Search results for: bone metastases

Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Fedor Semenov

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One of the most widespread facial bones’ malformations – the congenital palatoschisis – significant impact on drainage and ventilation of the middle ear through the incorrect work of soft palate muscles, which results in recurrent middle ear inflammation and subsequently leads to the hearing dysfunction. The purpose of this research is to evaluate the auditory tube function and hearing condition before the operative treatment (uranoplasty) and after 3 and 12 months. 42 patients aged from 6 months to 17 years who had soft and hard palate cleft and B and C type tympanogram were included in that study. The examination includes otoscopy, pure tone audiometry (for patients older than 8 years – 11 patients), tympanometry. According to the otoscopy results all the patients were divided into two groups: those who had a retracted eardrum and those who had a normal one. The results of pure tone audiometry showed that there were six patients with an air-bone gap of more than 10 dB and the five with normal audiograms. According to the results of this research, uranoplasty demonstrated strongly positive effects on the auditory tube function: normalization of eardrum view upon otoscopy was observed in 64% of children with a retracted eardrum three month after surgery and 85 % twelve months. The quantity of patients with A-type of tympanogram improved in 25 children out of 41 in 3 month and in 35 out of 41 in twelve months after operation. While before the operative treatment, six patients older than 8 years had had an air-bone gap of more than 10 dB; only two of them still had it in 12 months, and the others’ audiograms were normal. To sum it up, the uranoplasty showed a significant contribution in the restoration of auditory tube functioning. Some patients had signs of auditory dysfunction even after the operative treatment. That group of children needs further treatment by an otorhinolaryngologist.

Keywords: auditory tube dysfunction, palatoschisis, uranoplasy, otitis

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Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

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Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

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Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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Authors: A. Drapeaux, S. Aviles, E. Garfoot

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Stem cell injections are a promising alternative treatment for hip osteoarthritis. Current literature has focused on short-term outcomes for both knee and hip osteoarthritis; however, there is a significant gap for longitudinal benefits for hip OA and limited firm conclusions due to small sample sizes. The purpose of this prospective study was to determine longitudinal changes in pain, function, and radiographs following bone marrow concentrate injection (BMAC) into the osteoarthritic hip joint. Methods: A prospective, cross-sectional study was conducted over the course of 12 months at an orthopedic practice. The study recruited 15 osteoarthritic pre-surgical hips with mild to moderate osteoarthritic severity who were scheduled to undergo hip arthroscopy. Data was collected at both pre-operative and post-operative time frames. Data collected included: hip radiographs, i-HOT-33 questionnaire data, BMAC autologous volume, and demographics. Questionnaire data was captured using Qualtrics XM software, and participants were sent an anonymous link at the following time frames: pre-operative, 2 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and 24 months. Radiographic changes and BMAC volume were collected and reviewed by an orthopedic surgeon and sent to the primary investigator. Data was exported and analyzed in IBM-SPSS. Results: A total of 15 hips from 15 participants (mean age: 49, gender: 50% males, 50% females, BMI: 29.7) were used in the final analysis. Summative i-HOT 33 mean scores significantly changed between pre-operative status and 2-6 weeks post-operative status (p <.001) and pre-operative status and 3-6 months post-operative status (p <.001). There were no significant changes between other post-operative phases or between pre-operative status and 12 months post-operative. Significant improvements were found between summative i-HOT 33 mean (p<.001), daily pain (p<.001), daily sitting (p=.02), daily distance walked (p =.003), and daily limp (p=0.03) and post-operative status (2-6 weeks). No significant differences between demographic variables (gender, age, tobacco use, or diabetes) and i-HOT 33 summative mean scores. Discussion/Implications: The purpose of this study was to determine longitudinal changes in pain and function following a hip joint bone marrow concentrate injection. Results indicate that participants experience a significant improvement in pain and function between pre-operative and 2-6 weeks and 3-6 months post-injection. Participants also self-reported a significant change in average daily pain with sitting and walking between pre-operation and 2-6 weeks post-operative. This study includes a larger sample size of hip osteoarthritis cases; however, future research is warranted to include random controlled trials with a larger sample size.

