Search results for: bone carcinoma

Authors: Omar Nouri, Wafa Mnejja, Nejla Fourati, Fatma Dhouib, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Jamel Daoud

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Background and objective: Induction chemotherapy (IC) followed by concomitant chemo radiotherapy with intensity modulated radiation (IMRT) technique is actually the recommended treatment modality for locally advanced nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the prognostic factors predicting loco regional relapse with this new treatment protocol. Patients and methods: A retrospective study of 52 patients with NPC treated between June 2016 and July 2019. All patients received IC according to the protocol of the Head and Neck Radiotherapy Oncology Group (Gortec) NPC 2006 (3 TPF courses) followed by concomitant chemo radiotherapy with weekly cisplatin (40 mg / m2). Patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. Median age was 49 years (19-69) with a sex ratio of 3.3. Forty five tumors (86.5%) were classified as stages III - IV according to the 2017 UICC TNM classification. Loco regional relapse (LRR) was defined as a local and/or regional progression that occurs at least 6 months after the end of treatment. Survival analysis was performed according to Kaplan-Meier method and Log-rank test was used to compare anatomy clinical and therapeutic factors that may influence loco regional free survival (LRFS). Results: After a median follow up of 42 months, 6 patients (11.5%) experienced LRR. A metastatic relapse was also noted for 3 of these patients (50%). Target volumes coverage was optimal for all patient with LRR. Four relapses (66.6%) were in high-risk target volume and two (33.3%) were borderline. Three years LRFS was 85,9%. Four factors predicted loco regional relapses: histologic type other than undifferentiated (UCNT) (p=0.027), a macroscopic pre chemotherapy tumor volume exceeding 100 cm³ (p=0.005), a reduction in IC doses exceeding 20% (p=0.016) and a total cumulative cisplatin dose less than 380 mg/m² (p=0.0.34). TNM classification and response to IC did not impact loco regional relapses. Conclusion: For nasopharyngeal carcinoma, tumors with initial high volume and/or histologic type other than UCNT, have a higher risk of loco regional relapse. Therefore, they require a more aggressive therapeutic approaches and a suitable monitoring protocol.

Keywords: loco regional relapse, modulation intensity radiotherapy, nasopharyngeal carcinoma, prognostic factors

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Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

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Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

Procedia PDF Downloads 219

Authors: Kazeem Adesina Dauda, Waheed Babatunde Yahya

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To design a tree that maximizes within-node homogeneity, there is a need for a homogeneity measure that is appropriate for event history data with multiple risks. We consider the use of Deviance and Modified Cox-Snell residuals as a measure of impurity in Classification Regression Tree (CART) and compare our results with the results of Fiona (2008) in which homogeneity measures were based on Martingale Residual. Data structure approach was used to validate the performance of our proposed techniques via simulation and real life data. The results of univariate competing risk revealed that: using Deviance and Cox-Snell residuals as a response in within node homogeneity classification tree perform better than using other residuals irrespective of performance techniques. Bone marrow transplant data and double-blinded randomized clinical trial, conducted in other to compare two treatments for patients with prostate cancer were used to demonstrate the efficiency of our proposed method vis-à-vis the existing ones. Results from empirical studies of the bone marrow transplant data showed that the proposed model with Cox-Snell residual (Deviance=16.6498) performs better than both the Martingale residual (deviance=160.3592) and Deviance residual (Deviance=556.8822) in both event of interest and competing risks. Additionally, results from prostate cancer also reveal the performance of proposed model over the existing one in both causes, interestingly, Cox-Snell residual (MSE=0.01783563) outfit both the Martingale residual (MSE=0.1853148) and Deviance residual (MSE=0.8043366). Moreover, these results validate those obtained from the Monte-Carlo studies.

