Search results for: soft tissue hypertrophy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2429

Search results for: soft tissue hypertrophy

1859 Toward an Informed Capacity Development Program in Inclusive and Sustainable Agricultural and Rural Development

Authors: Maria Ana T. Quimbo

Abstract:

As the Southeast Asian Regional Center for Graduate Study and Research in Agriculture (SEARCA) approaches its 50th founding anniversary. It continues to pursue its mission of strengthening the capacities of Southeast Asian leaders and institutions under its reformulated mission of Inclusive and Sustainable Agricultural and Rural Development (ISARD). Guided by this mission, this study analyzed the desired and priority capacity development needs of institutions heads and key personnel toward addressing the constraints, problems, and issues related to agricultural and rural development toward achieving their institutional goals. Adopting an exploratory, descriptive research design, the study examined the competency needs at the institutional and personnel levels. A total of 35 institution heads from seven countries and 40 key personnel from eight countries served as research participants. The results showed a variety of competencies in the areas of leadership and management, agriculture, climate change, research, monitoring, and evaluation, planning, and extension or community service. While mismatch was found in a number of desired and priority competency areas as perceived by the respondents, there were also interesting concordant answers in both technical and non-technical areas. Interestingly, the competency needs both desired and prioritized were a combination of “hard” or technical skills and “soft” or interpersonal skills. Policy recommendations were forwarded on the need to continue building capacities in core competencies along ISARD; have a balance of 'hard' skills and 'soft' skills through the use of appropriate training strategies and explicit statement in training objectives, strengthen awareness on “soft” skills through its integration in workplace culture, build capacity on action research, continue partnerships encourage mentoring, prioritize competencies, and build capacity of desired and priority competency areas.

Keywords: capacity development, competency needs assessment, sustainability and development, ISARD

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1858 Promoter Methylation of RASSF1A and MGMT Genes in Head and Neck Squamous Cell Carcinoma

Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

Abstract:

Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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1857 Effects of Whole-Body Vibration Training on Fibrinolytic and Coagulative Factors in Healthy Young Man

Authors: Farshad Ghazalian, Seyed Hossein Alavi

Abstract:

Background: Use of whole body vibration (WBV) as an exercise method has rapidly increased over the last decade. The aim of this study was to evaluate effects of five week whole-body vibration training with different amplitudes and progressive frequencies on fibrinolytic and coagulative factors. Methods: Twenty five healthy male students were divided randomly in three groups: high amplitude vibration group (n=10), low amplitude vibration group (n=10), and control group (n=5). The vibration training consisted of 5 week whole-body vibration 3 times a week with amplitudes 4 and 2 mm and progressive frequencies from 25Hz with increments of 5Hz weekly. Concentrations of fibrinogen, plasminogen, tPA, and PAI-1 before and after 5 weeks of training were measured in plasma samples. Statistical analysis was done using one way analysis of variance. In order to compare pre-test with post test we used Wilcoxon signed ranked test .P<0.05 was considered statistically significant. Results: The 5 week high amplitude vibration training caused a significant improvement in tissue plasminogen activator (tPA) (p=0.028), and PAI-1 (p=0.033), fibrinogen showed decrease albeit not significantly (p=0.052). Plasminogen showed decrease not significantly (p=0.508). Low-amplitude vibration training caused a significant improvement in tissue plasminogen activator (tPA) (p=0.006) and and PAI-1 showed decrease not significantly (p=0.907). Fibrinogen showed decrease albeit not significantly (p=0.19). Plasminogen showed decrease not significantly (p=0.095). However, between groups there was no significant effect on tissue plasminogen activator (tPA) (p = 0.50), PAI-1 (p=0.249), Plasminogen (p=0.742), and fibrinogen (p=0.299). Conclusion: Amplitude of vibrations training is a important variable that effect on fibrino lytic factors.

Keywords: vibration, fibrinolysis, blood coagulation, plasminogen

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1856 Fabrication and Assessment of Poly (butylene succinate)/ Poly (ԑ-caprolactone)/Eucomis Autumnalis Cellulose Bio-Composites for Tissue Engineering Applications

Authors: Kumalo F. I., Malimabe M. A., Gumede T. P., Mosoabisane M. F. T.

Abstract:

This study investigates the fabrication and characterization of bio-nanocomposites consisting of poly (butylene succinate) (PBS) and poly (ԑ-caprolactone) (PCL), reinforced with cellulose extracted from Eucomis autumnalis, a medicinal plant. Bio-nanocomposite films were prepared using the solvent casting method, with cellulose content ranging from 1 to 3 wt%. Comprehensive analysis was conducted using FTIR, SEM, TEM, DSC, TGA, and XRD, to assess morphological, thermal, and structural properties. The results indicated significant improvements in the thermal stability and morphological properties with increasing cellulose content, showcasing the potential of these materials for tissue engineering applications. The use of cellulose extracted from a medicinal plant highlight the potential for sustainable and biocompatible materials in biomedical applications.

