Search results for: bone morphogenetic signaling
Commenced in January 2007
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Edition: International
Paper Count: 1133

Search results for: bone morphogenetic signaling

803 Osteitis in the Diabetic Foot and the Risk Factor on the Population

Authors: Mohamed Amine Adaour, Mohamed Sadek Bachene, Mosaab Fortassi, Wafaa Siouda

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Foot infections are responsible for a significant number of hospitalizations and amputations in diabetic patients. The objective of our study is to analyze and evaluate the management of diabetic foot in a surgical setting. A retrospective study was conducted based on a selected case of suspected diabetic foot infections of osteitis treated at the Mohamed Boudiaf hospital in Medea.The case was reiterated as a therapeutic charge, consisting of treating first the infection of the soft tissues, then the osteitis: biopsy after at least 15 days of cessation of antibiotic therapy. Successful treatment of osteitis was defined at the end of a follow-up period of complete wound healing, lack of bone resection/amputation surgery at the initial bone site during follow-up , Instead, biopsies are prescribed in the treatment of soft tissue infection. The mean duration of treatment for soft tissue infection was 2-3 weeks, the duration of the antibiotic-free window of therapy prior to bone biopsy was 2-4 weeks. This patient received medical management without surgical resection. The success rate for treating osteitis at one year was 73%, and healing at one year was 88%.It is often limited to a sausage of the foot at the cost of repeated amputations. The best management remains prevention, which necessarily involves setting up a specialized and adapted centre.

Keywords: osteitis, antibiotic, biopsy, diabetic foot

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802 Open Joint Surgery for Temporomandibular Joint Internal Derangement: Wilkes Stages III-V

Authors: T. N. Goh, M. Hashmi, O. Hussain

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Temporomandibular joint (TMJ) dysfunction (TMD) is a condition that may affect patients via restricted mouth opening, significant pain during normal functioning, and/or reproducible joint noise. TMD includes myofascial pain, TMJ functional derangements (internal derangement, dislocation), and TMJ degenerative/inflammatory joint disease. Internal derangement (ID) is the most common cause of TMD-related clicking and locking. These patients are managed in a stepwise approach, from patient education (homecare advice and analgesia), splint therapy, physiotherapy, botulinum toxin treatment, to arthrocentesis. Arthrotomy is offered when the aforementioned treatment options fail to alleviate symptoms and improve quality of life. The aim of this prospective study was to review the outcomes of jaw joint open surgery in TMD patients. Patients who presented from 2015-2022 at the Oral and Maxillofacial Surgery Department in the Doncaster NHS Foundation Trust, UK, with a Wilkes classification of III -V were included. These patients underwent either i) discopexy with bone-anchoring suture (9); ii) intrapositional temporalis flap (ITF) with bone-anchoring suture (3); iii) eminoplasty and discopexy with suturing to the capsule (3); iii) discectomy + ITF with bone-anchoring suture (1); iv) discoplasty + bone-anchoring suture (1); v) ITF (1). Maximum incisal opening (MIO) was assessed pre-operatively and at each follow-up. Pain score, determined via the visual analogue scale (VAS, with 0 being no pain and 10 being the worst pain), was also recorded. A total of 18 eligible patients were identified with a mean age of 45 (range 22 - 79), of which 16 were female. The patients were scored by Wilkes Classification as III (14), IV (1), or V (4). Twelve patients had anterior disc displacement without reduction (66%) and six had degenerative/arthritic changes (33%) to the TMJ. The open joint procedure resulted in an increase in MIO and reduction in pain VAS and for the majority of patients, across all Wilkes Classifications. Pre-procedural MIO was 22.9 ± 7.4 mm and VAS was 7.8 ± 1.5. At three months post-procedure there was an increase in MIO to 34.4 ± 10.4 mm (p < 0.01) and a decrease in the VAS to 1.5 ± 2.9 (p < 0.01). Three patients were lost to follow-up prior to six months. Six were discharged at six month review and five patients were discharged at 12 months review as they were asymptomatic with good mouth opening. Four patients are still attending for annual botulinum toxin treatment. Two patients (Wilkes III and V) subsequently underwent TMJ replacement (11%). One of these patients (Wilkes III) had improvement initially to MIO of 40 mm, but subsequently relapsed to less than 20 mm due to lack of compliance with jaw rehabilitation device post-operatively. Clinical improvements in 89% of patients within the study group were found, with a return to near normal MIO range and reduced pain score. Intraoperatively, the operator found bone-anchoring suture used for discopexy/discoplasty more secure than the soft tissue anchoring suturing technique.

Keywords: bone anchoring suture, open temporomandibular joint surgery, temporomandibular joint, temporomandibular joint dysfunction

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801 Characteristic of Taro (Colocasia esculenta), Seaweed (Gracilaria Sp.), and Fishes Bone Collagens Flour Based Analog Rice

Authors: Y. S. Darmanto, P. H. Riyadi, S. Susanti

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Recently, approximately 9.1 million people of 237.56 million of Indonesian population suffer diabetes. Such condition was caused by high rice consumption of most Indonesian people. It has been known that rice contains low amylose, high calorie, and possesses hyperglycemic properties. Through this study, we tried to solve that problem by creating a super food in order to provide an alternative healthy and balanced diet. We formulated Taro and Seaweed flour based analog rice that fortified by various fishes bone collagens. Corms of Taro contain easily digestible starch and seaweed is rich in fiber, vitamin, and mineral. That mixture was fortified with collagen-containing unique amino acids such as glysine, lysine, alanine, arginine, proline, and hydroxyprolin. Subsequently, super analog rice was characterized about its nutritional composition such are proximate analyses, water, dietary fiber and amylose content. Furthermore, its morphological structure was analyzed by using scanning electron microscopy while the level of consumer preferences was performed by hedonic test. Results demonstrated that fortification by using various fishes bone collagen into analog rice were significantly different in nutritional composition, morphological structure as well as its preferences. Thus, this study was expected as new avenue in functional food discovery especially in the treatment and prevention of diabetic diseases.