Keywords: within-node homogeneity, Martingale residual, modified Cox-Snell residual, classification and regression tree

Procedia PDF Downloads 258

Authors: Robnier Reyes, Andrew J. P. Marques, Joel Ramjist, Chris R. Pasarikovski, Victor X. D. Yang

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Over the past three decades, surgical robotic systems have demonstrated their ability to improve surgical outcomes. The LBR Med is a collaborative robotic arm that is meant to work with a surgeon to streamline surgical workflow. It has 7 degrees of freedom and thus can be easily oriented. Position and torque sensors at each joint allow it to maintain a position accuracy of 150 µm with real-time force and torque feedback, making it ideal for complex surgical procedures. Spinal fusion procedures involve the placement of as many as 20 pedicle screws, requiring a great deal of accuracy due to proximity to the spinal canal and surrounding vessels. Any deviation from intended path can lead to major surgical complications. Assistive surgical robotic systems are meant to serve as collaborative devices easing the workload of the surgeon, thereby improving pedicle screw placement by mitigating fatigue related inaccuracies. Moreover, robotic spinal systems have shown marked improvements over conventional freehanded techniques in both screw placement accuracy and fusion quality and have greatly reduced the need for screw revision, intraoperatively and post-operatively. However, current assistive spinal fusion robots, such as the ROSA Spine, are limited in functionality to positioning surgical instruments. While they offer a small degree of improvement in pedicle screw placement accuracy, they do not alleviate surgeon fatigue, nor do they provide real-time force and torque feedback during screw insertion. We propose a semi-autonomous surgical robot workflow for spinal fusion where the surgeon guides the robot to its initial position and orientation, and the robot drives the pedicle screw accurately into the vertebra. Here, we demonstrate feasibility by inserting pedicle screws into ex-vivo bovine rib bone. The robot monitors position, force and torque with respect to predefined values selected by the surgeon to ensure the highest possible spinal fusion quality. The workflow alleviates the strain on the surgeon by having the robot perform the screw placement while the ability to monitor the process in real-time keeps the surgeon in the system loop. The approach we have taken in terms of level autonomy for the robot reflects its ability to safely collaborate with the surgeon in the operating room without external navigation systems.

Keywords: ex vivo bovine bone, pedicle screw, surgical robot, surgical workflow

Procedia PDF Downloads 159

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: O. O. Onafowokan, K. Anderson, M. R. Norton, R. G. Middleton

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Revision total hip arthroplasty (THA) is known to be a challenging procedure with potential for poor outcomes. Due to its lack of metaphyseal encroachment, hip resurfacing arthroplasty (HRA) is classified as a bone conserving procedure. Although the literature postulates that this is an advantage at time of revision surgery, there is no evidence to either support or refute this claim. We identified 129 hips that had undergone HRA and 129 controls undergoing first revision THA. We recorded the clinical assessment and survivorship of implants in a multi-surgeon, single centre, retrospective case control series for both arms. These were matched for age and sex. Data collected included demographics, indications for surgery, Oxford Hip Score (OHS), length of surgery, length of hospital stay, blood transfusion, implant complexity and further surgical procedures. Significance was taken as p < 0.05. Mean follow up was 7.5 years (1 to 15). There was a significant 6 point difference in postoperative OHS in favour of the revision resurfacing group (p=0.0001). The revision HRA group recorded 48 minutes less length of surgery (p<0.0001), 2 days less in length of hospital stay (p=0.018), a reduced need for blood transfusion (p=0.0001), a need for less complexity in revision implants (p=0.001) and a reduced probability of further surgery being required (P=0.003). Whilst we acknowledge the limitations of this study our results suggest that, in contrast to THA, the bone conservation element of HRA may make for a less traumatic revision procedure with better functional outcomes. Use of HRA has seen a dramatic decline as a result of concerns regarding metallosis. However, this information remains of relevance when counselling young active patients about their arthroplasty options and may become pertinent in the future if the promise of ceramic hip resurfacing is ever realized.

Keywords: hip resurfacing, metallosis, revision surgery, total hip arthroplasty

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Authors: Chih-Hsien Chen, Yi-Hung Ho, Chih-Wei Wang, Chih-Wei Chang, Yen-Nien Chen, Chih-Han Chang, Chun-Ting Li

