Search results for: umbilical cord milking
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 205

Search results for: umbilical cord milking

25 Pentosan Polysulfate Sodium: A Potential Treatment to Improve Bone and Joint Manifestations of Mucopolysaccharidosis I

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

Abstract:

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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24 Maternal Perception of Using Epidural Anesthesia and the Childbirth Outcomes

Authors: Jiyoung Kim, Chae Weon Chung

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Labor pain is one of the most common concerns of pregnant women, thus women are in need of possible options they could take to control the pain. So, this study aimed to explore maternal perception of epidural anesthesia and to compare the childbirth outcomes according to the use of epidural anesthesia. For this descriptive study, women who were over 36 weeks of pregnancy were recruited from an out-patient obstetric clinic in a public hospital in Seoul. Women were included in the study if agreed to participate, were pregnant singleton, without pregnancy complication, and expecting a natural birth. Data collection was done twice, the first one at the prenatal care visit and the second one at an in-patient ward on 2nd day postpartum. The instrument of the beliefs about epidural anesthesia, one item of asking intention to use epidural anesthesia, demographics, and obstetrical characteristics were incorporated into a questionnaire. One nurse researcher performed data collection with the structured questionnaire after the approval of the institutional review board. At the initial data collection 133 women were included, while 117 were retained at the second point after excluded 13 women due to the occurrence of complications. Analyses were done by chi-square, t-test, and ANOVA using the SPSS program. Women were aged 32.5 years old, 22.2% were over 35 years old. The average gestational age was 38.5 weeks, and 67.5% were nulliparous. Out of 38 multiparous women, 20 women (52.6%) had received epidural anesthesia in the previous delivery. At the initial interview, 62.6% (n=73) of women wanted to receive epidural anesthesia while 22.4% answered not decided and 15.4% did not want to take the procedure. However, there were changes in proportions between women’s intention to take it and actual procedures done, particularly, two-thirds of women (n=26) who had been undecided were found to receive epidural anesthesia during labor. There was a significant difference in the perception of epidural anesthesia measured before delivery between women who received and not received it (t=3.68, p < .001). Delivery outcomes were statistically different between the two groups in delivery mode (chi-square=8.64, p=.01), O₂ supply during labor (chi-square =5.01, p=.03), duration of 2nd stage of labor (t=3.70, p < .001), and arterial cord blood pH (t=2.64, p=.01). Interestingly, there was no difference in labor pain perceived between women with and without epidural anesthesia. Considering the preference and use of epidural anesthesia, health professionals need to assess coping ability of women undergoing delivery and to provide accurate information about pain control to support their decision making and eventually to enhance delivery outcomes for mothers and neonates.

Keywords: epidural anesthesia, delivery outcomes, labor pain, perception

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23 Regulation of the Regeneration of Epidermal Langerhans Cells by Stress Hormone

Authors: Junichi Hosoi

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Epidermal Langerhans cells reside in upper layer of epidermis and play a role in immune surveillance. The finding of the close association of nerve endings to Langerhans cells triggered the research on systemic regulation of Langerhans cells. They disappear from epidermis after exposure to environmental and internal stimuli and reappear about a week later. Myeloid progenitor cells are assumed to be one of the sources of Langerhans cells. We examined the effects of cortisol on the reappearance of Langerhans cells in vitro. Cord-blood derived CD34-positive cells were cultured in the medium supplemented with stem cell factor/Flt3 ligand/granulocyte macrophage-colony stimulating factor/tumor necrosis factor alpha/bone morphologic protein 7/transforming growth factor beta in the presence or absence of cortisol. Cells were analyzed by flow cytometry for CD1a (cluster differentiation 1a), a marker of Langerhans cells and dermal dendritic cells, and CD39 (cluster differentiation factor 39), extracellular adenosine triphosphatase. Both CD1a-positive cells and CD39-positive cells were decreased by treatment with cortisol (suppression by 35% and 22% compared to no stress hormone, respectively). Differentiated Langerhans cells are attracted to epidermis by chemokines that are secreted from keratinocytes. Epidermal keratinocytes were cultured in the presence or absence of cortisol and analyzed for the expression of CCL2 (C-C motif chemokine ligand 2) and CCL20 (C-C motif chemokine ligand 20), which are typical attractants of Langerhans cells, by quantitative reverse transcriptase polymerase chain reaction. The expression of both chemokines, CCL2 and CCL20, were suppressed by treatment with cortisol (suppression by 38% and 48% compared to no stress hormone, respectively). We examined the possible regulation of the suppression by cortisol with plant extracts. The extracts of Ganoderma lucidum and Iris protected the suppression of the differentiation to CD39-positive cells and also the suppression of the gene expression of LC-chemoattractants. These results suggest that cortisol, which is either systemic or locally produced, blocks the supply of epidermal Langerhans cells at 2 steps, differentiation from the precursor and attraction to epidermis. The suppression is possibly blocked by some plant extracts.