Keywords: analogue rice, taro, seaweed, collagen

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800 Genetically Informed Precision Drug Repurposing for Rheumatoid Arthritis

Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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799 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine

Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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798 Enacting Educational Technology Affordances as Mechanisms Responsible for Gaining Epistemological Access: A Case of Underprivileged Students at Higher Institutions in Northern Nigeria

Authors: Bukhari Badamasi, Chidi G. Ononiwu

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Globally, educational technology (EdTech) has become a known catalyst for gaining access to education, job creation, and national development of a nation. Howbeit, it is common understanding that higher institutions continue to deploy digital technologies, to help provide access to education, but in most case, it is somehow institutional access not epistemological access especially in sub Saharan African higher institutions. Some scholars, however, lament the fact that studies on educational technology affordances are mostly fragmented because they focus on specific theme or sub aspect of access (i.e., institutional access). Thus, drawing from the Archer Morphogenetic approach, and Gibson Affordance theory, and applying critical realist based Danermark model for explanatory research, the study seeks to conduct a realist case study on underprivileged students in Higher institutions on how they gain epistemological access by enacting educational technology (EdTech) affordances.

Keywords: affordance, epistemological access, educational technology, underprivileged students

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797 Cells Detection and Recognition in Bone Marrow Examination with Deep Learning Method

Authors: Shiyin He, Zheng Huang

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In this paper, deep learning methods are applied in bio-medical field to detect and count different types of cells in an automatic way instead of manual work in medical practice, specifically in bone marrow examination. The process is mainly composed of two steps, detection and recognition. Mask-Region-Convolutional Neural Networks (Mask-RCNN) was used for detection and image segmentation to extract cells and then Convolutional Neural Networks (CNN), as well as Deep Residual Network (ResNet) was used to classify. Result of cell detection network shows high efficiency to meet application requirements. For the cell recognition network, two networks are compared and the final system is fully applicable.

Keywords: cell detection, cell recognition, deep learning, Mask-RCNN, ResNet

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796 Effect of Class V Cavity Configuration and Loading Situation on the Stress Concentration

Authors: Jia-Yu Wu, Chih-Han Chang, Shu-Fen Chuang, Rong-Yang Lai

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Objective: This study was to examine the stress distribution of tooth with different class V restorations under different loading situations and geometry by 3D finite element (FE) analysis. `Methods: A series of FE models of mandibular premolars containing class V cavities were constructed using micro-CT. The class V cavities were assigned as the combinations of different cavity depths x occlusal -gingival heights: 1x2, 1x4, 2x2, and 2x4 mm. Three alveolar bone loss conditions were examined: 0, 1, and 2 mm. 200 N force was exerted on the buccal cusp tip under various directions (vertical, V; obliquely 30° angled, O; oblique and parallel the individual occlusal cavity wall, P). A 3-D FE analysis was performed and the von-Mises stress was used to summarize the data of stress distribution and maximum stress. Results: The maximal stress did not vary in different alveolar bone heights. For each geometry, the maximal stress was found at bilateral corners of the cavity. The peak stress of restorations was significantly higher under load P compared to those under loads V and O while the latter two were similar. 2x2mm cavity exhibited significantly increased (2.88 fold) stress under load P compared to that under load V, followed by 1x2mm (2.11 fold), 2x4mm (1.98 fold) and 1x4mm (1.1fold). Conclusion: Load direction causes the greatest impact on the results of stress, while the effect of alveolar bone loss is minor. Load direction parallel to the cavity wall may enhance the stress concentration especially in deep and narrow class cavities.

Keywords: class v restoration, finite element analysis, loading situation, stress

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795 Apatite-Forming Ability of Doped-Ceria Coatings for Orthopedic Implants

Authors: Ayda Khosravanihaghighi, Pramod Koshy, Bill Walsh, Vedran Lovric, Charles Christopher Sorrell

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There is an increasing demand for orthopedic implants owing to the increasing numbers of the aging population. Titanium alloy (Ti6Al4V) is a common material used for orthopedic implants owing to its advantageous properties in terms of good corrosion resistance, minimal elastic modulus mismatch with bone, bio-inertness, and high mechanical strength. However, it is important to improve the bioactivity and osseointegration of the titanium alloy and this can be achieved by coating the implant surface with suitable ceramic materials. In the present work, pure and doped-ceria (CeO₂) coatings were deposited by spin coating on the titanium alloy surface in order to enhance the biological interactions between the surface of the implant and the surrounding tissue. In order to examine the bone-binding ability of an implant, simulated body fluid (SBF) tests were conducted in order to assess the capability of apatite layer formation on the surface and thus predict in vivo bone bioactivity. Characterization was done using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses to determine the extent of apatite formation. Preliminary tests showed that the CeO₂ coatings were biocompatible and that the extent of apatite formation and its characteristics can be enhanced by doping with suitable metal ions.