Keywords: adult stem cell, orthopedics, osteoarthritis (hip), patient outcome assessment

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Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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Authors: Sergey N. Ermoliev, Margarita A. Belousova, Aida D. Goncharenko

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Application of the diagnostic complex of highly informative functional methods (electromyography, reodentography, laser Doppler flowmetry, reoperiodontography, vital computer capillaroscopy, optical tissue oximetry, laser fluorescence diagnosis) allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment. Introduction. It is necessary to create a complex of innovative highly informative and safe functional diagnostic methods for improvement of the quality of patient treatment by the early detection of stomatologic diseases. The purpose of the present study was to investigate the etiology and pathogenesis of functional disorders identified in the pathology of hard tissue, dental pulp, periodontal, oral mucosa and chewing function, and the creation of new approaches to the diagnosis of dental diseases. Material and methods. 172 patients were examined. Density of hard tissues of the teeth and jaw bone was studied by intraoral ultrasonic densitometry (USD). Electromyographic activity of masticatory muscles was assessed by electromyography (EMG). Functional state of dental pulp vessels assessed by reodentography (RDG) and laser Doppler flowmetry (LDF). Reoperiodontography method (RPG) studied regional blood flow in the periodontal tissues. Microcirculatory vascular periodontal studied by vital computer capillaroscopy (VCC) and laser Doppler flowmetry (LDF). The metabolic level of the mucous membrane was determined by optical tissue oximetry (OTO) and laser fluorescence diagnosis (LFD). Results and discussion. The results obtained revealed changes in mineral density of hard tissues of the teeth and jaw bone, the bioelectric activity of masticatory muscles, regional blood flow and microcirculation in the dental pulp and periodontal tissues. LDF and OTO methods estimated fluctuations of saturation level and oxygen transport in microvasculature of periodontal tissues. With LFD identified changes in the concentration of enzymes (nicotinamide, flavins, lipofuscin, porphyrins) involved in metabolic processes Conclusion. Our preliminary results confirmed feasibility and safety the of intraoral ultrasound densitometry technique in the density of bone tissue of periodontium. Conclusion. Application of the diagnostic complex of above mentioned highly informative functional methods allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment.

Keywords: electromyography (EMG), reodentography (RDG), laser Doppler flowmetry (LDF), reoperiodontography method (RPG), vital computer capillaroscopy (VCC), optical tissue oximetry (OTO), laser fluorescence diagnosis (LFD)

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Authors: Antonio Monteiro, Jorge Azevedo, Severiano Silva, Alfredo Teixeira

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The objective of this study was to compare the carcass and in vivo real-time ultrasound measurements (RTU) and their capacity to predict the composition of Serrana goats up to 40% of maturity. Twenty one females (11.1 ± 3.97 kg) and Twenty one males (15.6 ± 5.38 kg) were utilized to made in vivo measurements with a 5 MHz probe (ALOKA 500V scanner) at the 9th-10th, 10th-11th thoracic vertebrae (uT910 and uT1011, respectively), at the 1st- 2nd, 3rd-4th, and 4th-5th lumbar vertebrae (uL12, ul34 and uL45, respectively) and also at the 3rd-4th sternebrae (EEST). It was recorded the images of RTU measurements of Longissimus thoracis et lumborum muscle (LTL) depth (EM), width (LM), perimeter (PM), area (AM) and subcutaneous fat thickness (SFD) above the LTL, as well as the depth of tissues of the sternum (EEST) between the 3rd-4th sternebrae. All RTU images were analyzed using the ImageJ software. After slaughter, the carcasses were stored at 4 ºC for 24 h. After this period the carcasses were divided and the left half was entirely dissected into muscle, dissected fat (subcutaneous fat plus intermuscular fat) and bone. Prior to the dissection measurements equivalent to those obtained in vivo with RTU were recorded. Using the Statistica 5, correlation and regression analyses were performed. The prediction of carcass composition was achieved by stepwise regression procedure, with live weight and RTU measurements with and without transformation of variables to the same dimension. The RTU and carcass measurements, except for SFD measurements, showed high correlation (r > 0.60, P < 0.001). The RTU measurements and the live weight, showed ability to predict carcass composition on muscle (R2 = 0.99, P < 0.001), subcutaneous fat (R2 = 0.41, P < 0.001), intermuscular fat (R2 = 0.84, P < 0.001), dissected fat (R2 = 0.71, P < 0.001) and bone (R2 = 0.94, P < 0.001). The transformation of variables allowed a slight increase of precision, but with the increase in the number of variables, with the exception of subcutaneous fat prediction. In vivo measurements by RTU can be applied to predict kid goat carcass composition, from 5 measurements of RTU and the live weight.