Keywords: Bionanocomposites, poly(butylene succinate), poly(caprolactone), eucomis autumnalis, medicinal plant

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1855 Piled Critical Size Bone-Biomimetic and Biominerizable Nanocomposites: Formation of Bioreactor-Induced Stem Cell Gradients under Perfusion and Compression

Authors: W. Baumgartner, M. Welti, N. Hild, S. C. Hess, W. J. Stark, G. Meier Bürgisser, P. Giovanoli, J. Buschmann

Abstract:

Perfusion bioreactors are used to solve problems in tissue engineering in terms of sufficient nutrient and oxygen supply. Such problems especially occur in critical size grafts because vascularization is often too slow after implantation ending up in necrotic cores. Biominerizable and biocompatible nanocomposite materials are attractive and suitable scaffold materials for bone tissue engineering because they offer mineral components in organic carriers – mimicking natural bone tissue. In addition, human adipose derived stem cells (ASCs) can potentially be used to increase bone healing as they are capable of differentiating towards osteoblasts or endothelial cells among others. In the present study, electrospun nanocomposite disks of poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/a-CaP) were seeded with human ASCs and eight disks were stacked in a bioreactor running with normal culture medium (no differentiation supplements). Under continuous perfusion and uniaxial cyclic compression, load-displacement curves as a function of time were assessed. Stiffness and energy dissipation were recorded. Moreover, stem cell densities in the layers of the piled scaffold were determined as well as their morphologies and differentiation status (endothelial cell differentiation, chondrogenesis and osteogenesis). While the stiffness of the cell free constructs increased over time caused by the transformation of the a-CaP nanoparticles into flake-like apatite, ASC-seeded constructs showed a constant stiffness. Stem cell density gradients were histologically determined with a linear increase in the flow direction from the bottom to the top of the 3.5 mm high pile (r2 > 0.95). Cell morphology was influenced by the flow rate, with stem cells getting more roundish at higher flow rates. Less than 1 % osteogenesis was found upon osteopontin immunostaining at the end of the experiment (9 days), while no endothelial cell differentiation and no chondrogenesis was triggered under these conditions. All ASCs had mainly remained in their original pluripotent status within this time frame. In summary, we have fabricated a critical size bone graft based on a biominerizable bone-biomimetic nanocomposite with preserved stiffness when seeded with human ASCs. The special feature of this bone graft was that ASC densities inside the piled construct varied with a linear gradient, which is a good starting point for tissue engineering interfaces such as bone-cartilage where the bone tissue is cell rich while the cartilage exhibits low cell densities. As such, this tissue-engineered graft may act as a bone-cartilage interface after the corresponding differentiation of the ASCs.

Keywords: bioreactor, bone, cartilage, nanocomposite, stem cell gradient

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1854 Rapid Soil Classification Using Computer Vision with Electrical Resistivity and Soil Strength

Authors: Eugene Y. J. Aw, J. W. Koh, S. H. Chew, K. E. Chua, P. L. Goh, Grace H. B. Foo, M. L. Leong

Abstract:

This paper presents the evaluation of various soil testing methods such as the four-probe soil electrical resistivity method and cone penetration test (CPT) that can complement a newly developed novel rapid soil classification scheme using computer vision, to improve the accuracy and productivity of on-site classification of excavated soil. In Singapore, excavated soils from the local construction industry are transported to Staging Grounds (SGs) to be reused as fill material for land reclamation. Excavated soils are mainly categorized into two groups (“Good Earth” and “Soft Clay”) based on particle size distribution (PSD) and water content (w) from soil investigation reports and on-site visual survey, such that proper treatment and usage can be exercised. However, this process is time-consuming and labor-intensive. Thus, a rapid classification method is needed at the SGs. Four-probe soil electrical resistivity and CPT were evaluated for their feasibility as suitable additions to the computer vision system to further develop this innovative non-destructive and instantaneous classification method. The computer vision technique comprises soil image acquisition using an industrial-grade camera; image processing and analysis via calculation of Grey Level Co-occurrence Matrix (GLCM) textural parameters; and decision-making using an Artificial Neural Network (ANN). It was found from the previous study that the ANN model coupled with ρ can classify soils into “Good Earth” and “Soft Clay” in less than a minute, with an accuracy of 85% based on selected representative soil images. To further improve the technique, the following three items were targeted to be added onto the computer vision scheme: the apparent electrical resistivity of soil (ρ) measured using a set of four probes arranged in Wenner’s array, the soil strength measured using a modified mini cone penetrometer, and w measured using a set of time-domain reflectometry (TDR) probes. Laboratory proof-of-concept was conducted through a series of seven tests with three types of soils – “Good Earth”, “Soft Clay,” and a mix of the two. Validation was performed against the PSD and w of each soil type obtained from conventional laboratory tests. The results show that ρ, w and CPT measurements can be collectively analyzed to classify soils into “Good Earth” or “Soft Clay” and are feasible as complementing methods to the computer vision system.