Keywords: apatite layer, biocompatibility, ceria, orthopaedic implant, SBF, spin coater, Ti-implant

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794 Fatigue Test and Stress-Life Analysis of Nanocomposite-Based Bone Fixation Device

Authors: Jisoo Kim, Min Su Lee, Sunmook Lee

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Durability assessment of nanocomposite-based bone fixation device was performed by flexural fatigue tests, for which the changes in the life cycles of nanocomposite samples synthesized by blending bioabsorbable polymer (PLGA) and ceramic nanoparticles (β-TCP) with different ratios were monitored. The nanocomposite samples were kept in a constant temperature/humidity chamber at 37°C/50%RH for varied incubation periods for the degradation of nanocomposite samples under the temperature/humidity stress. It was found that the life cycles were increasing as the incubation time in the chamber were increasing in the initial stage irrespective of sample compositions, which was due to the annealing effect of the polymer. However, the life cycle was getting shorter as the incubation time increased afterward, which was due to the overall degradation of nanocomposites. It was found that the life cycle of the nanocomposite sample with high ceramic content was shorter than the one with low ceramic content, which was attributed to the increased brittleness of the composite with high ceramic content. The changes in chemical properties were also monitored by FT-IR, which indicated that the degradation of the biodegradable polymer could be confirmed by the increased intensities of carboxyl groups and hydroxyl groups since the hydrolysis of ester bonds connecting two successive monomers yielded carboxyl end groups and hydroxyl groups.

Keywords: bioabsorbable polymer, bone fixation device, ceramic nanoparticles, durability assessment, fatigue test

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793 Characterization of Femur Development in Mice: A Computational Approach

Authors: Moncayo Donoso Miguelangel, Guevara Morales Johana, Kalenia Flores Kalenia, Barrera Avellaneda Luis Alejandro, Garzon Alvarado Diego Alexander

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In mammals, long bones are formed by ossification of a cartilage mold during early embryonic development, forming structures called secondary ossification centers (SOCs), a primary ossification center (POC) and growth plates. This last structure is responsible for long bone growth. During the femur growth, the morphology of the growth plate and the SOCs may vary during different developmental stages. So far there are no detailed morphological studies of the development process from embryonic to adult stages. In this work, we carried out a morphological characterization of femur development from embryonic period to adulthood in mice. 15, 17 and 19 days old embryos and 1, 7, 14, 35, 46 and 52 days old mice were used. Samples were analyzed by a computational approach, using 3D images obtained by micro-CT imaging. Results obtained in this study showed that femur, its growth plates and SOCs undergo morphological changes during different stages of development, including changes in shape, position and thickness. These variations may be related with a response to mechanical loads imposed for muscle development surrounding the femur and a high activity during early stages necessary to support the high growth rates during first weeks and years of development. This study is important to improve our knowledge about the ossification patterns on every stage of bone development and characterize the morphological changes of important structures in bone growth like SOCs and growth plates.

Keywords: development, femur, growth plate, mice

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792 Long-Term Effect of Dialysis Therapy for Osteoporosis and Extra-Osseous Calcification in Chronic Renal Failure

Authors: Itsuo Yokoyama, Rikako Kikuti, Naoko Watabe, Tosinori Asai, Sarai Tsuyoshi

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Introduction: Chronic kidney disease presents significant changes in mineral and bone metabolism, referred to as CKD-MBD. These changes lead to decreased bone mass, heightened bone fragility, fractures, and increased vascular and valvular calcification, ultimately impacting cardiovascular outcomes. Key contributors to these complications in dialysis patients include calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the vitamin D hormonal system. Methods: In our outpatient dialysis clinic, we monitor the long-term effects of vascular calcifications by calculating the volume of calcified areas in the abdominal aorta based on CT scan data. The results revealed a progressive nature of vascular calcification. To extend our study, we measured the volume of calcification in bones (vertebrae and femur) corresponding to Hounsfield units of 200 and 300. The study aims to investigate changes in osteoporosis during a 5-year follow-up period and its relationship with extraosseous calcification. Results and Considerations: While extraosseous calcification demonstrated a generally progressive nature, often resistant to medical treatment, the degree of osteoporotic change varied among patients. The majority exhibited continuous osteoporotic changes, while some showed improvement or minimal changes in bone calcification. Variations in the distribution and magnitude of osteoporotic changes were observed between groups based on the timing of hemodialysis initiation during the study. The former group tended to display more osteoporotic changes, possibly attributed to differences in medication between the groups. Other contributing factors may include the patient's age, duration of dialysis, or causes of renal disease. In conclusion, we emphasize the importance of carefully monitoring calcium and phosphate levels and maintaining adequate dialysis therapy to prevent osteoporosis in dialysis patients.