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Laminotomy is a spinal decompression surgery compatible with a minimally invasive approach. However, the unilateral laminotomy for bilateral side decompression leads to more perioperative complications than the bilateral laminotomy. Although the unilateral laminotomy removes the least bone tissue among the spinal decompression surgeries, the difference of spinal stability between unilateral and bilateral laminotomy and laminectomy is rarely investigated. This study aims to compare the biomechanical effects of unilateral and bilateral laminotomy and laminectomy on the lumbar spine by finite element (FE) simulation. A three-dimensional FE model of the lumbar spine (L1–L5) was constructed with the vertebral body, discs, and ligaments, as well as the sacrum was constructed. Three different surgical methods, namely unilateral laminotomy, bilateral laminotomy and laminectomy, at L3–L4 and L4–L5 were considered. Partial pedicle and entire ligamentum flavum were removed to simulate bilateral decompression in laminotomy. The entire lamina and spinal processes from the lower L3 to upper L5 were detached in the laminectomy model. Then, four kinds of loadings, namely flexion, extension, lateral bending and rotation, were applied on the lumbar with various decompression conditions. The results indicated that the bilateral and unilateral laminotomy both increased the range of motion (ROM) compared with intact lumbar, while the laminectomy increased more ROM than both laminotomy did. The difference of ROM between the bilateral and unilateral laminotomy was very minor. Furthermore, bilateral laminotomy demonstrated similar poster element stress with unilateral laminotomy. Unilateral and bilateral laminotomy are equally suggested to bilateral decompression of lumbar spine with minimally invasive technique because limited effect was aroused due to more bone remove in the bilateral laminotomy on the lumbar stability. Furthermore, laminectomy is the last option for lumbar decompression.

Keywords: minimally invasive technique, lumbar decompression, laminotomy, laminectomy, finite element method

Procedia PDF Downloads 173

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Cristina Busuioc, Georgeta Voicu, Sorin-Ion Jinga

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The human bone presents in its dry form piezoelectric properties, which means that a mechanical stress results in electric polarization and an applied electric field causes strain. The immediate consequence was the revealing of piezoelectricity role in bone remodelling, as well as the integration of ceramic materials with piezoelectric behaviour in the composition of unitary or composite biomaterials. Thus, we prepared hydroxyapatite - collagen hybrid materials with barium titanate addition in order to achieve a better osseointegration. Barium titanate powder synthesized by a combined sol-gel-hydrothermal method, commercial hydroxyapatite and laboratory extracted collagen gel were employed as starting materials. Before the composites, fabrication, the powder with piezoelectric features was characterized in detail from the compositional, structural, morphological and electrical point of view. The next step was to elucidate the influence of barium titanate presence especially on the biological properties of the final materials. The biocompatibility of the hybrid supports without or with piezoelectric addition was investigated on mouse osteoblast cells through LDH cytotoxicity assay, LIVE/DEAD cell viability assay, and MTT cell proliferation assay. All results indicated that the analysed materials do not exert cytotoxic effects and present the ability to sustain cell survival and to promote their proliferation. In conclusion, barium titanate nanoparticles exhibit a good biocompatibility and osteoinductive properties, while the derived composite materials based on hydroxyapatite as oxide phase and collagen as polymeric phase can be successfully used for tissue engineering applications.

Keywords: barium titanate, hybrid composites, piezoelectricity, tissue engineering

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Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

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Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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Authors: Ananya Hazare, Ranjit Kamble

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Introduction: Patients with Cleft lip and palate (CL/P) can present with a maxillary retrution after cleft repair. Anterior Maxillary distraction osteogenesis (AMD) is a technique that provides simultaneous skeletal advancement and expansion of the soft tissues related to an anterior segment of the maxilla. This case presented is a case of AMD. The advantage of this technique is that the occlusion in the posterior segment can be maintained, and only the segment in cross bite is advanced for correction of the midfacial deficiency. The other alternative treatment is anterior movement by a Lefort 1 osteotomy. When a Lefort 1 osteotomy is compared with the Distraction osteogenesis or AMD, the disadvantages of the Le Fort 1 include a higher risk of morbidity, requirement of fixation, relapse tendency and unexpected changes in the nasal form. These complications were eliminated by AMD technique. This was followed by placement of the implant in the bone formed after AMD. Hence complete surgical, orthodontic and prosthodontics rehabilitation of the patient was done by an interdisciplinary approach. Methods: Patient presented with repaired UCL/P of the right side with midfacial retrusion. Intro-oral examination revealed a good occlusion in the posterior arch and anterior Crossbite from canine to canine. Patient's both maxillary lateral incisors were missing. The lower arch was well aligned with all teeth present. The study models when scored according to GOSLON yardstick received a score of 4. After pre-surgical orthodontic phase was completed an intraoral distractor was fabricated by modification of HYRAX expansion screw. After surgery, low subapical osteotomy cuts were placed and the distractor was fixed. The latency period of 5 days was observed after which the distraction was started. Distraction was done at a rate of 1 mm/day with a rhythm of 0.5mm in morning and 0.5mm in the evening. The total distraction of 12 mm was done. After a consolidation period, the distractor was removed, and retention by a removable partial denture was given. Radiographic examination confirmed mature bone formation in the distracted segment. Implants were placed and allowed to osseointegrate for approximately 4 months and were then loaded with abutments. Results: Total distraction done was 12mm and after relapse it was 8mm. After consolidation phase the radiographic examination revealed a B2 quality of bone according to the Misch's classification and sufficient height from the maxillary sinus. These findings were indicative for placement of implants in the distracted bone formed in premolar region. Implants were placed and after radiographic evidence of osseointegration was seen they were loaded with abutments. Thus resulting in a complete rehabilitation of a cleft patient by an interdisciplinary approach. Conclusion: Anterior maxillary distraction can be used as an alternative method instead of complete distraction osteogenesis or Lefort 1 advancement of maxilla in cases where the advancement needed is minimum. Use of HYRAX expansion screw modified as intra-oral distractor can be used in such cases, which significantly reduces the cost of treatment, as expensive distractors are not used. This technique is very useful and efficient in countries like India where the patient cannot afford expensive treatment options.