Keywords: carcass, goats, real time, ultrasound

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Authors: Mona Vijayaran, Gurleen Oberoi, Sanjay Mishra

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Introduction: p190 BCR‐ABL1 in CML is often associated with monocytosis. In the case described here, monocytosis is associated with coexisting p210 BCR‐ABL and CMML clones. Mutation analysis using next‐generation sequence (NGS) in our case showed TET2 and SRSF2 mutations. Aims & Objectives: A 75-year male was evaluated for monocytosis and thrombocytopenia. CBC showed Hb-11.8g/dl, TLC-12,060/cmm, Monocytes-35%, Platelets-39,000/cmm. Materials & Methods: Bone marrow examination showed a hypercellular marrow with myeloid series showing sequential maturation up to neutrophils with 30% monocytes. Immunophenotyping by flow cytometry from bone marrow had 3% blasts. Making chronic myelomonocytic leukemia as the likely diagnosis. NGS for myeloid mutation panel had TET2 (48.9%) and SRSF2 (32.5%) mutations. This report further supported the diagnosis of CMML. To fulfil the WHO diagnostic criteria for CMML, a BCR ABL1 by RQ-PCR was sent. The report came positive for p210 (B3A2, B2A2) Major Transcript (M-BCR) % IS of 38.418. Result: The patient was counselled regarding the unique presentation of the presence of 2 clones- P210 CML and CMML. After discussion with an international faculty with vast experience in CMML. It was decided to start this elderly gentleman on Imatinib 200mg and not on azacytidine, as ASXL1 was not present; hence, his chances of progressing to AML would be less and on the other end, if CML is left untreated then chances of progression to blast phase would always be a possibility. After 3 months on Imatinib his platelet count improved to 80,000 to 90,000/cmm, but his monocytosis persists. His 3rd month BCR-ABL1 IS% is 0.004%. Conclusion: After searching the literature, there were no case reports of a coexisting CML p210 with CMML. This case might be the first case report. p190 BCR ABL1 is often associated with monocytosis. There are few case reports of p210 BCR ABL1 positivity in patients with monocytosis but none with coexisting CMML. This case highlights the need for extensively evaluating patients with monocytosis with next-generation sequencing for myeloid mutation panel and BCR-ABL1 by RT-PCR to correctly diagnose and treat them.

Keywords: CMML, NGS, p190 CML, Imatinib

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Background and Objective: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing an infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Shahid Ghazi Tabatabaei Hospital, Tabriz, Iran. Subjects and Methods: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. Methods: Patients with febrile neutropenia between 2015 and 2018 were retrospectively evaluated regarding their infection profile and associated risk factors. This survey included: bacterial culture and blood culture on specific media. Results: Infection occurred in 57.2% of 56 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9%). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status, and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1%) in the study sample. Conclusion: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary.

Keywords: hematopoietic stem cell, autologous bone marrow transplantation, infection profile, tabriz, Iran

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Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

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Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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Authors: Nan Deng, Zhenqiu Liu

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Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.

Keywords: bioinformatics, cancer, convolutional neural network, deep leaning, gene expression pattern

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Authors: M. Abuqebitah, H. Tanyildizi, N. Yeyin, I. Cavdar, M. Demir, L. Kabasakal

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Aim: Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for wide range of cancers. Presently dosimetry is highly required either to plan treatment or to ascertain the absorbed dose delivered to critical organs during treatment. Methods and Materials: The study comprised 7 patients suffered from prostate cancer with progressive disease and candidate to undergo Lu-177-DOTA-617 therapy following to PSMA- PET/CT imaging for all patients. (5.2±0.3 mCi) was intravenously injected. To evaluate bone marrow absorbed dose 2 cc blood samples were withdrawn in short variable times (3, 15, 30, 60, 180 minutes) after injection. Furthermore, whole body scans were performed using scintillation gama camera in 4, 24, 48, and 120 hours after injection and in order to quantify the activity taken up in the body, kidneys , liver, right parotid, and left parotid the geometric mean of anterior and posterior counts were determined through ROI analysis, after that background subtraction and attenuation correction were applied using patients PSMA- PET/CT images taking in a consideration: organ thickness, body thickness, and Hounsfield unites from CT scan. OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Findings: Absorbed doses of bone marrow, left kidney, right kidney, liver, left parotid, right parotid, total body were 1.28±0.52, 32.36±16.36, 32.7±13.68, 10.35±3.45, 38.67±21.29, 37.55±19.77, 2.25±0.95 (mGy/mCi), respectively. Conclusion: Our first results clarify that Lu-177-DOTA-617 is safe and reliable therapy as there were no complications seen. In the other hand, the observable variation in the absorbed dose of the critical organs among the patients necessitate patient-specific dosimetry approach to save body organs and particularly highly exposed kidneys and parotid gland.