Keywords: Langerhans cell, stress, CD39, chemokine

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22 Effects of Mental Skill Training Programme on Direct Free Kick of Grassroot Footballers in Lagos, Nigeria

Authors: Mayowa Adeyeye, Kehinde Adeyemo

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The direct free kick is considered a great opportunity to score a goal but this is not always the case amidst Nigerian and other elite footballers. This study, therefore, examined the extent to which an 8 weeks mental skill training programme is effective for improving accuracy in direct free kick in football. Sixty (n-60) students of Pepsi Football Academy participated in the study. They were randomly distributed into two groups of positive self-talk group (intervention n-30) and control group (n-30). The instrument used in the collection of data include a standard football goal post while the research materials include a dummy soccer wall, a cord, an improvised vanishing spray, a clipboard, writing materials, a recording sheet, a self-talk log book, six standard 5 football, cones, an audiotape and a compact disc. The Weinberge and Gould (2011) mental skills training manual was used. The reliability coefficient of the apparatus following a pilot study stood at 0.72. Before the commencement of the mental skills training programme, the participants were asked to take six simulated direct free kick. At the end of each physical skills training session after the pre-test, the researcher spent at least 15 minutes with the groups exposing them to the intervention. The mental skills training programme alongside physical skills training took place in two different locations for the different groups under study, these included Agege Stadium Main bowl Football Pitch (Imagery Group), and Ogba Ijaye (Control Group). The mental skills training programme lasted for eight weeks. After the completion of the mental skills training programme, all the participants were asked to take another six simulated direct free kick attempts using the same field used for the pre-test to determine the efficacy of the treatments. The pre-test and post-test data were analysed using inferential statistics of t-test, while the alpha level was set at 0.05. The result revealed significant differences in t-test for positive self-talk and control group. Based on the findings, it is recommended that athletes should be exposed to positive self-talk alongside their normal physical skills training for quality delivery of accurate direct free kick during training and competition.

Keywords: accuracy, direct free kick, pepsi football academy, positive self-talk

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21 A Versatile Standing Cum Sitting Device for Rehabilitation and Standing Aid for Paraplegic Patients

Authors: Sasibhushan Yengala, Nelson Muthu, Subramani Kanagaraj

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The abstract reports on the design related to a modular and affordable standing cum sitting device to meet the requirements of paraplegic patients of the different physiques. Paraplegic patients need the assistance of an external arrangement to the lower limbs and trunk to help patients adopt the correct posture while standing abreast gravity. This support can be from a tilt table or a standing frame which the patient can use to stay in a vertical posture. Standing frames are devices fitting to support a person in a weight-bearing posture. Commonly, these devices support and lift the end-user in shifting from a sitting position to a standing position. The merits of standing for a paraplegic patient with a spinal injury are numerous. Even when there is limited control on muscles that ordinarily support the user using the standing frame in a vertical position, the standing stance improves the blood pressure, increases bone density, improves resilience and scope of motion, and improves the user's feelings of well-being by letting the patient stand. One limitation with standing frames is that these devices are typically function definitely; cannot be used for different purposes. Therefore, users are often compelled to purchase more than one of these devices, each being purposefully built for definite activities. Another concern frequent in standing frames is manoeuvrability; it is crucial to provide a convenient adjustment scope for all users. Thus, there is a need to provide a standing frame with multiple uses that can be economical for a larger population. There is also a need to equip added readjustment means in a standing frame to lessen the shear and to accommodate a broad range of users. The proposed Versatile Standing cum Sitting Device (VSD) is designed to change from standing to a comfortable sitting position using a series of mechanisms. First, a locking mechanism is provided to lock the VSD in a standing stance. Second, a dampening mechanism is provided to make sure that the VSD shifts from a standing to a sitting position gradually when the lock mechanism gets disengaged. An adjustment option is offered for the height of the headrest via the use of lock knobs. This device can be used in clinics for rehabilitation purposes irrespective of patient's anthropometric data due to its modular adjustments. It can facilitate the patient's daily life routine while in therapy and giving the patient the comfort to sit when tired. The device also provides the availability of rehabilitation to a common person.