Keywords: CKD-MBD, dialysis, calcification, kidney

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791 Prevalence of Risk Factors of the Female Athlete Triad Among Young Elite Athletes of the World

Authors: Muhammad Saleem

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Background: Inattentive food choices and engagement in excessive physical activities by male athletes can potentially lead to adverse health consequences. Objective: The aim was to ascertain the occurrence of risk factors associated with the Male Athlete Triad among young elite athletes in Pakistan. Methodology: In 2018, a cross-sectional study based on questionnaires was conducted at the Pakistan Sports Board. The study aimed to explore the risk factors related to the Male Athlete Triad in young elite athletes who were part of national training camps in major metropolitan areas. The study included proficient male elite athletes aged 18 to 25 years, capable of understanding the English questionnaire. The athletes completed a survey encompassing aspects like demographic information, educational background, Body Mass Index (BMI), sports involvement, and hours of participation. Additionally, they filled out the Eating Attitude Test-26 (EAT-26) and questionnaires assessing risks of amenorrhea and low bone mineral density. The prevalence of risk factors for each of the three components was individually evaluated. The collected data underwent analysis using SPSS-20, with descriptive statistics being applied. Results: The study comprised a sample of 90 elite athletes (mean age: 23.57 ± 2.37 years, mean BMI: 21.97 ± 1.90) engaged in various sports. The EAT-26 results indicated that 50% of athletes were at risk of developing an eating disorder. Moreover, 83.3% exhibited disordered eating behaviors that necessitated referral. Risks for amenorrhea were observed in 15% of the participants, and regarding low bone mineral density, notable risks were absent except for the consumption of caffeinated beverages, which was noted in 51.7% of participants. Conclusion: The study identified a significant prevalence of disordered eating risk among male elite athletes in Pakistan. However, the risks associated with amenorrhea and low bone mineral density were not a major concern in this particular group.

Keywords: Pakistan, osteoporosis, female athlete triad, bone mineral density, athlete, amenorrhea, eating disorders

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790 Numerical Analysis of Mandible Fracture Stabilization System

Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski

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The aim of the presented work is to recognize the impact of mini-plate application approach on the stress and displacement within the stabilization devices and surrounding bones. The mini-plate osteosynthesis technique is widely used by craniofacial surgeons as an improved replacement of wire connection approach. Many different types of metal plates and screws are used to the physical connection of fractured bones. Below investigation is based on a clinical observation of patient hospitalized with mini-plate stabilization system. Analysis was conducted on a solid mandible geometry, which was modeled basis on the computed tomography scan of the hospitalized patient. In order to achieve most realistic connected system behavior, the cortical and cancellous bone layers were assumed. The temporomandibular joint was simplified to the elastic element to allow physiological movement of loaded bone. The muscles of mastication system were reduced to three pairs, modeled as shell structures. Finite element grid was created by the ANSYS software, where hexahedral and tetrahedral variants of SOLID185 element were used. A set of nonlinear contact conditions were applied on connecting devices and bone common surfaces. Properties of particular contact pair depend on screw - mini-plate connection type and possible gaps between fractured bone around osteosynthesis region. Some of the investigated cases contain prestress introduced to the mini-plate during the application, what responds the initial bending of the connecting device to fit the retromolar fossa region. Assumed bone fracture occurs within the mandible angle zone. Due to the significant deformation of the connecting plate in some of the assembly cases the elastic-plastic model of titanium alloy was assumed. The bone tissues were covered by the orthotropic material. As a loading were used the gauge force of magnitude of 100N applied in three different locations. Conducted analysis shows significant impact of mini-plate application methodology on the stress distribution within the miniplate. Prestress effect introduces additional loading, which leads to locally exceed the titanium alloy yield limit. Stress in surrounding bone increases rapidly around the screws application region, exceeding assumed bone yield limit, what indicate the local bone destruction. Approach with the doubled mini-plate shows increased stress within the connector due to the too rigid connection, where the main path of loading leads through the mini-plates instead of plates and connected bones. Clinical observations confirm more frequent plate destruction of stiffer connections. Some of them could be an effect of decreased low cyclic fatigue capability caused by the overloading. The executed analysis prove that the mini-plate system provides sufficient support to mandible fracture treatment, however, many applicable solutions shifts the entire system to the allowable material limits. The results show that connector application with the initial loading needs to be carefully established due to the small material capability tolerances. Comparison to the clinical observations allows optimizing entire connection to prevent future incidents.

Keywords: mandible fracture, mini-plate connection, numerical analysis, osteosynthesis

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789 Dietary Factors Contributing to Osteoporosis among Postmenopausal Women in Riyadh Armed Forces Hospital

Authors: Rabab Makki

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Bone mineral density and bone metabolism are affected by various factors such as genetic, endocrine, mechanical and nutritional. Our understanding of nutritional influences on bone health is limited because most studies have focused on calcium. This study investigated the dietary factors which are likely t contribute to Osteoporosis in Saudi post-menopausal women, and correlated it with BMD. This is a case controlled study involved 36 postmenopausal Saudi females selected from the Orthopedics and osteoporosis outpatient clinics, and 25 postmenopausal Saudi females as controls from the primary clinic of Military Hospital in Riyadh. The women were diagnosed as osteoporotic based on the BMD measurement at any site (left femur neck, right femur neck, left total hip or right total hip or spine). Both the controls and the Osteoporotics were over 50 years of age and BMI between 31-34 kg/m2 had 2nd degree obesity, and were not free from other problems such as diabetes, hypertension, etc. Subjects (osteoporotics and controls) were interviewed to called data on demographic characterstics, medical history, dietary intake anthropometry (height and weight) bone mineral density. Blood samples were collected from subjects (Osteoporotics and controls). Analysis of serum calcium, vitamin D, phosphate were done at the main laboratory at Military Hospital Riyadh, by the laboratory technician while BMD was determined at the department of Nuclear Medicine by an expert technician and results were interpreted by radiologist.Data on frequency of consumption of animal food (meat, eggs, poultry and fish) and diary foods (milk, yogurt, cheese) of osteoporotic was less than control. In spite of the low intake there was no association with BMD.In general, the vegetables and fruits were consumed less by the osteoporotics than control. The only fruit which had shown a significant positive correlation is banana with right and left hip BMD total probably due to high potassium and minerals content which likely to prevent bone resorption. Mataziz vegetables combination of wheat showed a significant positive correlation with the same site (total right and left hip). Both osteoporotics abd controls were consuming table sugar. (But the sweet intake showed a significant negative correlation with left neck femur BMD, suggesting sucrose increase urinary calcium loss. Both osteoporotic and controls were consuming Arabic coffee. A negative significant correlation between intake of Arabic coffee and BMD of right neck femur of osteoporosis patient was observed. It could be suggested that increased intake of fruits and vegetables, might promote bone density while high intake of coffee and sugars might affect bone density, no significant correlation was observed between BMD at any site and diary product. We can say the major risk factors are inadequate nutrition. Further studies are needed among Saudi population to confirm these results.