Keywords: Lu-177-PSMA, prostate cancer, radionuclide therapy

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Rezvan Hosseinian

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Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. The correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. The median age (IQR) was 47.0 years (16), and 52% had a diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) were associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of the distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low hematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: disease subsets, hand radiography, joint erosion, sclerosis

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Authors: Nasrin Azarbani

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Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. Correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. Median age (IQR) was 47.0 years (16), and 52% had diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) was associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low haematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: sclerosis, disease subsets, joint erosion, musculoskeletal

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Authors: Ivone R. Oliveira, Isabela S. Gonçalves, Tiago M. B. Campos, Leandro J. Raniero, Luana M. R. Vasconcellos, João H. Lopes

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Originally, the principles of guided tissue/bone regeneration (GTR/GBR) were followed to restore the architecture and functionality of the periodontal system. In essence, a biocompatible polymer-based occlusive membrane is used as a barrier to prevent migration of epithelial and connective tissue to the regenerating site. In this way, progenitor cells located in the remaining periodontal ligament can recolonize the root area and differentiate into new periodontal tissues, alveolar bone, and new connective attachment. The use of synthetic or collagen-derived membranes with or without calcium phosphate-based bone graft materials has been the treatment used. Ideally, these membranes need to exhibit sufficient initial mechanical strength to allow handling and implantation, withstand the various mechanical stresses suffered during surgery while maintaining their integrity, and support the process of bone tissue regeneration and repair by resisting cellular traction forces and wound contraction forces during tissue healing in vivo. Although different RTG/ROG products are available on the market, they have serious deficiencies in terms of mechanical strength. Aiming to improve the mechanical strength and osteogenic properties of the membrane, this work evaluated the production of membranes that integrate the biocompatibility of the natural polymer (silk fibroin - FS) and the synthetic polymer poly(vinyl pyrrolidone - PVP) with graphene nanoplates (NPG) and gold nanoparticles (AuNPs), using the electrospinning equipment (AeroSpinner L1.0 from Areka) which allows the execution of high voltage spinning and/or solution blowing and with a high production rate, enabling development on an industrial scale. Silk fibroin uniquely solved many of the problems presented by collagen and was used in this work because it has unique combined merits, such as programmable biodegradability, biocompatibility and sustainable large-scale production. Graphene has attracted considerable attention in recent years as a potential biomaterial for mechanical reinforcement because of its unique physicochemical properties and was added to improve the mechanical properties of the membranes associated or not with the presence of AuNPs, which have shown great potential in regulating osteoblast activity. The preparation of FS from silkworm cocoons involved cleaning, degumming, dissolution in lithium bromide, dialysis, lyophilization and dissolution in hexafluoroisopropanol (HFIP) to prepare the solution for electrospinning, and crosslinking tests were performed in methanol. The NPGs were characterized and underwent treatment in nitric acid for functionalization to improve the adhesion of the nanoplates to the PVP fibers. PVP-NPG membranes were produced with 0.5, 1.0 and 1.5 wt% functionalized or not and evaluated by SEM/FEG, FTIR, mechanical strength and cell culture assays. Functionalized GNP particles showed stronger binding, remaining adhered to the fibers. Increasing the graphene content resulted in higher mechanical strength of the membrane and greater biocompatibility. The production of FS-PVP-NPG-AuNPs hybrid membranes was performed by electrospinning in separate syringes and simultaneously the FS solution and the solution containing PVP-NPG 1.5 wt% in the presence or absence of AuNPs. After cross-linking, they were characterized by SEM/FEG, FTIR and behavior in cell culture. The presence of NPG-AuNPs increased the viability and the presence of mineralization nodules.

Keywords: barrier membranes, silk fibroin, nanoparticles, tissue regeneration.

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Authors: Osama Shakeel

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The objective of the paper is to study the clinic-pathological factors, survival analyses, recurrence rate, metastatic rate, risk factors and the management of cutaneous malignant melanoma at Shaukat Khanum Memorial Cancer Hospital and Research Center. Methodology: From 2014 to 2017, all patients with a diagnosis of cutaneous malignant melanoma (CMM) were included in the study. Demographic variables were collected. Short and long term oncological outcomes were recorded. All data were entered and analyzed in SPSS version 21. Results: A total of 28 patients were included in the study. Median age was 46.5 +/-15.9 years. There were 16 male and 12 female patients. The family history of melanoma was present in 7.1% (n=2) of the patients. All patients had a mean survival of 13.43+/- 9.09 months. Lower limb was the commonest site among all which constitutes 46.4%(n=13). On histopathological analyses, ulceration was seen in 53.6% (n=15) patients. Unclassified tumor type was present in 75%(n=21) of the patients followed by nodular 21.4% (n=6) and superficial spreading 3.5%(n=1). Clark level IV was the commonest presentation constituting 46.4%(n=13). Metastases were seen in 50%(n=14) of the patients. Local recurrence was observed in 60.7%(n=17). 64.3%(n=18) lived after one year of treatment. Conclusion: CMM is a fatal disease. Although its disease of fair skin individuals, however, the incidence of CMM is also rising in this part of the world. Management includes early diagnoses and prompt management. However, mortality associated with this disease is still not favorable.