Keywords: computer vision technique, cone penetration test, electrical resistivity, rapid and non-destructive, soil classification

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1853 Vulnerability Risk Assessment of Non-Engineered Houses Based on Damage Data of the 2009 Padang Earthquake 2009 in Padang City, Indonesia

Authors: Rusnardi Rahmat Putra, Junji Kiyono, Aiko Furukawa

Abstract:

Several powerful earthquakes have struck Padang during recent years, one of the largest of which was an M 7.6 event that occurred on September 30, 2009 and caused more than 1000 casualties. Following the event, we conducted a 12-site microtremor array investigation to gain a representative determination of the soil condition of subsurface structures in Padang. From the dispersion curve of array observations, the central business district of Padang corresponds to relatively soft soil condition with Vs30 less than 400 m/s. because only one accelerometer existed, we simulated the 2009 Padang earthquake to obtain peak ground acceleration for all sites in Padang city. By considering the damage data of the 2009 Padang earthquake, we produced seismic risk vulnerability estimation of non-engineered houses for rock, medium and soft soil condition. We estimated the loss ratio based on the ground response, seismic hazard of Padang and the existing damaged to non-engineered structure houses due to Padang earthquake in 2009 data for several return periods of earthquake events.

Keywords: profile, Padang earthquake, microtremor array, seismic vulnerability

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1852 Effects of Soil-Structure Interaction on Seismic Performance of Steel Structures Equipped with Viscous Fluid Dampers

Authors: Faramarz Khoshnoudian, Saeed Vosoughiyan

Abstract:

The main goal of this article is to clarify the soil-structure interaction (SSI) effects on the seismic performance of steel moment resisting frame buildings which are rested on soft soil and equipped with viscous fluid dampers (VFDs). For this purpose, detailed structural models of a ten-story SMRF with VFDs excluding and including the SSI are constructed first. In order to simulate the dynamic response of the foundation, in this paper, the simple cone model is applied. Then, the nonlinear time-history analysis of the models is conducted using three kinds of earthquake excitations with different intensities. The analysis results have demonstrated that the SSI effects on the seismic performance of a structure equipped with VFDs and supported by rigid foundation on soft soil need to be considered. Also VFDs designed based on rigid foundation hypothesis fail to achieve the expected seismic objective while SSI goes into effect.

Keywords: nonlinear time-history analysis, soil-structure interaction, steel moment resisting frame building, viscous fluid dampers

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1851 Portable, Noninvasive and Wireless Near Infrared Spectroscopy Device to Monitor Skeletal Muscle Metabolism during Exercise

Authors: Adkham Paiziev, Fikrat Kerimov

Abstract:

Near Infrared Spectroscopy (NIRS) is one of the biophotonic techniques which can be used to monitor oxygenation and hemodynamics in a variety of human tissues, including skeletal muscle. In the present work, we are offering tissue oximetry (OxyPrem) to measure hemodynamic parameters of skeletal muscles in rest and exercise. Purpose: - To elaborate the new wireless, portable, noninvasive, wearable NIRS device to measure skeletal muscle oxygenation during exercise. - To test this device on brachioradialis muscle of wrestler volunteers by using combined method of arterial occlusion (AO) and NIRS (AO+NIRS). Methods: Oxyprem NIRS device has been used together with AO test. AO test and Isometric brachioradialis muscle contraction experiments have been performed on one group of wrestler volunteers. ‘Accu- Measure’ caliper (USA) to measure skinfold thickness (SFT) has been used. Results: Elaborated device consists on power supply box, a sensor head and installed ‘Tubis’ software for data acquisition and to compute deoxyhemoglobin ([HHb), oxyhemoglobin ([O2Hb]), tissue oxygenation (StO2) and muscle tissue oxygen consumption (mVO2). Sensor head consists on four light sources with three light emitting diodes with nominal wavelengths of 760 nm, 805 nm, and 870 nm, and two detectors. AO and isometric voluntary forearm muscle contraction (IVFMC) on five healthy male subjects (23,2±0.84 in age, 0.43±0.05cm of SFT ) and four female subjects (22.0±1.0 in age and 0.24±0.04 cm SFT) has been measured. mVO2 for control group has been calculated (-0.65%/sec±0.07) for male and -0.69%/±0.19 for female subjects). Tissue oxygenation index for wrestlers in average about 75% whereas for control group StO2 =63%. Second experiment was connected with quality monitoring muscle activity during IVFMC at 10%,30% and 50% of MVC. It has been shown, that the concentration changes of HbO2 and HHb positively correlated to the contraction intensity. Conclusion: We have presented a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The miniaturized NIRS sensor and the usage of wireless communication make the whole device have a compact-size, thus can be used in muscle monitoring.