Keywords: osteoporosi, Saudia Arabia, Riyadh Armed Forces, postmenopausal women

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788 Instant Location Detection of Objects Moving at High Speed in C-OTDR Monitoring Systems

Authors: Andrey V. Timofeev

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The practical efficient approach is suggested to estimate the high-speed objects instant bounds in C-OTDR monitoring systems. In case of super-dynamic objects (trains, cars) is difficult to obtain the adequate estimate of the instantaneous object localization because of estimation lag. In other words, reliable estimation coordinates of monitored object requires taking some time for data observation collection by means of C-OTDR system, and only if the required sample volume will be collected the final decision could be issued. But it is contrary to requirements of many real applications. For example, in rail traffic management systems we need to get data off the dynamic objects localization in real time. The way to solve this problem is to use the set of statistical independent parameters of C-OTDR signals for obtaining the most reliable solution in real time. The parameters of this type we can call as 'signaling parameters' (SP). There are several the SP’s which carry information about dynamic objects instant localization for each of C-OTDR channels. The problem is that some of these parameters are very sensitive to dynamics of seismoacoustic emission sources but are non-stable. On the other hand, in case the SP is very stable it becomes insensitive as a rule. This report contains describing the method for SP’s co-processing which is designed to get the most effective dynamic objects localization estimates in the C-OTDR monitoring system framework.

Keywords: C-OTDR-system, co-processing of signaling parameters, high-speed objects localization, multichannel monitoring systems

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787 Effect of Varying Scaffold Architecture and Porosity of Calcium Alkali Orthophosphate Based-Scaffolds for Bone Tissue Engineering

Authors: D. Adel, F. Giacomini, R. Gildenhaar, G. Berger, C. Gomes, U. Linow, M. Hardt, B. Peleskae, J. Günster, A. Houshmand, M. Stiller, A. Rack, K. Ghaffar, A. Gamal, M. El Mofty, C. Knabe

Abstract:

The goal of this study was to develop 3D scaffolds from a silica containing calcium alkali orthophosphate utilizing two different fabrication processes, first a replica technique namely the Schwartzwalder Somers method (SSM), and second 3D printing, i.e. Rapid prototyping (RP). First, the mechanical and physical properties of the scaffolds (porosity, compressive strength, and solubility) was assessed and second their potential to facilitate homogenous colonization with osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture. To this end murine and rat calavarie osteoblastic cells were dynamically seeded on both scaffold types under perfusion with concentrations of 3 million cells. The amount of cells and extracellular matrix as well as osteogenic marker expression was evaluated using hard tissue histology, immunohistochemistry, and histomorphometric analysis. Total porosities of both scaffolds were 86.9 % and 50% for SSM and RP respectively, Compressive strength values were 0.46 ± 0.2 MPa for SSM and 6.6± 0.8 MPa for RP. Regarding the cellular behavior, RP scaffolds displayed a higher cell and matrix percentage of 24.45%. Immunoscoring yielded strong osteocalcin expression of cells and matrix in RP scaffolds and a moderate expression in SSM scaffolds. 3D printed RP scaffolds displayed superior mechanical and biological properties compared to SSM. 3D printed scaffolds represent excellent candidates for bone tissue engineering.

Keywords: calcium alkali orthophosphate, extracellular matrix mineralization, osteoblast differentiation, rapid prototyping, scaffold

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786 The Study of Periodontal Health Status in Menopausal Women with Osteoporosis Referred to Rheumatology Clinics in Yazd and Healthy People