Keywords: malignant cancer of skin, cutaneous malignant melanoma, skin cancer, survival analyses

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Authors: Ilja Käch, Abdul R. Jandali, Nadja Zechmann-Müller

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Introduction: We discuss the treatment of two young male patients suffering from scaphoid non-union after a traumatic scaphoid fracture. The currently propagated techniques for treating a scaphoid non-union in children are either the operative reconstruction of the scaphoid or the conservative treatment with splinting in a scaphoid cast. Cases: In the first case, we operated on a 13 years old male patient with a posttraumatic scaphoid non-union in the middle third with a humpback deformity. We resected the middle third of the scaphoid and grafted the defect with an iliac crest bone, and the DISI-Deformity was reduced. Fixation was performed with K-Wires and immobilisation in a scaphoid cast. In the second case a 13 years old male patient also with a posttraumatic scaphoid non-union in the middle third and humpback deformity, DISI-deformity, was treated conservatively. Immobilisation in a scaphoid cast for four months was performed. Results: Operative: One year postoperatively the patient achieved a painless free arc of motion. Flexion/Extension 70/0/60°, Radial-/Ulnarduction 30/0/30° and Pro-/Supination 90/0/90°. The computer tomogram showed complete consolidation and bony fusion of the iliac crest bone. Conservative: Six to eight months after conservative treatment the patient demonstrated painless motion and AROM Flexion/Extension 80/0/80°, Radial-/Ulnarduction and Pro-/Supination in maximum range. Complete consolidation in the computer tomogram with persistent humpback- and DISI deformity. Conclusion: In the literature, both techniques are described, either the operative scaphoid reconstruction or the conservative treatment with splinting. In our cases, both the operative and conservative treatments showed comparable good results. However, the humpback- and DISI deformity can only be addressed with a surgical approach.

Keywords: scaphoid, non-union, trauma, operative vs. non operative

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Authors: Jasmina Pluncevic Gligoroska, Sanja Manchevska, Vaska Antevska, Lidija Todorovska, Beti Dejanova, Sunchica Petrovska, Ivanka Karagjozova, Elizabeta Sivevska

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Introduction: Anthropometric measurements are integral part of regular medical examinations of athletes. In addition to the quantification of the size of the body, these measurements indicate the quality of the physical status, because of its association with sports performance. The purpose of this study was to examine whether there are differences in anthropometric parameters and body mass components in female athletes who participate in two different types of sports. Methods: A total of 27 athletes, 15 handball players and 12 basketball players, at the average age of 22.7 years (age span from 17 to 30 years) entered the study. Anthropometric method by Matiegka was used for determination of body components. Sixteen anthropometric measures were taken: height, weight, four diameters of joints, four circumferences of limbs and six skin folds. Results: Handball players were 169.6±6.7 cm tall and 63,75±7.5 kg heavy. Their average relative muscle mass (absolute mass in kg) was 51% (32.5kg), while bone component was 16.8% (10.7kg) and fat component was 14.3% (7.74kg). The basketball players were 177.4±8.2cm tall and 70.37±12.1kg heavy. Their average relative muscle mass (absolute mass in kg) was 51.9 % (36.6kg), bone component was 16.37% (11.5kg) and fat component was 15.36% (9.4kg). The comparison of anthropometric values showed that basketball players were statistically significantly higher and heavier than handball players (p<0.05). Statistically significant difference (p<0.05) was observed in the range of upper leg circumference (higher in basketball players) and the forearm skin fold (higher in the basketball players). Conclusion: Handball players and basketball players significantly differed in basic anthropometric measures (height and weight), but the body components had almost identical values. The anthropometric measurements that have been taken did not show significant difference between handball and basketball female players despite the different physical demands of the games.