Keywords: skeletal muscle, oxygenation, instrumentation, near infrared spectroscopy

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1850 The Value of Serum Procalcitonin in Patients with Acute Musculoskeletal Infections

Authors: Mustafa Al-Yaseen, Haider Mohammed Mahdi, Haider Ali Al–Zahid, Nazar S. Haddad

Abstract:

Background: Early diagnosis of musculoskeletal infections is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. White blood cell count, erythrocyte sedimentation rate, and C-reactive protein are not specific as they can also be elevated in conditions other than bacterial infections. Materials Culture and sensitivity is not a true gold standard due to its varied positivity rates. Serum Procalcitonin is one of the new laboratory markers for pyogenic infections. The objective of this study is to assess the value of PCT in the diagnosis of soft tissue, bone, and joint infections. Patients and Methods: Patients of all age groups (seventy-four patients) with a diagnosis of musculoskeletal infection are prospectively included in this study. All patients were subjected to White blood cell count, erythrocyte sedimentation rate, C-reactive protein, and serum Procalcitonin measurements. A healthy non infected outpatient group (twenty-two patients) taken as a control group and underwent the same evaluation steps as the study group. Results: The study group showed mean Procalcitonin levels of 1.3 ng/ml. Procalcitonin, at 0.5 ng/ml, was (42.6%) sensitive and (95.5%) specific in diagnosing of musculoskeletal infections with (positive predictive value of 87.5% and negative predictive value of 48.3%) and (positive likelihood ratio of 9.3 and negative likelihood ratio of 0.6). Conclusion: Serum Procalcitonin, at a cut – off of 0.5 ng/ml, is a specific but not sensitive marker in the diagnosis of musculoskeletal infections, and it can be used effectively to rule in the diagnosis of infection but not to rule out it.

Keywords: procalcitonin, infection, labratory markers, musculoskeletal

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1849 An Electron Microscopic Study of Developing Human Fetal Pancreas

Authors: Gupta Renu, T. S. Roy

Abstract:

Introduction: For the prospect of successful replacement therapies in treatment of Diabetes mallitus it is necessary to know events occurring during normal human pancreas development. Literature of human pancreas development are few in number as well as mainly related to first trimester because of ethical and technical difficulties. So the study was conducted on 12 fetuses from 12 gestational weeks (GW) to 5 months of infant to know normal development of exocrine and endocrine part of human pancreas. Material and Methods: Human fetalpancreases were screened by haematoxyline and eosin staining and done electron microscopy for suitable specimens to know ultrastructural detail of fetal pancreas. Results:It was observed arborized tubules, the cells budding out from these tubules differentiated into primitive acini and islets in 12thGW. At 14 weeks scanty granules were observed in the endocrine cells which coincided with the capillary invasion of the islets. The ducts and acini were surrounded by well-organized connective tissue. The acinihad elongated cells, small amount of cytoplasm and large open face euchromatic nuclei with single nucleolus. The mature form of islets of Langerhans was observed close to the acini and duct in 20 GW fetus. Connective tissue around the duct was well organized.No significant developmental change was observed early postnatal, infant. Conclusion: The development of both component exocrine as well as endocrine part of human fetal pancreas was studied by light and electron microscopy. Observations suggested that the fetal pancreas contained mainly ducts, few acini, many centroacinar cells, and large undifferentiated tissue.

Keywords: gestational weeks (GW), acini, islets of Langerhans, ducts

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1848 Model Studies on Shear Behavior of Reinforced Reconstituted Clay

Authors: B. A. Mir, A. Juneja

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In this paper, shear behavior of reconstituted clay reinforced with varying diameter of sand compaction piles with area replacement-ratio (as) of 6.25, 10.24, 16, 20.25 and 64% in 100mm diameter and 200mm long clay specimens is modeled using consolidated drained and undrained triaxial tests under different confining pressures ranging from 50kPa to 575kPa. The test results show that the stress-strain behavior of the clay was highly influenced by the presence of SCP. The insertion of SCPs into soft clay has shown to have a positive effect on the load carrying capacity of the clay, resulting in a composite soil mass that has greater shear strength and improved stiffness compared to the unreinforced clay due to increased reinforcement area ratio. In addition, SCP also acts as vertical drain in the clay thus accelerating the dissipation of excess pore water pressures that are generated during loading by shortening the drainage path and activating radial drainage, thereby reducing post-construction settlement. Thus, sand compaction piles currently stand as one of the most viable and practical techniques for improving the mechanical properties of soft clays.

Keywords: reconstituted clay, SCP, shear strength, stress-strain response, triaxial tests

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1847 Regulation on Macrophage and Insulin Resistance after Aerobic Exercise in High-Fat Diet Mice

Authors: Qiaofeng Guo

Abstract:

Aims: Obesity is often accompanied by insulin resistance (IR) and whole-body inflammation. Aerobic exercise is an effective treatment to improve insulin resistance and inflammation. However, the anti-inflammatory mechanisms of exercise on epididymal and subcutaneous adipose remain to be elucidated. Here, we compared the macrophage polarization between epididymal and subcutaneous adipose after aerobic exercise. Methods: Male C57BL/6 mice were fed a normal diet group or a high-fat diet group for 12 weeks and performed aerobic training on a treadmill at 55%~65% VO₂ max for eight weeks. Food intake, body weight, and fasting blood glucose levels were monitored weekly. The intraperitoneal glucose tolerance test was to evaluate the insulin resistance model. Fat mass, blood lipid profile, serum IL-1β, TNF-α levels, and CD31/CD206 rates were analysed after the intervention. Results: FBG (P<0.01), AUCIPGTT (P<0.01), and HOMA-IR (P<0.01) increased significantly for a high-fat diet and decreased significantly after the exercise. Eight weeks of aerobic exercise attenuated HFD-induced weight gain and glucose intolerance and improved insulin sensitivity. Serum IL-1β, TNF-α, CD11C/CD206 expression in subcutaneous adipose tissue were not changed before and after exercise, but not in epididymal adipose tissue (P<0.01). Conclusion: Insulin resistance is not accompanied by chronic inflammation and M1 polarization of subcutaneous adipose tissue macrophages in high-fat diet mice. Aerobic exercise effectively improved lipid metabolism and insulin sensitivity, which may be closely associated with reduced M1 polarization of epididymal adipose macrophages.