Authors: Mahboobe Daneshvar

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Introduction: Clinical studies on the effect of systemic conditions on periodontal diseases have shown that some systemic deficiencies may provide grounds for the onset of periodontal diseases. One of these systemic problems is osteoporosis, which may be a risk factor for the onset and exacerbation of periodontitis. This study tends to evaluate periodontal indices in osteoporotic menopausal women and compare them with healthy controls. Materials and Methods: In this case-control study, participants included 45-75-year-old menopausal women referred to rheumatology wards of the Khatamolanbia Clinic and Shahid Sadoughi Hospital in Yazd; Their bone density was determined by DEXA-scan and by imaging the femoral-lumbar bone. Thirty patients with osteoporosis and 30 subjects with normal BMD were selected. Then, informed consent was obtained for participation in the study. During the clinical examinations, tooth loss (TL), plaque index (PI), gingival recession, pocket probing depth (PPD), clinical attachment loss (CAL), and tooth mobility (TM) were measured to evaluate the periodontal status. These clinical examinations were performed to determine the periodontal status by catheter, mirror and probe. Results: During the evaluation, there was no significant difference in PPD, PI, TM, gingival recession, and CAL between case and control groups (P-value>0.05); that is, osteoporosis has no effect on the above factors. These periodontal factors are almost the same in both healthy and patient groups. In the case of missing teeth, the following results were obtained: the mean of missing teeth was 22.173% of the total teeth in the case group and 18.583% of the total teeth in the control group. In the study of the missing teeth in the case and control groups, there was a significant relationship between case and control groups (P-value = 0.025). Conclusion: In fact, since periodontal disease is multifactorial and microbial plaque is the main cause, osteoporosis is considered a predisposing factor in exacerbation or persistence of periodontal disease. In patients with osteoporosis, usually pathological fractures, hormonal changes, and aging lead to reduced physical activity and affect oral health, which leads to the manifestation of periodontal disease. But this disease increases tooth loss by changing the shape and structure of bone trabeculae and weakening them. Osteoporosis does not seem to be a deterministic factor in the incidence of periodontal disease, since it affects bone quality rather than bone quantity.

Keywords: plaque index, Osteoporosis, tooth mobility, periodontal packet

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785 Physical Contact Modulation of Macrophage-Mediated Anti-Inflammatory Response in Osteoimmune Microenvironment by Pollen-Like Nanoparticles

Authors: Qing Zhang, Janak L. Pathak, Macro N. Helder, Richard T. Jaspers, Yin Xiao

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Introduction: Nanomaterial-based bone regeneration is greatly influenced by the immune microenvironment. Tissue-engineered nanomaterials mediate the inflammatory response of macrophages to regulate bone regeneration. Silica nanoparticles have been widely used in tissue engineering-related preclinical studies. However, the effect of topological features on the surface of silica nanoparticles on the immune response of macrophages remains unknown. Purposes: The aims of this research are to compare the influences of normal and pollen-like silica nano-surface topography on macrophage immune responses and to obtain insight into their potential regulatory mechanisms. Method: Macrophages (RAW 264.7 cells) were exposed to mesoporous silica nanoparticles with normal morphology (MSNs) and pollen-like morphology (PMSNs). RNA-seq, RT-qPCR, and LSCM were used to assess the changes in expression levels of immune response-related genes and proteins. SEM and TEM were executed to evaluate the contact and adherence of silica nanoparticles by macrophages. For the assessment of the immunomodulation-mediated osteogenic potential, BMSCs were cultured with conditioned medium (CM) from LPS pre-stimulated macrophage cultures treated with MSNs or PMSNs. Osteoimmunomodulatory potential of MSNs and PMSNs in vivo was tested in a mouse cranial bone osteolysis model. Results: The results of the RNA-seq, RT-qPCR, and LSCM assays showed that PMSNs inhibited the expression of pro-inflammatory genes and proteins in macrophages. SEM images showed distinct macrophage membrane surface binding patterns of MSNs and PMSNs. MSNs were more evenly dispersed across the macrophage cell membrane, while PMSNs were aggregated. PMSNs-induced macrophage anti-inflammatory response was associated with upregulation of the cell surface receptor CD28 and inhibition of ERK phosphorylation. TEM images showed that both MSNs and PMSNs could be phagocytosed by macrophages, and inhibiting nanoparticle phagocytosis did not affect the expression of anti-inflammatory genes and proteins. Moreover, PMSNs-induced conditioned medium from macrophages enhanced BMP-2 expression and osteogenic differentiation mBMSCs. Similarly, PMSNs prevented LPS-induced bone resorption via downregulation of inflammatory reaction. Conclusions: PMSNs can promote bone regeneration by modulating osteoimmunological processes through surface topography. The study offers insights into how surface physical contact cues can modulate the regulation of osteoimmunology and provides a basis for the application of nanoparticles with pollen-like morphology to affect immunomodulation in bone tissue engineering and regeneration.

Keywords: physical contact, osteoimmunology, macrophages, silica nanoparticles, surface morphology, membrane receptor, osteogenesis, inflammation

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784 Comparison of Bone Mineral Density of Lumbar Spines between High Level Cyclists and Sedentary

Authors: Mohammad Shabani

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The physical activities depending on the nature of the mechanical stresses they induce on bone sometimes have brought about different results. The purpose of this study was to compare bone mineral density (BMD) of the lumbar spine between the high-level cyclists and sedentary. Materials and Methods: In the present study, 73 cyclists senior (age: 25.81 ± 4.35 years; height: 179.66 ± 6.31 cm; weight: 71.55 ± 6.31 kg) and 32 sedentary subjects (age: 28.28 ± 4.52 years; height: 176.56 ± 6.2 cm; weight: 74.47 ± 8.35 kg) participated voluntarily. All cyclists belonged to the different teams from the International Cycling Union and they trained competitively for 10 years. BMD of the lumbar spine of the subjects was measured using DXA X-ray (Lunar). Descriptive statistics calculations were performed using computer software data processing (Statview 5, SAS Institute Inc. USA). The comparison of two independent distributions (BMD high level cyclists and sedentary) was made by the Student T Test standard. Probability 0.05 (p≤0 / 05) was adopted as significance. Results: The result of this study showed that the BMD values of the lumbar spine of sedentary subjects were significantly higher for all measured segments. Conclusion and Discussion: Cycling is firstly a common sport and on the other hand endurance sport. It is now accepted that weight bearing exercises have an osteogenic effect compared to non-weight bearing exercises. Thus, endurance sports such as cycling, compared to the activities imposing intense force in short time, seem not to really be osteogenic. Therefore, it can be concluded that cycling provides low stimulates osteogenic because of specific biomechanical forces of the sport and its lack of impact.