Keywords: anthropometry, body components, basketball, handball female players

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Authors: Pabitra Sahu, M. Manohari, S. Priyadharshini, R. Santhanam, S. Chandrasekaran, B. Venkatraman

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Radiation workers of reprocessing plants have a potential for internal exposure due to actinides and fission products. Radionuclides like Americium, lead, Polonium and Europium are bone seekers and get accumulated in the skeletal part. As the major skeletal content is in the skull (13%) and knee (22%), measurements of old intake have to be carried out in the skull and knee. At the Indira Gandhi Centre for Atomic Research, a twin HPGe-based actinide monitor is used for the measurement of actinides present in bone. Efficiency estimation, which is one of the prerequisites for the quantification of radionuclides, requires anthropomorphic phantoms. Such phantoms are very limited. Hence, in this study, efficiency curves for a Twin HPGe-based actinide monitoring system are established theoretically using the FLUKA Monte Carlo method and ICRP adult male voxel phantom. In the case of skull measurement, the detector is placed over the forehead, and for knee measurement, one detector is placed over each knee. The efficiency values of radionuclides present in the knee and skull vary from 3.72E-04 to 4.19E-04 CPS/photon and 5.22E-04 to 7.07E-04 CPS/photon, respectively, for the energy range 17 to 3000keV. The efficiency curves for the measurement are established, and it is found that initially, the efficiency value increases up to 100 keV and then starts decreasing. It is found that the skull efficiency values are 4% to 63% higher than that of the knee, depending on the energy for all the energies except 17.74 keV. The reason is the closeness of the detector to the skull compared to the knee. But for 17.74 keV the efficiency of the knee is more than the skull due to the higher attenuation caused in the skull bones because of its greater thickness. The Minimum Detectable Activity (MDA) for 241Am present in the skull and knee is 9 Bq. 239Pu has a MDA of 950 Bq and 1270 Bq for knee and skull, respectively, for a counting time of 1800 sec. This paper discusses the simulation method and the results obtained in the study.

Keywords: FLUKA Monte Carlo Method, ICRP adult male voxel phantom, knee, Skull.

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Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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Authors: I. Boroňová, J.Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, D. Gabriková, S. Mačeková

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Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.

Keywords: osteoporosis, real-time PCR method, SNP polymorphisms

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Authors: M. Nerantzaki, I. Koliakou, D. Bikiaris

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This study evaluates the hypothesis that the incorporation of fibrous hydroxyapatite nanoparticles (nHA) with high crystallinity and high aspect ratio, synthesized by hydrothermal method, into Poly(butylene succinate) (PBSu), improves the bioactivity of the aliphatic polyester and affects new bone growth inhibiting resorption and enhancing bone formation. Hydroxyapatite nanorods were synthesized using a simple hydrothermal procedure. First, the HPO42- -containing solution was added drop-wise into the Ca2+-containing solution, while the molar ratio of Ca/P was adjusted at 1.67. The HA precursor was then treated hydrothermally at 200°C for 72 h. The resulting powder was characterized using XRD, FT-IR, TEM, and EDXA. Afterwards, PBSu nanocomposites containing 2.5wt% (nHA) were prepared by in situ polymerization technique for the first time and were examined as potential scaffolds for bone engineering applications. For comparison purposes composites containing either 2.5wt% micro-Bioglass (mBG) or 2.5wt% mBG-nHA were prepared and studied, too. The composite scaffolds were characterized using SEM, FTIR, and XRD. Mechanical testing (Instron 3344) and Contact Angle measurements were also carried out. Enzymatic degradation was studied in an aqueous solution containing a mixture of R. Oryzae and P. Cepacia lipases at 37°C and pH=7.2. In vitro biomineralization test was performed by immersing all samples in simulated body fluid (SBF) for 21 days. Biocompatibility was assessed using rat Adipose Stem Cells (rASCs), genetically modified by nucleofection with DNA encoding SB100x transposase and pT2-Venus-neo transposon expression plasmids in order to attain fluorescence images. Cell proliferation and viability of cells on the scaffolds were evaluated using fluoresce microscopy and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay. Finally, osteogenic differentiation was assessed by staining rASCs with alizarine red using cetylpyridinium chloride (CPC) method. TEM image of the fibrous HAp nanoparticles, synthesized in the present study clearly showed the fibrous morphology of the synthesized powder. The addition of nHA decreased significantly the contact angle of the samples, indicating that the materials become more hydrophilic and hence they absorb more water and subsequently degrade more rapidly. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. Metabolic activity of rASCs on all PBSu composites was high and increased from day 1 of culture to day 14. On day 28 metabolic activity of rASCs cultured on samples enriched with bioceramics was significantly decreased due to possible differentiation of rASCs to osteoblasts. Staining rASCs with alizarin red after 28 days in culture confirmed our initial hypothesis as the presence of calcium was detected, suggesting osteogenic differentiation of rACS on PBSu/nHAp/mBG 2.5% and PBSu/mBG 2.5% composite scaffolds.

