidneys, bone, and soft tissue, which involves multiple sodium/phosphate (Na+/Pi) cotransporters, as well as regulation by several hormones. Alterations in the levels of extracellular phosphate exert effects on both skeletal and extra-skeletal tissues, and accumulating evidence has suggested that phosphate itself evokes signal transduction to regulate gene expression and cell behavior. Several in vitro studies have demonstrated that an elevation in extracellular Piactivates fibroblast growth factor receptor, Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular signal-regulated kinase) pathway and Akt pathway, which might involve the type III Na+/Picotransporter PiT-1. Excessive phosphate loading can lead to various harmful effects by accelerating ectopic calcification, enhancing oxidative stress, and dysregulating signal transduction. The responsiveness of mammalian cells to altered extracellular phosphate levels suggests that they may sense and adapt to phosphate availability, although the precise mechanism for phosphate sensing in mammals remains unclear. Unicellular organisms, such as bacteria and yeast, use some types of Pitransporters and other molecules, such as kinases, to sense the environmental Piavailability. Multicellular animals may need to integrate signals from various organs to sense the phosphate levels as a whole organism, similarly to higher plants. Clarification of the phosphate-sensing mechanism in humans may lead to the development of new therapeutic strategies to prevent and treat diseases caused by phosphate imbalance.

Fractures resulting from wear and fatigue process have been identified as the main causes of failure in biomaterials, especially in implants that act in place of bone or other hard tissue, as they are subject to conditions involving severe cyclic loadings. In biomaterialscase, the types of failures mentioned above must also be evaluated under the effect of degradation or corrosion, due to the direct contact with body fluids. The present research analyzed the fatigue induced by corrosion fracture of an orthopaedic implant for total knee replacementproduced with an austenitic ASTM F138 stainless steel. The morphology, compositions of the interfaces and subsequent corrosive pitting were characterized by stereoscopy and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Stress concentration, inclusions and high carbon levels were the main reasons of failure.

Nanostructured titanium (nTi) with essential enhanced strength and fatigue characteristics is an advanced material for dental implant applications. Nano Ti is commercially pure titanium, that was nanostructured by a special technique of severe plastic deformation. It is bio inert, does not contain even potentially toxic or allergenetic additives and has significantly higher specific strength properties than any other titanium applied in dental implants. Cylindrical threaded screw implants Nanoimplant® sized 2.4 mm in diameter and 12 mm in length were made from nTi. It is the first application of nTi dental implant in the world reported. Recently more than 250 successful clinical applications dealing with surgery on the front teeth were carried out. No complications were noticed during the early postoperative period and early loading. Laboratory cytocompatibility tests undertaken so far on mice fibroblast cells have indicated that nanocrystalline Ti surface has a significantly better property for cell colonisation and healing of tissue consequently.

The Ti-21.8Nb-6Zr and Ti-19.7Nb-5.8Ta (at.%) shape memory alloys are thermomechanically treated by cold drawing and post-deformation annealing at 550-600°C forming a nanosubgrained structure in the β-phase. Cyclic mechanical testing using a “loading-unloading” mode with 2% tensile strain in each half-cycle reveals the non-perfect superelastic behavior of both alloys during the very first cycles of testing, which becomes perfect during further mechanocycling. The Young’s modulus of thermomechanically-treated alloys is low (about 45 GPa), and it decreases during mechanocycling (n=10 cycles) down to 25-35 GPa, approaching the Young’s modulus of cortical bone tissues. The Young’s modulus obtained in the 10th cycle is stable or changes only slightly during a further 40-day pause at room temperature and then during repeated mechanocycling. The residual strain per cycle, the transformation yield stress and the mechanical hysteresis decrease during mechanocycling. Subsequent to a 40-day pause at room temperature, they restore their initial values. Repeated mechanocycling is accompanied by a repeated decrease of these parameters.