Keywords: BMD, lumbar spine, high level cyclist, cycling

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783 RNAseq Reveals Hypervirulence-Specific Host Responses to M. tuberculosis Infection

Authors: Gina Leisching, Ray-Dean Pietersen, Carel Van Heerden, Paul Van Helden, Ian Wiid, Bienyameen Baker

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The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analyzed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow-derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M. tuberculosis clinical isolate. RNAseq revealed 69 differentially expressed host genes in BMDMs during comparison of these two transcriptomes. Pathway analysis revealed activation of the stress-induced and growth inhibitory Gadd45 signaling pathway in hypervirulent infected BMDMs. Upstream regulators of interferon activation such as and IRF3 and IRF7 were predicted to be upregulated in hypovirulent-infected BMDMs. Additional analysis of the host immune response through ELISA and qPCR included the use of human THP-1 macrophages where a robust proinflammatory response was observed after infection with the hypervirulent strain. RNAseq revealed two early-response genes (IER3 and SAA3) and two host-defence genes (OASL1 and SLPI) that were significantly upregulated by the hypervirulent strain. The role of these genes under M.tb infection conditions are largely unknown but here we provide validation of their presence with use of qPCR and Western blot. Further analysis into their biological role under infection with virulent M.tb is required.

Keywords: host-response, Mycobacterium tuberculosis, RNAseq, virulence

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782 Preliminary Design, Production and Characterization of a Coral and Alginate Composite for Bone Engineering

Authors: Sthephanie A. Colmenares, Fabio A. Rojas, Pablo A. Arbeláez, Johann F. Osma, Diana Narvaez

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The loss of functional tissue is a ubiquitous and expensive health care problem, with very limited treatment options for these patients. The golden standard for large bone damage is a cadaveric bone as an allograft with stainless steel support; however, this solution only applies to bones with simple morphologies (long bones), has a limited material supply and presents long term problems regarding mechanical strength, integration, differentiation and induction of native bone tissue. Therefore, the fabrication of a scaffold with biological, physical and chemical properties similar to the human bone with a fabrication method for morphology manipulation is the focus of this investigation. Towards this goal, an alginate and coral matrix was created using two production techniques; the coral was chosen because of its chemical composition and the alginate due to its compatibility and mechanical properties. In order to construct the coral alginate scaffold the following methodology was employed; cleaning of the coral, its pulverization, scaffold fabrication and finally the mechanical and biological characterization. The experimental design had: mill method and proportion of alginate and coral, as the two factors, with two and three levels each, using 5 replicates. The coral was cleaned with sodium hypochlorite and hydrogen peroxide in an ultrasonic bath. Then, it was milled with both a horizontal and a ball mill in order to evaluate the morphology of the particles obtained. After this, using a combination of alginate and coral powder and water as a binder, scaffolds of 1cm3 were printed with a SpectrumTM Z510 3D printer. This resulted in solid cubes that were resistant to small compression stress. Then, using a ESQUIM DP-143 silicon mold, constructs used for the mechanical and biological assays were made. An INSTRON 2267® was implemented for the compression tests; the density and porosity were calculated with an analytical balance and the biological tests were performed using cell cultures with VERO fibroblast, and Scanning Electron Microscope (SEM) as visualization tool. The Young’s moduli were dependent of the pulverization method, the proportion of coral and alginate and the interaction between these factors. The maximum value was 5,4MPa for the 50/50 proportion of alginate and horizontally milled coral. The biological assay showed more extracellular matrix in the scaffolds consisting of more alginate and less coral. The density and porosity were proportional to the amount of coral in the powder mix. These results showed that this composite has potential as a biomaterial, but its behavior is elastic with a small Young’s Modulus, which leads to the conclusion that the application may not be for long bones but for tissues similar to cartilage.

Keywords: alginate, biomaterial, bone engineering, coral, Porites asteroids, SEM

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781 Bioinformatic Prediction of Hub Genes by Analysis of Signaling Pathways, Transcriptional Regulatory Networks and DNA Methylation Pattern in Colon Cancer

Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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780 The Functional Rehabilitation of Peri-Implant Tissue Defects: A Case Report

Authors: Özgür Öztürk, Cumhur Sipahi, Hande Yeşil

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Implant retained restorations commonly consist of a metal-framework veneered with ceramic or composite facings. The increasing and expanding use of indirect resin composites in dentistry is a result of innovations in materials and processing techniques. Of special interest to the implant restorative field is the possibility that composites present significantly lower peak vertical and transverse forces transmitted at the peri-implant level compared to metal-ceramic supra structures in implant-supported restorations. A 43-year-old male patient referred to the department of prosthodontics for an implant retained fixed prosthesis. The clinical and radiographic examination of the patient demonstrated the presence of an implant in the right mandibular first molar tooth region. A considerable amount of marginal bone loss around the implant was detected in radiographic examinations combined with a remarkable peri-implant soft tissue deficiency. To minimize the chewing loads transmitted to the implant-bone interface it was decided to fabricate an indirect composite resin veneered single metal crown over a screw-retained abutment. At the end of the treatment, the functional and aesthetic deficiencies were fully compensated. After a 6 months clinical and radiographic follow-up period the not any additional pathologic invasion was detected in the implant-bone interface and implant retained restoration did not reveal any vehement complication.