Keywords: biomaterials, hydroxyapatite nanorods, poly(butylene succinate), scaffolds

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Authors: Eni Rahmi, Rasmi Rikmasari, Taufik Soemarsongko

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Background: One of the bad habits that requires a treatment and viewed as a risk factor of the temporomandibular disorder is bruxism. Bruxism defined as an awake and/or asleep parafunctional activities include grinding, gnashing, bracing or clenching of the teeth. In particular circumstances such as an increased frequency of episode, duration and the intensity of masseter contractions, caused phenomenon with pathological consequences, i.e., mandibular remodeling. The remodeling in mandibular angle was associated with the masseter and pterygoid medial muscles attachment which in its insertion area. The aim of this study was to compare the mandibular remodeling between bruxers and non-bruxers with ramus height, gonial angle and bigonial width as parameters, and to identify correlation among those parameters in bruxers, using panoramic radiographic. Methods: This study was conducted on 35 bruxers (10 phasic bruxism patients, 6 tonic bruxism patients, and 19 mixed bruxism patients) and 20 non-bruxers as control group. The data were obtained by using questionary, clinical examination, and radiographic measurement. Panoramic radiograph measurement was done using soft CBCT EPX Impla (E-Woo Korea). The data was analyzed by using Paired T-Test to see differences between parameters in both group and Pearson Correlation Test to evaluate correlation among parameters. Result: There was significant differences between bruxers and non-bruxers in ramus heights (p=0,04), bigonial widths (p=0,001), and gonial angles(p=0,015). The bruxers showed increased ramus heights and bigonial widths, in other hand, the gonial angles decreased. This study also found that there was highly correlation among ramus height, gonial angles, and bigonial widths. Conclusion: the bone remodeling occurred on inferior and posterior border of mandibular angle in bruxism patient, indicated by the form and size differences between bruxers (phasic bruxism, tonic bruxism, and mixed bruxism) with non-bruxers, which shown by panoramic radiograph.

Keywords: bruxism, ramus height, gonial angle, bigonial width

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Authors: Kanchan Maji, Debasmita Pani, Sudip Dasgupta

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Calcium phosphate cement (CPC) due to its high bioactivity and optimum bioresorbability shows excellent bone regeneration capability. Despite it has limited applications as bone implant due to its macro-porous microstructure causing its poor mechanical strength. The reinforcement of apatitic CPCs with biocompatible fibre glass phase is an attractive area of research to improve its mechanical strength. Here we study the setting behaviour of Si-doped and un-doped alpha tri-calcium phosphate (α-TCP) based CPC and its reinforcement with the addition of E-glass fibre. Alpha tri-calcium phosphate powders were prepared by solid state sintering of CaCO3, CaHPO4 and tetra ethyl ortho silicate (TEOS) was used as silicon source to synthesise Si doped α-TCP powders. Alpha tri-calcium phosphate based CPC hydrolyzes to form hydroxyapatite (HA) crystals having excellent osteoconductivity and bone-replacement capability thus self-hardens through the entanglement of HA crystals. Setting time, phase composition, hydrolysis conversion rate, microstructure, and diametral tensile strength (DTS) of un-doped CPC and Si-doped CPC were studied and compared. Both initial and final setting time of the developed cement was delayed because of Si addition. Crystalline phases of HA (JCPDS 9-432), α-TCP (JCPDS 29-359) and β-TCP (JCPDS 9-169) were detected in the X-ray diffraction (XRD) pattern after immersion of CPC in simulated body fluid (SBF) for 0 hours to 10 days. The intensities of the α-TCP peaks of (201) and (161) at 2θ of 22.2°and 24.1° decreased when the time of immersion of CPC in SBF increased from 0 hours to 10 days, due to its transformation into HA. As Si incorporation in the crystal lattice stabilised the TCP phase, Si doped CPC showed a little slower rate of conversion into HA phase as compared to un-doped CPC. The SEM image of the microstructure of hardened CPC showed lower grain size of HA in un-doped CPC because of premature setting and faster hydrolysis of un-doped CPC in SBF as compared that in Si-doped CPC. Premature setting caused generation of micro and macro porosity in un-doped CPC structure which resulted in its lower mechanical strength as compared to that in Si-doped CPC. This lower porosity and greater compactness in the microstructure attributes to greater DTS values observed in Si-doped CPC. E-glass fibres of the average diameter of 12 μm were cut into approximately 1 mm in length and immersed in SBF to deposit carbonated apatite on its surface. This was performed to promote HA crystal growth and entanglement along the fibre surface to promote stronger interface between dispersed E-glass fibre and CPC matrix. It was found that addition of 10 wt% of E-glass fibre into Si-doped α-TCP increased the average DTS of CPC from 8 MPa to 15 MPa as the fibres could resist the propagation of crack by deflecting the crack tip. Our study shows that biocompatible E-glass fibre in optimum proportion in CPC matrix can enhance the mechanical strength of CPC without affecting its bioactivity.