Keywords: cleft lip and palate, distraction osteogenesis, anterior maxillary distraction, orthodontics and dentofacial orthopaedics, hyrax expansion screw modification

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Authors: Azadeh Rouhandeh, Chris Joslin, Zhen Qu, Yuu Ono

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The centre of rotation of the hip joint is needed for an accurate simulation of the joint performance in many applications such as pre-operative planning simulation, human gait analysis, and hip joint disorders. In human movement analysis, the hip joint center can be estimated using a functional method based on the relative motion of the femur to pelvis measured using reflective markers attached to the skin surface. The principal source of errors in estimation of hip joint centre location using functional methods is soft tissue artefacts due to the relative motion between the markers and bone. One of the main objectives in human movement analysis is the assessment of soft tissue artefact as the accuracy of functional methods depends upon it. Various studies have described the movement of soft tissue artefact invasively, such as intra-cortical pins, external fixators, percutaneous skeletal trackers, and Roentgen photogrammetry. The goal of this study is to present a non-invasive method to assess the displacements of the markers relative to the underlying bone using optical motion capture data and tissue thickness from ultrasound measurements during flexion, extension, and abduction (all with knee extended) of the hip joint. Results show that the artefact skin marker displacements are non-linear and larger in areas closer to the hip joint. Also marker displacements are dependent on the movement type and relatively larger in abduction movement. The quantification of soft tissue artefacts can be used as a basis for a correction procedure for hip joint kinematics.

Keywords: hip joint center, motion capture, soft tissue artefact, ultrasound depth measurement

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Authors: Naghmeh Zamani, Ashkan Pourkand, David Grow

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This paper presents the design and mechanical model of a hybrid impedance/admittance haptic device optimized for applications, like bone drilling, spinal awl probe use, and other surgical techniques were high force is required in the tool-axial direction, and low impedance is needed in all other directions. The performance levels required cannot be satisfied by existing, off-the-shelf haptic devices. This design may allow critical improvements in simulator fidelity for surgery training. The device consists primarily of two low-mass (carbon fiber) plates with a rod passing through them. Collectively, the device provides 6 DOF. The rod slides through a bushing in the top plate and it is connected to the bottom plate with a universal joint, constrained to move in only 2 DOF, allowing axial torque display the user’s hand. The two parallel plates are actuated and located by means of four cables pulled by motors. The forward kinematic equations are derived to ensure that the plates orientation remains constant. The corresponding equations are solved using the Newton-Raphson method. The static force/torque equations are also presented. Finally, we present the predicted distribution of location error, cables velocity, cable tension, force and torque for the device. These results and preliminary hardware fabrication indicate that this design may provide a revolutionary approach for haptic display of many surgical procedures by means of an architecture that allows arbitrary workspace scaling. Scaling of the height and width can be scaled arbitrarily.