Keywords: dental implant, fixed partial dentures, indirect composite resin, peri-implant defects

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779 Additive Manufacturing of Titanium Metamaterials for Tissue Engineering

Authors: Tuba Kizilirmak

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Distinct properties of porous metamaterials have been largely processed for biomedicine requiring a three-dimensional (3D) porous structure engaged with fine mechanical features, biodegradation ability, and biocompatibility. Applications of metamaterials are (i) porous orthopedic and dental implants; (ii) in vitro cell culture of metamaterials and bone regeneration of metamaterials in vivo; (iii) macro-, micro, and nano-level porous metamaterials for sensors, diagnosis, and drug delivery. There are some specific properties to design metamaterials for tissue engineering. These are surface to volume ratio, pore size, and interconnection degrees are selected to control cell behavior and bone ingrowth. In this study, additive manufacturing technique selective laser melting will be used to print the scaffolds. Selective Laser Melting prints the 3D components according to designed 3D CAD models and manufactured materials, adding layers progressively by layer. This study aims to design metamaterials with Ti6Al4V material, which gives benefit in respect of mechanical and biological properties. Ti6Al4V scaffolds will support cell attachment by conferring a suitable area for cell adhesion. This study will control the osteoblast cell attachment on Ti6Al4V scaffolds after the determination of optimum stiffness and other mechanical properties which are close to mechanical properties of bone. Before we produce the samples, we will use a modeling technique to simulate the mechanical behavior of samples. These samples include different lattice models with varying amounts of porosity and density.

Keywords: additive manufacturing, titanium lattices, metamaterials, porous metals

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778 Children Asthma; The Role of Molecular Pathways and Novel Saliva Biomarkers Assay

Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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777 Management of Femoral Neck Stress Fractures at a Specialist Centre and Predictive Factors to Return to Activity Time: An Audit

Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey

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Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.

Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D

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776 Biocompatible Beta Titanium Alloy Ti36Nb6Ta as a Suitable Material for Bone Regeneration

Authors: Vera Lukasova, Eva Filova, Jana Dankova, Vera Sovkova, Matej Daniel, Michala Rampichova

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Proper bone implants should promote fast adhesion of cells, stimulate cell differentiation and support the formation of bone tissue. Nowadays titanium is used as a biocompatible material capable of bone tissue integration. This study was focused on comparison of bioactive properties of two titanium alloys - beta titanium alloy Ti36Nb6Ta and standard medical titanium alloy Ti6A14V. The advantage of beta titanium alloy Ti36Nb6Ta is mainly that this material does not contain adverse elements like vanadium or aluminium. Titanium alloys were sterilized in ethanol, placed into 48 well plates and seeded with porcine mesenchymal stem cells. Cells were cultivated for 14 days in standard growth cultivation media with osteogenic supplements. Cell metabolic activity was quantified using MTS assay (Promega). Cell adhesion on day 1 and cell proliferation on further days were verified immunohistochemically using beta-actin monoclonal antibody and secondary antibody conjugated with AlexaFluor®488. Differentiation of cells was evaluated using alkaline phosphatase assay. Additionally, gene expression of collagen I was measured by qRT-PCR. Porcine mesenchymal stem cells adhered and spread well on beta titanium alloy Ti36Nb6Ta on day 1. During the 14 days’ time period the cells were spread confluently on the surface of the beta titanium alloy Ti36Nb6Ta. The metabolic activity of cells increased during the whole cultivation period. In comparison to standard medical titanium alloy Ti6A14V, we did not observe any differences. Moreover, the expression of collagen I gene revealed no statistical differences between both titanium alloys. Therefore, a beta titanium alloy Ti36Nb6Ta promotes cell adhesion, metabolic activity, proliferation and collagen I expression equally to standard medical titanium alloy Ti6A14V. Thus, beta titanium is a suitable material that provides sufficient biocompatible properties. This project was supported by the Czech Science Foundation: grant No. 16-14758S.

Keywords: beta titanium alloy, biocompatibility, differentiation, mesenchymal stem cells

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775 “SockGEL/PLUG” Injectable Smart/Intelligent and Bio-Inspired Sol-Gel Nanomaterials for Simple and Complex Oro-Dental and Cranio-Maxillo-Facial Interventional Applications

Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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774 Evaluation of the Efficacy of Titanium Alloy Dental Implants Coated by Bio-ceramic Apatite Wollastonite (Aw) and Hydroxyapatite (Ha) by Pulsed Laser Deposition

Authors: Betsy S. Thomas, Manjeet Marpara, K. M. Bhat

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Introduction: After the initial enthusiasm and interest in hydroxyapatite products subsided due to dissolution of the coating and failure at the coating interface, this was a unique attempt to create a next generation of dental implant. Materials and Methods: The adhesion property of AW and HA coatings at various temperature by pulsed laser deposition was assessed on titanium plates. Moreover, AW/HA coated implants implanted in the femur of the rabbits was evaluated at various intervals. Results: Decohesion load was more for AW in scratch test and more bone formation around AW coated implants on histological evaluation. Discussion: AW coating by pulsed laser deposition was more adherent to the titanium surface and led to faster bone formation than HA. Conclusion: This experiment opined that AW coated by pulsed laser deposition seems to be a promising method in achieving bioactive coatings on titanium implants.

Keywords: surface coating, dental implants, osseo integration, biotechnology

Procedia PDF Downloads 359