Pancreatic stellate cells (PSCs) play a central role in development of pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of the normal pancreas. We here evaluate the effects of pressure on the activation of rat PSCs. PSCs were isolated from the pancreas of Wistar rat using collagenase digestion and centrifugation with Nycodenz gradient. Pressure was applied to cultured rat PSCs by adding compressed helium gas into the pressure-loading apparatus to raise the internal pressure. Cell proliferation rate was assessed by 5-bromo-2′-deoxyuridine (BrdU) incorporation. MAPK protein levels and α-smooth muscle actin (α-SMA) expression were evaluated by Western blot analysis. Concentration of activated transforming growth factor-β1 (TGF-β1) secreted from PSCs into culture medium was determined by ELISA. Collagen type I mRNA expression and collagen secretion were assessed by quantitative PCR and Sirius red dye binding assay, respectively. Application of pressure significantly increased BrdU incorporation and α-SMA expression. In addition, pressure rapidly increased the phosphorylation of p44/42 and p38 MAPK. Treatment of PSCs with an MEK inhibitor and p38 MAPK inhibitor suppressed pressure-induced cell proliferation and α-SMA expression, respectively. Moreover, pressure significantly promoted activated TGF-β1 secretion, collagen type I mRNA expression, and collagen secretion. Our results demonstrate that pressure itself activates rat PSCs and suggest that increased pancreatic tissue pressure may accelerate the development of pancreatic fibrosis in chronic pancreatitis.

As an initial step of this research, open cell magnesium foams were obtained by infiltration casting using a preform of salt particles with irregular morphology. Despite this metallic foam was a successful approach to bone replacement scaffold, the properties of a metal foam need to be improved to meet the requirements by accurately adjusting the porous geometry. The tissue scaffold structure should be submissive biologically as well as mechanically and should at best mimic the natural properties of bone to act as an accurate bone substitute. The architectural and mechanical bone scaffold parameters determine the biological outcome.This work aims to design and manufacture an ordered foam with mechanical and architectural properties similar to those of the bone using an Mg alloy as a base material. Accordingly, representative features were identified to generate computer-aided designed (CAD) unit cells. Then, a set of the selected cells was assembled to obtain a specified architecture for bone replacement. Finite element method analysis was applied to calculate the mechanical response. The architectural parameters were varied to match the elastic properties of human bone concerning suitable exposed area, volume, and pore size. The best architecture was determined by compression loading acting on the assembly. Finally, polymeric stamps with sets of truncated octahedrons will be printed from the CAD model and were replicated in a clay made with a combination of salt and flour. Infiltration casting will obtain last of all, open cell magnesium foams.

A long-standing challenge in the biomechanics of connective tissues (e.g., articular cartilage, ligament, tendon) has been the reported disparities between their tensile and compressive properties. In general, the intrinsic tensile properties of the solid matrices of these tissues are dictated by the collagen content and microstructural architecture, and the intrinsic compressive properties are dictated by their proteoglycan content and molecular organization as well as water content. These distinct materials give rise to a pronounced and experimentally well-documented nonlinear tension–compression stress–strain responses, as well as biphasic or intrinsic extracellular matrix viscoelastic responses. While many constitutive models of articular cartilage have captured one or more of these experimental responses, no single constitutive law has successfully described the uniaxial tensile and compressive responses of cartilage within the same framework. The objective of this study was to combine two previously proposed extensions of the biphasic theory of Mow et al. [1980, ASME J. Biomech. Eng., 102, pp. 73–84] to incorporate tension–compression nonlinearity as well as intrinsic viscoelasticity of the solid matrix of cartilage. The biphasic-conewise linear elastic model proposed by Soltz and Ateshian [2000, ASME J. Biomech. Eng., 122, pp. 576–586] and based on the bimodular stress-strain constitutive law introduced by Curnier et al. [1995, J. Elasticity, 37, pp. 1–38], as well as the biphasic poroviscoelastic model of Mak [1986, ASME J. Biomech. Eng., 108, pp. 123–130], which employs the quasi-linear viscoelastic model of Fung [1981, Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York], were combined in a single model to analyze the response of cartilage to standard testing configurations. Results were compared to experimental data from the literature and it was found that a simultaneous prediction of compression and tension experiments of articular cartilage, under stress-relaxation and dynamic loading, can be achieved when properly taking into account both flow-dependent and flow-independent viscoelasticity effects, as well as tension–compression nonlinearity.