Keywords: aerobic exercise, insulin resistance, chronic inflammation, adipose, macrophage polarization

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1846 Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application

Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee

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Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.

Keywords: nanofiber, tissue, mesh, drug

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1845 Hydrogel Hybridizing Temperature-Cured Dissolvable Gelatin Microspheres as Non-Anchorage Dependent Cell Carriers for Tissue Engineering Applications

Authors: Dong-An Wang

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All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

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1844 A Sub-Conjunctiva Injection of Rosiglitazone for Anti-Fibrosis Treatment after Glaucoma Filtration Surgery

Authors: Yang Zhao, Feng Zhang, Xuanchu Duan

Abstract:

Trans-differentiation of human Tenon fibroblasts (HTFs) to myo-fibroblasts and fibrosis of episcleral tissue are the most common reasons for the failure of glaucoma filtration surgery, with limited treatment options like antimetabolites which always have side-effects such as leakage of filter bulb, infection, hypotony, and endophthalmitis. Rosiglitazone, a specific thiazolidinedione is a synthetic high-affinity ligand for PPAR-r, which has been used in the treatment of type2 diabetes, and found to have pleiotropic functions against inflammatory response, cell proliferation and tissue fibrosis and to benefit to a variety of diseases in animal myocardium models, steatohepatitis models, etc. Here, in vitro we cultured primary HTFs and stimulated with TGF- β to induced myofibrogenic, then treated cells with Rosiglitazone to assess for fibrogenic response. In vivo, we used rabbit glaucoma model to establish the formation of post- trabeculectomy scarring. Then we administered subconjunctival injection with Rosiglitazone beside the filtering bleb, later protein, mRNA and immunofluorescence of fibrogenic markers are checked, and filtering bleb condition was measured. In vitro, we found Rosiglitazone could suppressed proliferation and migration of fibroblasts through macroautophagy via TGF- β /Smad signaling pathway. In vivo, on postoperative day 28, the mean number of fibroblasts in Rosiglitazone injection group was significantly the lowest and had the least collagen content and connective tissue growth factor. Rosiglitazone effectively controlled human and rabbit fibroblasts in vivo and in vitro. Its subconjunctiiva application may represent an effective, new avenue for the prevention of scarring after glaucoma surgery.

Keywords: fibrosis, glaucoma, macroautophagy, rosiglitazone

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1843 Assessment of Breeding Soundness by Comparative Radiography and Ultrasonography of Rabbit Testes

Authors: Adenike O. Olatunji-Akioye, Emmanual B Farayola

Abstract:

In order to improve the animal protein recommended daily intake of Nigerians, there is an upsurge in breeding of hitherto shunned food animals one of which is the rabbit. Radiography and ultrasonography are tools for diagnosing disease and evaluating the anatomical architecture of parts of the body non-invasively. As the rabbit is becoming a more important food animal, to achieve improved breeding of these animals, the best of the species form a breeding stock and will usually depend on breeding soundness which may be evaluated by assessment of the male reproductive organs by these tools. Four male intact rabbits weighing between 1.2 to 1.5 kg were acquired and acclimatized for 2 weeks. Dorsoventral views of the testes were acquired using a digital radiographic machine and a 5 MHz portable ultrasound scanner was used to acquire images of the testes in longitudinal, sagittal and transverse planes. Radiographic images acquired revealed soft tissue images of the testes in all rabbits. The testes lie in individual scrotal sacs sides on both sides of the midline at the level of the caudal vertebrae and thus are superimposed by caudal vertebrae and the caudal limits of the pelvic girdle. The ultrasonographic images revealed mostly homogenously hypoechogenic testes and a hyperechogenic mediastinum testis. The dorsal and ventral poles of the testes were heterogeneously hypoechogenic and correspond to the epididymis and spermatic cord. The rabbit is unique in the ability to retract the testes particularly when stressed and so careful and stressless handling during the procedures is of paramount importance. The imaging of rabbit testes can be safely done using both imaging methods but ultrasonography is a better method of assessment and evaluation of soundness for breeding.