Keywords: Calcium phosphate cement, biocompatibility, e-glass fibre, diametral tensile strength

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Authors: Staniek Halina

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The inappropriate trace elements supply such as iron(III) and chromium(III) may be risk factors of many metabolic disorders (e.g., anemia, diabetes, as well cause toxic effect). However, little is known about their mutual interactions and their impact on these disturbances. The effects of Cr(III) supplementation with a deficit or excess supply of Fe(III) in vivo conditions are not known yet. The objective of the study was to investigate the combined effect of different Fe(III) levels in the diet and simultaneous Cr(III) supplementation on the Ca distribution in organs in healthy rats. The assessment was based on a two-factor (2x3) experiment carried out on 54 female Wistar rats (Rattus norvegicus). The animals were randomly divided into 9 groups and for 6 weeks, they were fed semi-purified diets AIN-93 with three different Fe(III) levels in the diet as a factor A [control (C) 45 mg/kg (100% Recommended Daily Allowance for rodents), deficient (D) 5 mg/kg (10% RDA), and oversupply (H) 180 mg/kg (400% RDA)]. The second factor (B) was the simultaneous dietary supplementation with Cr(III) at doses of 1, 50 and 500 mg/kg of the diet. Iron(III) citrate was the source of Fe(III). The complex of Cr(III) with propionic acid, also called Cr₃ or chromium(III) propionate (CrProp), was used as a source of Cr(III) in the diet. The Ca content of analysed samples (liver, kidneys, spleen, heart, and femur) was determined with the Atomic Absorption Spectrometry (AAS) method. It was found that different dietary Fe(III) supply as well as Cr(III) supplementation independently and in combination influenced Ca metabolism in healthy rats. Regardless of the supplementation of Cr(III), the oversupply of Fe(III) (180 mg/kg) decreased the Ca content in the liver and kidneys, while it increased the Ca saturation of bone tissue. High Cr(III) doses lowered the hepatic Ca content. Moreover, it tended to decrease the Ca content in the kidneys and heart, but this effect was not statistically significant. The combined effect of the experimental factors on the Ca content in the liver and the femur was observed. With the increase in the Fe(III) content in the diet, there was a decrease in the Ca level in the liver and an increase in bone saturation, and the additional Cr(III) supplementation intensified those effects. The study proved that the different Fe(III) content in the diet, independently and in combination with Cr(III) supplementation, affected the Ca distribution in organisms of healthy rats.

Keywords: calcium, chromium(III), iron(III), rats, supplementation

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Authors: Amirhossein Moghanian, Morteza Elsa, Mehrnaz Aminitabar

Abstract:

Modified bioactive glass has been considered as a promising multifunctional candidate in bone repair and regeneration due to its attractive properties. The present study mainly aims to evaluate how the individual substitution of lithium (L-BG) and magnesium (M-BG) for calcium can affect the in vitro bioactivity of sol-gel derived substituted 58S bioactive glass (BG); and to present one composition in both of the 60SiO2–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂ –(36-x)CaO–4P₂O₅–(x)MgO quaternary systems (where x= 0, 5, 10 mol.%) with improved biocompatibility, enhanced alkaline phosphatase (ALP) activity, and the most efficient antibacterial activity against methicillin-resistant staphylococcus aureus bacteria. To address these aims, and study the effect of CaO/Li₂O and CaO/MgO substitution up to 10 mol % in 58S-BGs, the samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry and scanning electron microscopy after immersion in simulated body fluid up to 14 days. Results indicated that substitution of either CaO/ Li₂O and CaO/ MgO had a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium had a more pronounced effect. The 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and alkaline phosphatase (ALP) assays showed that both substitutions of CaO/ Li₂O and CaO/ MgO up to 5mol % in 58s-BGs led to increased biocompatibility and stimulated proliferation of the pre-osteoblast MC3T3 cells with respect to the control. On the other hand, the substitution of either Li or Mg for Ca in the 58s BG composition resulted in improved bactericidal efficiency against MRSA bacteria. Taken together, sample 58s-BG with 5 mol % CaO/Li₂O substitution (BG-5L) was considered as a multifunctional biomaterial in bone repair/regeneration with improved biocompatibility, enhanced ALP activity as well as significant antibacterial activity against methicillin-resistant staphylococcus aureus (MRSA) bacteria.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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