Resume. According to epidemiological studies, there is still an increased prevalence of periodontal disease among the population of different regions of the world, with increasing intensity and aggressiveness. Long-term chronic generalized lesions of recurrent and progressive inflammatory-dystrophic process lead to the destruction of alveolar processes, pathological mobility of teeth, tooth loss and dentofacial dysfunctions. One of the most characteristic symptoms of generalized periodontitis is the presence of traumatic occlusion. Depending on the degree of pathological changes in periodontal tissues, the size and topography of dentition defects, the replacement of dentition pathologies should be planned by splint-type orthopedic structures and computerized analysis of occlusal relationships with T-Scan III system. The aim of the study is to improve the effectiveness of orthopedic treatment of periodontal diseases complicated by defects of the dentition with the control of occlusal relationships with a computerized T-Scan III system. Materials and methods. We have examined 87 persons aged between 30 and 69 years with generalized periodontitis of I – III severity, complicated by partial loss of teeth of different sizes and topography, and a control group of the same age in 10 patients with intact dentition and physiological forms of occlusion without clinically diagnosed periodontal diseases. Computerized analysis of occlusion indices was performed by the T-Scan III system. We have investigated the stereotype of functional loads according to the following quantitative and qualitative indicators: the index of asymmetry of force between the parts (%); time of occurrence of the maximum amount of dental contacts (sec); time of disclusion (sec); the presence of premature occlusal contacts on the natural teeth and orthopedic constructions, and the presence of changes in the direction of the trajectory of the total vector of occlusal load. Orthopedic rehabilitation of patients in the case of periodontal diseases of the I-II degree of severity and the presence of small defects of the dentition, we conducted by splint-type orthopedic structures, dental implants, and artificial crowns of our own design with discrete occlusal loading (Licence for Effective Model No 143278, Ukraine, MPK А61С 13/007, u 2019 11487: Artificial Crown with Support on a Dental Implant). Patients with periodontal diseases of the II – III severity, complicated by defects of dentitions with different size and topography, the dental prosthetics has been performed by traditional removable and combined orthopedic splint-type constructions, and removable splint-type dentures of their own design: "Removable Prosthesis of Splint Type" (Licence for Effective Model No 130980 Ukraine, IPC (2006.01) А61С 13/007, u 2018 03039, 10.01.2019). Computerized analysis of occlusion indicators for the patients of I and II clinical groups and the III control group has been performed before and after orthopedic treatment by T-Scan III system. Results of the research. The results of investigation for functional occlusion have demonstrated that the index of relative strength asymmetry between the sides of the dentition in patients with generalized periodontitis complicated by dentition defects increased significantly and led to nonphysiological redistribution of loads compared with indices obtained in patients from control group due to the lack of correspondence for occlusal contacts. These indices are equal to 16.7 ± 3.8% in patients of I group and 18.9 ± 4.8% in group II compared to the similar control indicators – 4.7 ± 1.01%, respectively (p≤0.01). It should be noted that these indicators have differed from the control group indicators according to the severity of the pathological process. Rational prosthetics with removable and non-removable orthopedic structures, including on the base of dental implants, helps to optimize occlusal relations. Conclusions. Occlusographic studies performed in patients with generalized periodontitis having different severity and complicated by partial tooth loss have showed increased index of relative strength asymmetry between the sides of chewing, the presence of premature contacts and incorrect location of the trajectory of the total occlusal load vector. The dynamics of pathological changes in occlusion indices corresponds to the degree of generalized periodontitis, which indicates the necessity of opportune replacement of dentition defects, taking into account the occlusal relations. Rational prosthetics helps to optimize occlusal relations.

Hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days. Equal amounts of proteins from urinary bladder or liver extracts of control and arsenic-treated hamsters were labeled with Cy3 and Cy5 dyes, respectively. After differential in gel electrophoresis and analysis by the DeCyder software, several protein spots were found to be down-regulated and several were up regulated. Our experiments indicated that in the bladder tissues of hamsters exposed to arsenite, transgelin was down-regulated and GST-pi was up-regulated. The loss of transgelin expression has been reported to be an important early event in tumor progression and a diagnostic marker for cancer development [29-32]. Down-regulation of transgelin expression may be associated with the carcinogenicity of inorganic arsenic in the urinary bladder. In the liver of arsenite-treated hamsters, ornithine aminotransferase was up-regulated, and senescence marker protein 30 and fatty acid binding protein were down-regulated. The volume ratio changes of these proteins in the bladder and liver of hamsters exposed to arsenite were significantly different than that of control hamsters. Introduction Chronic exposure to inorganic arsenic can cause cancer of the skin, lungs, urinary bladder, kidneys, and liver [1-6]. The molecular mechanisms of the carcinogenicity and toxicity of inorganic arsenic are not well understood [7-9). Humans chronically exposed to inorganic arsenic excrete MMA(V), DMA(V) and the more toxic +3 oxidation state arsenic biotransformants MMA(III) and DMA (III) in their urine [10, 11], which are carcinogen [12]· After injection of mice with sodium arsenate, the highest concentrations of the very toxic MMA(III) and DMA(III) were in the kidneys and urinary bladder tissue, respectively, as shown by experiments of Chowdhury et al [13]. Many mechanisms of arsenic toxicity and carcinogenicity have been suggested [1, 7, 14] including chromosome abnormalities [15], oxidative stress [16, 17], altered growth factors [18], cell proliferation [19], altered DNA repair [20], altered DNA methylation patterns [21], inhibition of several key enzymes [22], gene amplification [23] etc. Some of these mechanisms result in alterations in protein expression. Methods for analyzing multiple proteins have advanced greatly in the last several years. In particularly, mass spectrometry (MS) and tandem MS (MS/MS) are used to analyze peptides following protein isolation using two-dimensional (2-D) gel electrophoresis and proteolytic digestion [24]. In the present study, Differential In Gel Electrophoresis (DIGE) coupled with Mass Spectrometry (MS) has been used to study some of the proteomic changes in the urinary bladder and liver of hamsters exposed to sodium arsenite in their drinking water. Our results indicated that transgelin was down-regulated and GST-pi was up-regulated in the bladder tissues. In the liver tissues ornithine aminotransferase was up-regulated, and senescence marker protein 30, and fatty acid binding protein were down-regulated. Materials and Methods Chemicals Tris, Urea, IPG strips, IPG buffer, CHAPS, Dry Strip Cover Fluid, Bind Silane, lodoacetamide, Cy3 and Cy5 were from GE Healthcare (formally known as Amersham Biosciences, Uppsala, Sweden). Thiourea, glycerol, SDS, DTT, and APS were from Sigma-Aldrich (St. Louis, MO, USA). Glycine was from USB (Cleveland, OH, USA). Acrylamide Bis 40% was from Bio-Rad (Hercules, CA, USA). All other chemicals and biochemicals used were of analytical grade. All solutions were made with Milli-Q water. Animals Male hamsters (Golden Syrian), 4 weeks of age, were purchased from Harlan Sprague Dawley, USA. Upon arrival, hamsters were acclimated in the University of Arizona animal care facility for at least 1 week and maintained in an environmentally controlled animal facility operating on a 12-h dark/12-h light cycle and at 22-24°C. They were provided with Teklad (Indianapolis, IN) 4% Mouse/Rat Diet # 7001 and water, ad libitum, throughout the acclimation and experimentation periods. Sample preparation and labelling Hamsters were exposed to sodium arsenite (173 mg) in drinking water for 6 days and the control hamsters were given tap water. On the 6th day hamsters were decapitated rapidly by guillotine. Urinary bladder tissues and liver were removed, blotted on tissue papers (Kimtech Science, Precision Wipes), and weighed. Hamster urinary bladder or liver tissues were homogenized in lysis buffer (30mMTris, 2M thiourea, 7M urea, and 4% w/w CHAPS adjusted to pH 8.5 with dilute HCI), at 4°C using a glass homogenizer and a Teflon coated steel pestle; transferred to a 5 ml acid-washed polypropylene tube, placed on ice and sonicated 3 times for 15 seconds. The sonicate was centrifuged at 12,000 rpm for 10 minutes at 4°C. Small aliquots of the supernatants were stored at -80°C until use (generally within one week). Protein concentration was determined by the method of Bradford [25] using bovine serum albumin as a standard. Fifty micrograms of lysate protein was labeled with 400 pmol of Cy3 Dye (for control homogenate sample) and Cy5 Dye (for arsenic-treated urinary bladder or liver homogenate sample). The samples containing proteins and dyes were incubated for 30 min on ice in the dark. To stop the labeling reaction, 1uL of 10 mM lysine was added followed by incubation for 10 min on ice in the dark. To each of the appropriate dye-labeled protein samples, an additional 200 ug of urinary bladderor liver unlabeled protein from control hamster sample or arsenic-treated hamster sample was added to the appropriate sample. Differentially labeled samples were combined into a single Microfuge tube (total protein 500 ug); protein was mixed with an equal volume of 2x sample buffer [2M thiourea, 7M urea, pH 3-10 pharmalyte for isoelectric focusing 