Keywords: breeding soundness, rabbit, radiography, ultrasonography

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1842 Measurement of Fatty Acid Changes in Post-Mortem Belowground Carcass (Sus-scrofa) Decomposition: A Semi-Quantitative Methodology for Determining the Post-Mortem Interval

Authors: Nada R. Abuknesha, John P. Morgan, Andrew J. Searle

Abstract:

Information regarding post-mortem interval (PMI) in criminal investigations is vital to establish a time frame when reconstructing events. PMI is defined as the time period that has elapsed between the occurrence of death and the discovery of the corpse. Adipocere, commonly referred to as ‘grave-wax’, is formed when post-mortem adipose tissue is converted into a solid material that is heavily comprised of fatty acids. Adipocere is of interest to forensic anthropologists, as its formation is able to slow down the decomposition process. Therefore, analysing the changes in the patterns of fatty acids during the early decomposition process may be able to estimate the period of burial, and hence the PMI. The current study concerned the investigation of the fatty acid composition and patterns in buried pig fat tissue. This was in an attempt to determine whether particular patterns of fatty acid composition can be shown to be associated with the duration of the burial, and hence may be used to estimate PMI. The use of adipose tissue from the abdominal region of domestic pigs (Sus-scrofa), was used to model the human decomposition process. 17 x 20cm piece of pork belly was buried in a shallow artificial grave, and weekly samples (n=3) from the buried pig fat tissue were collected over an 11-week period. Marker fatty acids: palmitic (C16:0), oleic (C18:1n-9) and linoleic (C18:2n-6) acid were extracted from the buried pig fat tissue and analysed as fatty acid methyl esters using the gas chromatography system. Levels of the marker fatty acids were quantified from their respective standards. The concentrations of C16:0 (69.2 mg/mL) and C18:1n-9 (44.3 mg/mL) from time zero exhibited significant fluctuations during the burial period. Levels rose (116 and 60.2 mg/mL, respectively) and fell starting from the second week to reach 19.3 and 18.3 mg/mL, respectively at week 6. Levels showed another increase at week 9 (66.3 and 44.1 mg/mL, respectively) followed by gradual decrease at week 10 (20.4 and 18.5 mg/mL, respectively). A sharp increase was observed in the final week (131.2 and 61.1 mg/mL, respectively). Conversely, the levels of C18:2n-6 remained more or less constant throughout the study. In addition to fluctuations in the concentrations, several new fatty acids appeared in the latter weeks. Other fatty acids which were detectable in the time zero sample, were lost in the latter weeks. There are several probable opportunities to utilise fatty acid analysis as a basic technique for approximating PMI: the quantification of marker fatty acids and the detection of selected fatty acids that either disappear or appear during the burial period. This pilot study indicates that this may be a potential semi-quantitative methodology for determining the PMI. Ideally, the analysis of particular fatty acid patterns in the early stages of decomposition could be an additional tool to the already available techniques or methods in improving the overall processes in estimating PMI of a corpse.

Keywords: adipocere, fatty acids, gas chromatography, post-mortem interval

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1841 A Comparative Study of Twin Delayed Deep Deterministic Policy Gradient and Soft Actor-Critic Algorithms for Robot Exploration and Navigation in Unseen Environments

Authors: Romisaa Ali

Abstract:

This paper presents a comparison between twin-delayed Deep Deterministic Policy Gradient (TD3) and Soft Actor-Critic (SAC) reinforcement learning algorithms in the context of training robust navigation policies for Jackal robots. By leveraging an open-source framework and custom motion control environments, the study evaluates the performance, robustness, and transferability of the trained policies across a range of scenarios. The primary focus of the experiments is to assess the training process, the adaptability of the algorithms, and the robot’s ability to navigate in previously unseen environments. Moreover, the paper examines the influence of varying environmental complexities on the learning process and the generalization capabilities of the resulting policies. The results of this study aim to inform and guide the development of more efficient and practical reinforcement learning-based navigation policies for Jackal robots in real-world scenarios.

Keywords: Jackal robot environments, reinforcement learning, TD3, SAC, robust navigation, transferability, custom environment

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1840 Modeling of Radiofrequency Nerve Lesioning in Inhomogeneous Media

Authors: Nour Ismail, Sahar El Kardawy, Bassant Badwy

Abstract:

Radiofrequency (RF) lesioning of nerves have been commonly used to alleviate chronic pain, where RF current preventing transmission of pain signals through the nerve by heating the nerve causing the pain. There are some factors that affect the temperature distribution and the nerve lesion size, one of these factors is the inhomogeneities in the tissue medium. Our objective is to calculate the temperature distribution and the nerve lesion size in a nonhomogenous medium surrounding the RF electrode. A two 3-D finite element models are used to compare the temperature distribution in the homogeneous and nonhomogeneous medium. Also the effect of temperature-dependent electric conductivity on maximum temperature and lesion size is observed. Results show that the presence of a nonhomogeneous medium around the RF electrode has a valuable effect on the temperature distribution and lesion size. The dependency of electric conductivity on tissue temperature increased lesion size.