Keywords: cable direct driven robot, haptics, parallel plates, bone drilling

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Tannaz Alimardani, Amirhossein Moghanian, Morteza Elsa

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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with a nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of the opposite effect of Sr and Li of the dissolution of BG in the SBF, but also stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on the dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with the live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S bioactive glass exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: alkaline, alkaline earth, bioglass, co-doping, ion release

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Authors: Ananya Ananya, Karthik Rao

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Accurate segmentation of knee cartilage in 3-D magnetic resonance (MR) images for quantitative assessment of volume is crucial for studying and diagnosing osteoarthritis (OA) of the knee, one of the major causes of disability in elderly people. Radiologists generally perform this task in slice-by-slice manner taking 15-20 minutes per 3D image, and lead to high inter and intra observer variability. Hence automatic methods for knee cartilage segmentation are desirable and are an active field of research. This paper presents design and experimental evaluation of 2D convolutional neural networks based fully automated methods for knee cartilage segmentation in 3D MRI. The architectures are validated based on 40 test images and 60 training images from SKI10 dataset. The proposed methods segment 2D slices one by one, which are then combined to give segmentation for whole 3D images. Proposed methods are modified versions of U-net and dilated convolutions, consisting of a single step that segments the given image to 5 labels: background, femoral cartilage, tibia cartilage, femoral bone and tibia bone; cartilages being the primary components of interest. U-net consists of a contracting path and an expanding path, to capture context and localization respectively. Dilated convolutions lead to an exponential expansion of receptive field with only a linear increase in a number of parameters. A combination of modified U-net and dilated convolutions has also been explored. These architectures segment one 3D image in 8 – 10 seconds giving average volumetric Dice Score Coefficients (DSC) of 0.950 - 0.962 for femoral cartilage and 0.951 - 0.966 for tibia cartilage, reference being the manual segmentation.

Keywords: convolutional neural networks, dilated convolutions, 3 dimensional, fully automated, knee cartilage, MRI, segmentation, U-net

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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: 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: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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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: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

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Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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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: Uma Krishnamoorthy, Vivienne Beavers, Janet Marshall

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Introduction: Cervical cytology showing features raising the suspicion of non cervical glandular neoplasia are reported as code 0 under the United Kingdom National Health Service Cervical screening programme ( NHSCSP). As the suspicion is regarding non cervical neoplasia, smear is reported as normal and patient informed that cervical screening result is normal. GP receives copy of results where it states further referral is indicated in small font within text of report. Background: There were several incidents of delayed diagnosis of endometrial cancer in Lancashire which prompted this Northwest Regional review to enable an understanding of underlying pathology outcome of code zero smears to raise awareness and also to review whether further action on wording of smear results was indicated to prevent such delay. Methodology: All Smears reported at the Manchester cytology centre who process cytology for Lancashire population from March 2013 to March 2014 were reviewed and histological diagnosis outcome of women in whom smear was reported as code zero was reviewed retrospectively . Results: Total smears reported by the cytology centre during this period was approximately 109400. Reports issued with result code 0 among this during this time period was 49.Results revealed that among three fourth (37) of women with code zero smear (N=49), evidence of underlying pathology of non cervical origin was confirmed. Of this, 73 % (36) were due to endometrial pathology with 49 % (24) endometrial carcinoma, 12 % (6)polyp, 4 % atypical endometrial hyperplasia (2), 6 % endometrial hyperplasia without atypia (3), and 2 % adenomyosis (1 case) and 2 % ( 1 case) due to ovarian adenocarcinoma. Conclusion: This review demonstrated that more than half (51 %) of women with a code 0 smear report were diagnosed with underlying carcinoma and 75 % had a confirmed underlying pathology contributory to code 0 smear findings. Recommendations and Action Plan: A local rapid access referral and management pathway for this group of women was implemented as a result of this in our unit. The findings and Pathway were shared with other regional units served by the cytology centre through the Pan Lancashire cervical screening board and through the Cytology centre. Locally, the smear report wording was updated to include a rubber stamp/ print in "Red Bold letters" stating that " URGENT REFERRAL TO GYNAECOLOGY IS INDICATED". Findings were also shared through the Pan Lancashire board with National cervical screening programme board, and revisions to wording of code zero smear reports to highlight the need for Urgent referral has now been agreed at National level to be implemented.

Keywords: code zero smears, endometrial cancer, non cervical glandular neoplasia, ovarian cancer

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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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