2% (v/v), DTT 2% (w/v), CHAPS 4% (w/v)]; and was incubated on ice in the dark for 10 min. The combined samples containing 500 ug of total protein were mixed with rehydration buffer [CHAPS 4% (w/v), 8M urea, 13mM DTT, IPG buffer (3-10) 1% (v/v) and trace amount of bromophenol blue]. The 450 ul sample containing rehydration buffer was slowly pipetted into the slot of the ImmobilinedryStripReswelling Tray and any large bubbles were removed. The IPG strip (linear pH 3-10, 24 cm) was placed (gel side down) into the slot, covered with drystrip cover fluid (Fig. 1), and the lid of the Reswelling Tray was closed. The ImmobillineDryStrip was allowed to rehydrate at room temperature for 24 hours. First dimension Isoelectric focusing (IEF) The labeled sample was loaded using the cup loading method on universal strip holder. IEF was then carried out on EttanIPGphor II using multistep protocol (6 hr @ 500 V, 6 hr @ 1000 V, 8 hr @ 8000 V). The focused IPG strip was equilibrated in two steps (reduction and alkylation) by equilibrating the strip for 10 min first in 10 ml of 50mM Tris (pH 8.8), 6M urea, 30% (v/v) glycerol, 2% (w/v) SDS, and 0.5% (w/v) DTT, followed by another 10 min in 10 ml of 50mM Tris (pH 8.8), 6M urea, 30% (v/v) glycerol, 2% (w/v) SDS, and 4.5% (w/v) iodoacetamide to prepare it for the second dimension electrophoresis. Second dimension SDS-PAGE The equilibrated IPG strip was used for protein separation by 2D-gel electrophoresis (DIGE). The strip was sealed at the top of the acrylamide gel for the second dimension (vertical) (12.5% polyacrylamide gel, 20x25 cm x 1.5 mm) with 0.5% (w/v) agarose in SDS running buffer [25 mMTris, 192 mM Glycine, and 0.1% (w/v) SDS]. Electrophoresis was performed in an Ettan DALT six electrophoresis unit (Amersham Biosciences) at 1.5 watts per gel, until the tracking dye reached the anodic end of the gel. Image analysis and post-staining The gel then was imaged directly between glass plates on the Typhoon 9410 variable mode imager (Sunnyvale, CA, USA) using optimal excitation/emission wavelength for each DIGE fluor: Cy3 (532/580 nm) and Cy5 (633/670 nm). The DIGE images were previewed and checked with Image Quant software (GE Healthcare) where all the two separate gel images could be viewed as a single gel image. DeCyde v.5.02 was used to analyze the DIGE images as described in the Ettan DIGE User Manual (GE Healthcare). The appropriate up-/down regulated spots were filtered based on an average volume ratio of ± over 1.2 fold. After image acquisition, the gel was fixed overnight in a solution containing 40% ethanol and 10% acetic acid. The fixed gel was stained with SyproRuby (BioRad) according to the manufacturer protocol (Bio-Rad Labs., 2000 Alfred Nobel Drive, Hercules, CA 94547). Identification of proteins by MS Protein spot picking and digestion Sypro Ruby stained gels were imaged using an Investigator ProPic and HT Analyzer software, both from Genomic Solutions (Ann Arbor, MI). Protein spots of interest that matched those imaged using the DIGE Cy3/Cy5 labels were picked robotically, digested using trypsin as described previously [24] and saved for mass spectrometry identification. Liquid chromatography (LC)- MS/MS analysis LC-MS/MS analyses were carried out using a 3D quadrupole ion trap massspectrometer (ThermoFinnigan LCQ DECA XP PLUS; ThermoFinnigan, San Jose, CA) equipped with a Michrom Paradigm MS4 HPLC (MichromBiosources, Auburn, CA) and a nanospray source, or with a linear quadrupole ion trap mass spectrometer (ThermoFinnigan LTQ), also equipped with a Michrom MS4 HPLC and a nanospray source. Peptides were eluted from a 15 cm pulled tip capillary column (100 um I.D. x 360 um O.D.; 3-5 um tip opening) packed with 7 cm Vydac C18 (Vydac, Hesperia, CA) material (5 µm, 300 Å pore size), using a gradient of 0-65% solvent B (98% methanol/2% water/0.5% formic acid/0.01% triflouroacetic acid) over a 60 min period at a flow rate of 350 nL/min. The ESI positive mode spray voltage was set at 1.6 kV, and the capillary temperature was set at 200°C. Dependent data scanning was performed by the Xcalibur v 1.3 software on the LCQ DECA XP+ or v 1.4 on the LTQ [27], with a default charge of 2, an isolation width of 1.5 amu, an activation amplitude of 35%, activation time of 50 msec, and a minimal signal of 10,000 ion counts (100 ion counts on the LTQ). Global dependent data settings were as follows: reject mass width of 1.5 amu, dynamic exclusion enabled, exclusion mass width of 1.5 amu, repeat count of 1, repeat duration of a min, and exclusion duration of 5 min. Scan event series were included one full scan with mass range of 350-2000 Da, followed by 3 dependent MS/MS scans of the most intense ion. Database searching Tandem MS spectra of peptides were analyzed with Turbo SEQUEST, version 3.1 (ThermoFinnigan), a program that allows the correlation of experimental tandem MS data with theoretical spectra generated from known protein sequences. All spectra were searched against the latest version of the non redundant protein database from the National Center for Biotechnology Information (NCBI 2006; at that time, the database contained 3,783,042 entries). Statistical analysis The means and