Keywords: finite element model, nerve lesioning, pain relief, radiofrequency lesion

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1839 A Combination of Mesenchymal Stem Cells and Low-Intensity Ultrasound for Knee Meniscus Regeneration: A Preliminary Study

Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

Abstract:

Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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1838 Spectroscopy Investigation of Ni0.5Zn0.5Fe2O4 Nano Ferrite Prepared by Soft Mechanochemical Synthesis

Authors: Z. Ž. Lazarević, Č. Jovalekić, V. N. Ivanovski, N. Ž. Romčević

Abstract:

Nickel-zinc ferrite, Ni0.5Zn0.5Fe2O4 was prepared by mechanochemical route in a planetary ball mill starting from mixture of the appropriate quantities of the Ni(OH)2, Zn(OH)2 and Fe(OH)3 hydroxide powders. In order to monitor the progress of chemical reaction and confirm phase formation, powder samples obtained after 5 h and 10 h of milling were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), IR, Raman and Mössbauer spectroscopy. It is shown that the soft mechanochemical method, i.e. mechanochemical activation of hydroxides, produces high quality single phase Ni0.5Zn0.5Fe2O4 samples in much more efficient way. From the IR spectroscopy of single phase samples it is obvious that energy of modes depends on the ratio of cations. It is obvious that all samples have more than 5 Raman active modes predicted by group theory in the normal spinel structure. Deconvolution of measured spectra allows one to conclude that all complex bands in the spectra are made of individual peaks with the intensities that vary from spectrum to spectrum. The deconvolution of Raman spectra alows to separate contributions of different cations to a particular type of vibration and to estimate the degree of inversion.

Keywords: ferrite, X-ray diffraction, infrared spectroscopy, Raman spectroscopy, Mössbauer spectroscopy

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1837 Ulnar Parametacarpal Flap for Coverage of Fifth Finger Defects: Propeller Flap Concept

Authors: Ahmed M. Gad, Ahmed S. Hweidi

Abstract:

Background: Defects of the little finger and adjacent areas are not uncommon. It could be a traumatic, post-burn, or after contracture release. Different options could be used for resurfacing these defect, including skin grafts, local or regional flaps. Ulnar para-metacarpal flap described by Bakhach in 1995 based on the distal division of the dorsal branch of the ulnar artery considered a good option for that. In this work, we applied the concept of propeller flap for better mobilization and in-setting of the ulnar para-metacarpal flap. Methods: The study included 15 cases with 4 females and 11 male patients. 10 of the patients had severe post-burn contractures of little finger, and 5 had post-traumatic little finger defects. Contractures were released and resulting soft tissue defects were reconstructed with propeller ulnar para-metacarpal artery flap. The flap based on two main perforators communicating with the palmar system, it was raised based on one of them depending on the extent of the defect and rotated 180 degrees after judicious dissection of the perforator. Results: 13 flaps survived completely, one of the cases developed partial skin loss, which healed by dressing, another flap was completely lost and covered later by a full-thickness skin graft. Conclusion: Ulnar para-metacarpal flap is a reliable option to resurface the little finger as well as adjacent areas. The application of the propeller flap concept based on whether the proximal or distal communicating branch makes the rotation and in-setting of the flap easier.

Keywords: little finger defects, propeller flap, regional hand defects, ulnar parametacarpal flap

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1836 Cytology Is a Promising Tool for the Diagnosis of High-Grade Serous Ovarian Carcinoma from Ascites

Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

Abstract:

Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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1835 A Review of Kinematics and Joint Load Forces in Total Knee Replacements Influencing Surgical Outcomes

Authors: Samira K. Al-Nasser, Siamak Noroozi, Roya Haratian, Adrian Harvey

Abstract:

A total knee replacement (TKR) is a surgical procedure necessary when there is severe pain and/or loss of function in the knee. Surgeons balance the load in the knee and the surrounding soft tissue by feeling the tension at different ranges of motion. This method can be unreliable and lead to early failure of the joint. The ideal kinematics and load distribution have been debated significantly based on previous biomechanical studies surrounding both TKRs and normal knees. Intraoperative sensors like VERASENSE and eLibra have provided a method for the quantification of the load indicating a balanced knee. A review of the literature written about intraoperative sensors and tension/stability of the knee was done. Studies currently debate the quantification of the load in medial and lateral compartments specifically. However, most research reported that following a TKR the medial compartment was loaded more heavily than the lateral compartment. In several cases, these results were shown to increase the success of the surgery because they mimic the normal kinematics of the knee. In conclusion, most research agrees that an intercompartmental load differential of between 10 and 20 pounds, where the medial load was higher than the lateral, and an absolute load of less than 70 pounds was ideal. However, further intraoperative sensor development could help improve the accuracy and understanding of the load distribution on the surgical outcomes in a TKR. A reduction in early revision surgeries for TKRs would provide an improved quality of life for patients and reduce the economic burden placed on both the National Health Service (NHS) and the patient.

Keywords: intraoperative sensors, joint load forces, kinematics, load balancing, and total knee replacement

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1834 Geotechnical Investigation of Soil Foundation for Ramps of Dawar El-Tawheed Bridge in Jizan City, Kingdom of Saudi Arabia

Authors: Ali H. Mahfouz, Hossam E. M. Sallam, Abdulwali Wazir, Hamod H. Kharezi

Abstract:

The soil profile at site of the bridge project includes soft fine grained soil layer located between 5.0 m to 11.0 m in depth, it has high water content, low SPT no., and low bearing capacity. The clay layer induces high settlement due to surcharge application of earth embankment at ramp T1, ramp T2, and ramp T3 especially at heights from 9m right 3m. Calculated settlement for embankment heights less than 3m may be accepted regarding Saudi Code for soil and foundation. The soil and groundwater at the project site comprise high contents of sulfates and chlorides of high aggressively on concrete and steel bars, respectively. Regarding results of the study, it has been recommended to use stone column piles or new technology named PCC piles as soil improvement to improve the bearing capacity of the weak layer. The new technology is cast in-situ thin wall concrete pipe piles (PCC piles), it has economically advantageous and high workability. The technology can save time of implementation and cost of application is almost 30% of other types of piles.