standard error were calculated. The Student's t-test was used to analyze the significance of the difference between the control and arsenite exposed hamsters. P values less than 0.05 were considered significant. The reproducibility was confirmed in separate experiments. Results Analysis of proteins expression After DIGE (Fig. 1), the gel was scanned by a Typhoon Scanner and the relative amount of protein from sample 1 (treated hamster) as compared to sample 2 (control hamster) was determined (Figs. 2, 3). A green spot indicates that the amount of protein from sodium arsenite-treated hamster sample was less than that of the control sample. A red spot indicates that the amount of protein from the sodium arsenite-treated hamster sample was greater than that of the control sample. A yellow spot indicates sodium arsenite-treated hamster and control hamster each had the same amount of that protein. Several protein spots were up-regulated (red) or down-regulated (green) in the urinary bladder samples of hamsters exposed to sodium arsenite (173 mg As/L) for 6 days as compared with the urinary bladder of controls (Fig. 2). In the case of liver, several protein spots were also over-expressed (red) or under-expressed (green) for hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days (Fig. 3). The urinary bladder samples were collected from the first and second experiments in which hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days and the controls were given tap water. The urinary bladder samples from the 1st and 2nd experiments were run 5 times in DIGE gels on different days. The protein expression is shown in Figure 2 and Table 1. The liver samples from the 1st and 2nd experiments were also run 3 times in DIGE gels on different days. The proteins expression were shown in Figure 3 and Table 2. The volume ratio changed of the protein spots in the urinary bladder and liver of hamsters exposed to arsenite were significantly differences than that of the control hamsters (Table 1 and 2). Protein spots identified by LC-MS/MS Bladder The spots of interest were removed from the gel, digested, and their identities were determined by LC-MS/MS (Fig. 2 and Table 1). The spots 1, 2, & 3 from the gel were analyzed and were repeated for the confirmation of the results (experiments; 173 mg As/L). The proteins for the spots 1, 2, and 3 were identified as transgelin, transgelin, and glutathione S-transferase Pi, respectively (Fig. 2). Liver We also identified some of the proteins in the liver samples of hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days (Fig. 3). The spots 4, 5, & 6 from the gels were analyzed and were repeated for the confirmation of the results. The proteins for the spots 4, 5, and 6 were identified as ornithine aminotransferase, senescence marker protein 30, and fatty acid binding protein, respectively (Fig. 3) Discussion The identification and functional assignment of proteins is helpful for understanding the molecular events involved in disease. Weexposed hamsters to sodium arsenite in drinking water. Controls were given tap water. DIGE coupled with LC-MS/MS was then used to study the proteomic change in arsenite-exposed hamsters. After electrophoresis DeCyder software indicated that several protein spots were down-regulated (green) and several were up-regulated (red). Our overall results as to changes and functions of the proteins we have studied are summarized in Table 3. Bladder In the case of the urinary bladder tissue of hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days, transgelin was down-regulated and GST-pi was up-regulated. This is the first evidence that transgelin is down-regulated in the bladders of animals exposed to sodium arsenite. Transgelin, which is identical to SM22 or WS3-10, is an actin cross linking/gelling protein found in fibroblasts and smooth muscle [28, 29]. It has been suggested that the loss of transgelin expression may be an important early event in tumor progression and a diagnostic marker for cancer development [30-33]. It may function as a tumor suppressor via inhibition of ARA54 (co-regulator of androgen receptor)-enhanced AR (androgen receptor) function. Loss of transgelin and its suppressor function in prostate cancer might contribute to the progression of prostate cancer [30]. Down-regulation of transgelin occurs in the urinary bladders of rats having bladder outlet obstruction [32]. Ras-dependent and Ras-independent mechanisms can cause the down regulation of transgelin in human breast and colon carcinoma cell lines and patient-derived tumorsamples [33]. Transgelin plays a role in contractility, possibly by affecting the actin content of filaments [34]. In our experiments loss of transgelin expression may be associated or preliminary to bladder cancer due to arsenic exposure. Arsenite is a carcinogen [1]. In our experiments, LC-MS/MS analysis showed that two spots (1 and 2) represent transgelin (Fig. 2 and Table 1). In human colonic neoplasms there is a loss of transgelin expression and the appearance of transgelin isoforms (31). GST-pi protein was up-regulated in the bladders of the hamsters exposed to sodium arsenite. GSTs are a large family of multifunctional enzymes involved in the phase II detoxification of foreign compounds [35]. The most abundant GSTS are the classes alpha, mu, and pi classes [36]. They participate in protection against oxidative stress [37]. GST-omega has arsenic reductase activity [38]. Over-expression of GST-pi has been found in colon cancer tissues [39]. Strong expression of GST-pi also has been found in gastric cancer [40], malignant melanoma [41], lung cancer [42], breast cancer [43] and a range of other human tumors [44]. GST-pi has been up-regulated in transitional cell carcinoma of human urinary bladder [45]. Up-regulation of glutathione – related genes and enzyme activities has been found in cultured human cells by sub lethal concentration of inorganic arsenic [46]. There is evidence that arsenic induces DNA damage via the production of ROS (reactive oxygen species) [47]. GST-pi may be over-expressed in the urinary bladder to protect cells against arsenic-induced oxidative stress. Liver In the livers of hamsters exposed to sodium arsenite, ornithine amino transferase was over-expressed, senescence marker protein 30 was under-expressed, and fatty acid binding protein was under-expressed. Ornithine amino transferase has been found in the mitochondria of many different mammalian tissues, especially liver, kidney, and small intestine [48]. Ornithine amino transferase knockdown inhuman cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death [49]. It has been suggested that ornithine amino transferase has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cells [49]. Senescence marker protein-30 (SMP30) is a unique enzyme that hydrolyzes diisopropylphosphorofluoridate. SMP30, which is expressed mostly in the liver, protects cells against various injuries by stimulating membrane calcium-pump activity [50]. SMP30 acts to protect cells from apoptosis [51]. In addition it protects the liver from toxic agents [52]. The livers of SMP30 knockout mice accumulate phosphatidylethanolamine, cardiolipin, phosphatidyl-choline, phosphatidylserine, and sphingomyelin [53]. Liver fatty acid binding protein (L-FABP) also was down- regulated. Decreased liver fatty acid-binding capacity and altered liver lipid distribution hasbeen reported in mice lacking the L-FABP gene [54]. High levels of saturated, branched-chain fatty acids are deleterious to cells and animals, resulting in lipid accumulation and cytotoxicity. The expression of fatty acid binding proteins (including L-FABP) protected cells against branched-chain saturated fatty acid toxicity [55]. Limitations: we preferred to study the pronounced spots seen in DIGE gels. Other spots were visible but not as pronounced. Because of limited funds, we did not identify these others protein spots. In conclusion, urinary bladders of hamsters exposed to sodium arsenite had a decrease in the expression of transgelin and an increase in the expression of GST-pi protein. Under-expression of transgelin has been found in various cancer systems and may be associated with arsenic carcinogenicity [30-33). Inorganic arsenic exposure has resulted in bladder cancer as has been reported in the past [1]. Over-expression of GST-pi may protect cells against oxidative stress caused by arsenite. In the liver OAT was up regulated and SMP-30 and FABP were down regulated. These proteomic results may be of help to investigators studying arsenic carcinogenicity. The Superfund Basic Research Program NIEHS Grant Number ES 04940 from the National Institute of Environmental Health Sciences supported this work. Additional support for the mass spectrometry analyses was provided by grants from NIWHS ES06694, NCI CA023074 and the BIOS Institute of the University of Arizona. Acknowledgement The Author wants to dedicate this paper to the memory of his former supervisor Dr. H. VaskenAposhian who passed away in September 6, 2019. He was an emeritus professor of the Department of Molecular and Cellular Biology at the University of Arizona. 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Pregnancy is characterized by hormone changes that could alter musculoskeletal (MSK) properties and temporarily increase soft tissue injury risk. Whilst the prevalence of MSK injuries in pregnancy has not yet proven itself to be a widespread problem, indirect evidence indicates an uptake in the prevalence of strength training and vigorous-intensity activity during pregnancy, which may result in increased MSK injury incidence. Combining this evidence with the association between sex hormones and MSK injury risk, we recognize the potential importance of this research area and believe the (prospective) examination of connective tissue properties in relation to hormonal changes in pregnancy are appropriate. Given the dearth of information on MSK adaptations to pregnancy, we present a variety of morphological, mechanical and functional tendon data from two consecutive pregnancies in one woman as a means of highlighting this under-researched topic. This data may be representative of the general pregnant population, or it may be highly individualized - more research is required for a better understanding of MSK adaptation and injury risk during and after pregnancy.