Keywords: soft foundation soil, bearing capacity, bridge ramps, soil improvement, geogrid, PCC piles

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1833 Development of Strategic Cooperation in Managing Thailand-Myanmar Borders: Roles of Education in Enhancing Sustainability

Authors: Rungrot Trongsakul

Abstract:

This paper was aimed to study the strategic cooperation development of Thailand in accordance with the door open policy of Myanmar, by use of DIMES Model: Diplomacy, Information, Military and Economics, Socio-Culture. This research employed qualitative method, aiming to study, analyze and synthesize the content of laws, policies, relevant research papers and documents, and relevant theories, and to study external environment and national power based on DIMES Model. The five steps of strategic development utilized in this study included (1) conceptual framework and definition; (2) environmental scanning; (3) assessing; (4) determining; and (5) drafting strategic plan. The suggested strategies were based on the concept of 'Soft Power'. Therefore, the determination of measures, action plans or projects as strategic means of public and private organizations should be based on sincere participation among people and communities living on the borders shared by both countries. Adoption of education, learning and sharing process is a key to building sustainability of the countries’ strategic cooperation, while an application of 'Soft Power' in all dimensions of the cooperation between the two countries was suggested.

Keywords: education, strategic cooperation, Thailand-Myanmar borders, sustainability

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1832 Characterization of Retinal Pigmented Cell Epithelium Cell Sheet Cultivated on Synthetic Scaffold

Authors: Tan Yong Sheng Edgar, Yeong Wai Yee

Abstract:

Age-related macular degeneration (AMD) is one of the leading cause of blindness. It can cause severe visual loss due to damaged retinal pigment epithelium (RPE). RPE is an important component of the retinal tissue. It functions as a transducing boundary for visual perception making it an essential factor for sight. The RPE also functions as a metabolically complex and functional cell layer that is responsible for the local homeostasis and maintenance of the extra photoreceptor environment. Thus one of the suggested method of treating such diseases would be regenerating these RPE cells. As such, we intend to grow these cells using a synthetic scaffold to provide a stable environment that reduces the batch effects found in natural scaffolds. Stiffness of the scaffold will also be investigated to determine the optimal Young’s modulus for cultivating these cells. The cells will be generated into a monolayer cell sheet and their functions such as formation of tight junctions and gene expression patterns will be assessed to evaluate the cell sheet quality compared to a native RPE tissue.

Keywords: RPE, scaffold, characterization, biomaterials, colloids and nanomedicine

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1831 Stress-Strain Relation for Human Trabecular Bone Based on Nanoindentation Measurements

Authors: Marek Pawlikowski, Krzysztof Jankowski, Konstanty Skalski, Anna Makuch

Abstract:

Nanoindentation or depth-sensing indentation (DSI) technique has proven to be very useful to measure mechanical properties of various tissues at a micro-scale. Bone tissue, both trabecular and cortical one, is one of the most commonly tested tissues by means of DSI. Most often such tests on bone samples are carried out to compare the mechanical properties of lamellar and interlamellar bone, osteonal bone as well as compact and cancellous bone. In the paper, a relation between stress and strain for human trabecular bone is presented. The relation is based on the results of nanoindentation tests. The formulation of a constitutive model for human trabecular bone is based on nanoindentation tests. In the study, the approach proposed by Olivier-Pharr is adapted. The tests were carried out on samples of trabecular tissue extracted from human femoral heads. The heads were harvested during surgeries of artificial hip joint implantation. Before samples preparation, the heads were kept in 95% alcohol in temperature 4 Celsius degrees. The cubic samples cut out of the heads were stored in the same conditions. The dimensions of the specimens were 25 mm x 25 mm x 20 mm. The number of 20 samples have been tested. The age range of donors was between 56 and 83 years old. The tests were conducted with the indenter spherical tip of the diameter 0.200 mm. The maximum load was P = 500 mN and the loading rate 500 mN/min. The data obtained from the DSI tests allows one only to determine bone behoviour in terms of nanoindentation force vs. nanoindentation depth. However, it is more interesting and useful to know the characteristics of trabecular bone in the stress-strain domain. This allows one to simulate trabecular bone behaviour in a more realistic way. The stress-strain curves obtained in the study show relation between the age and the mechanical behaviour of trabecular bone. It was also observed that the bone matrix of trabecular tissue indicates an ability of energy absorption.

Keywords: constitutive model, mechanical behaviour, nanoindentation, trabecular bone

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1830 A Secreted Protein Can Attenuate High Fat Diet Induced Obesity and Metabolic Syndrome in Mice

Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

Abstract:

Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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