Objective Ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences have improved imaging of short T2 musculoskeletal (MSK) tissues. UTE-MRI combined with magnetization transfer modeling (UTE-MT) has demonstrated robust assessment of MSK tissues. This study aimed to investigate the variation of UTE-MT measures under mechanical loading in tibiofemoral cartilage and meniscus of cadaveric knee joints. Design Fourteen knee joints from young ( n = 8, 42 ± 12 years old) and elderly ( n = 6, 89 ± 4 years old) donors were scanned on a 3-T scanner under 3 loading conditions: load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-MT sequences were performed at each loading condition. Macromolecular proton fraction (MMF) was calculated from UTE-MT modeling. Wilcoxon rank sum test was used to examine the MRI data differences between loading conditions. Results For young donors, MMF increased in all grouped regions of interest (meniscus [M], femoral articular cartilage [FAC], tibial articular cartilage [TAC], articular cartilage regions covered by meniscus [AC-MC], and articular cartilage regions uncovered by meniscus [AC-UC]) when the load increased from 300 to 500 N. The increases in MMF were significant for M (13.3%, P < 0.01) and AC-MC (9.2%, P = 0.04). MMF decreased in all studied regions after unloading, which was significant only for AC-MC (−8.9%, P = 0.01). For elderly donors, MRI parameters did not show significant changes by loading or unloading. Conclusion This study highlights the potential of the UTE-MT modeling combined with knee loading in differentiating between normal and abnormal knees. Average tissue deformation effects were likely higher and more uniformly distributed in the joints of young donors compared with elderly donors.

AbstractFor more than 20 years, robotic bioreactor systems have facilitated the growth of tissue-engineered constructs using mechanical stimulation. However, we are still unable to produce functional grafts that can translate into clinical use. Humanoid robots offer the prospect of providing physiologically-relevant mechanical stimulation to grafts and implants which may expedite their clinical deployment. To investigate the feasibility of a humanoid bioreactor, we have designed a flexible bioreactor chamber that can be attached to a modified musculoskeletal (MSK) humanoid robot shoulder joint. We demonstrate that fibroblast cells can be grown in this chamber while undergoing physiological adduction-abduction on the robotic arm. A preliminary evaluation of the transcriptome of the cells after 14 days indicated a clear influence of the loading regime on the gene expression profile. These early results will facilitate the exploration of MSK humanoid robots as a biomechanically more realistic platform for tissue engineering and biomaterial testing applications.

Concussions are among the most common injuries sustained by goaltenders. Concussive injuries are characterized by impairment to neurological function which can affect many different brain regions. Understanding how different impact loading conditions (event type and impact site) affect the brain tissue response may help identify what kind of impacts create a high risk of injury to specific brain regions. The purpose of this study was to examine the influence of different impact conditions on the distribution of brain strain for ice hockey goaltender impacts. An instrumented headform was fitted with an ice hockey goaltender mask and impacted under a protocol which was developed using video analysis of real world ice hockey goaltender concussions for three different impact events (collision, puck, and fall). The resulting kinematic response served as input into the University College Dublin Brain Trauma Model (UCDBTM), which calculated maximum principal strain (MPS) in the cerebrum. Strain subsets were then determined and analyzed. Resulting peak strains (0.124–0.328) were found to be within the range for concussion reported in the literature. The results demonstrated that falls and collisions produced larger strain subsets in the cerebrum than puck impacts which is likely a reflection of longer impact duration for falls and collisions than puck impacts. For each impact event, impact site was also found to produce strain subsets of varying size and configuration. The results of this study suggest that the location and number of brain regions which can be damaged depend on the loading conditions of the impact.