Keywords: paraplegic, rehabilitation, spinal cord injury, standing frame

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20 A Textile-Based Scaffold for Skin Replacements

Authors: Tim Bolle, Franziska Kreimendahl, Thomas Gries, Stefan Jockenhoevel

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The therapeutic treatment of extensive, deep wounds is limited. Autologous split-skin grafts are used as a so-called ‘gold standard’. Most common deficits are the defects at the donor site, the risk of scarring as well as the limited availability and quality of the autologous grafts. The aim of this project is a tissue engineered dermal-epidermal skin replacement to overcome the limitations of the gold standard. A key requirement for the development of such a three-dimensional implant is the formation of a functional capillary-like network inside the implant to ensure a sufficient nutrient and gas supply. Tailored three-dimensional warp knitted spacer fabrics are used to reinforce the mechanically week fibrin gel-based scaffold and further to create a directed in vitro pre-vascularization along the parallel-oriented pile yarns within a co-culture. In this study various three-dimensional warp knitted spacer fabrics were developed in a factorial design to analyze the influence of the machine parameters such as the stitch density and the pattern of the fabric on the scaffold performance and further to determine suitable parameters for a successful fibrin gel-incorporation and a physiological performance of the scaffold. The fabrics were manufactured on a Karl Mayer double-bar raschel machine DR 16 EEC/EAC. A fine machine gauge of E30 was used to ensure a high pile yarn density for sufficient nutrient, gas and waste exchange. In order to ensure a high mechanical stability of the graft, the fabrics were made of biocompatible PVDF yarns. Key parameters such as the pore size, porosity and stress/strain behavior were investigated under standardized, controlled climate conditions. The influence of the input parameters on the mechanical and morphological properties as well as the ability of fibrin gel incorporation into the spacer fabric was analyzed. Subsequently, the pile yarns of the spacer fabrics were colonized with Human Umbilical Vein Endothelial Cells (HUVEC) to analyze the ability of the fabric to further function as a guiding structure for a directed vascularization. The cells were stained with DAPI and investigated using fluorescence microscopy. The analysis revealed that the stitch density and the binding pattern have a strong influence on both the mechanical and morphological properties of the fabric. As expected, the incorporation of the fibrin gel was significantly improved with higher pore sizes and porosities, whereas the mechanical strength decreases. Furthermore, the colonization trials revealed a high cell distribution and density on the pile yarns of the spacer fabrics. For a tailored reinforcing structure, the minimum porosity and pore size needs to be evaluated which still ensures a complete incorporation of the reinforcing structure into the fibrin gel matrix. That will enable a mechanically stable dermal graft with a dense vascular network for a sufficient nutrient and oxygen supply of the cells. The results are promising for subsequent research in the field of reinforcing mechanically weak biological scaffolds and develop functional three-dimensional scaffolds with an oriented pre-vascularization.

Keywords: fibrin-gel, skin replacement, spacer fabric, pre-vascularization

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19 Neuromyelitis Optica area Postrema Syndrome(NMOSD-APS) in a Fifteen-year-old Girl: A Case Report

Authors: Merilin Ivanova Ivanova, Kalin Dimitrov Atanasov, Stefan Petrov Enchev

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Backgroud: Neuromyelitis optica spectrum disorder, also known as Devic’s disease, is a relapsing demyelinating autoimmune inflammatory disorder of the central nervous system associated with anti-aquaporin 4 (AQP4) antibodies that can manifest with devastating secondary neurological deficits. Most commonly affected are the optic nerves and the spinal cord-clinically this is often presented with optic neuritis (loss of vision), transverse myelitis(weakness or paralysis of extremities),lack of bladder and bowel control, numbness. APS is a core clinical entity of NMOSD and adds to the clinical representation the following symptoms: intractable nausea, vomiting and hiccup, it usually occurs isolated at onset, and can lead to a significant delay in the diagnosis. The condition may have features similar to multiple sclerosis (MS) but the episodes are worse in NMO and it is treated differently. It could be relapsing or monophasic. Possible complications are visual field defects and motor impairment, with potential blindness and irreversible motor deficits. In severe cases, myogenic respiratory failure ensues. The incidence of reported cases is approximately 0.3–4.4 per 100,000. Paediatric cases of NMOSD are rare but have been reported occasionally, comprising less than 5% of the reported cases. Objective: The case serves to show the difficulty when it comes to the diagnostic processes regarding a rare autoimmune disease with non- specific symptoms, taking large interval of rimes to reveal as complete clinical manifestation of the aforementioned syndrome, as well as the necessity of multidisciplinary approach in the setting of а general paediatric department in аn emergency hospital. Methods: itpatient's history, clinical presentation, and information from the used diagnostic tools(MRI with contrast of the central nervous system) lead us to the conclusion .This was later on confirmed by the positive results from the anti-aquaporin 4 (AQP4) antibody serology test. Conclusion: APS is a common symptom of NMOSD and is considered a challenge in a differential-diagnostic plan. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing thorough physical examinations are essential if we are to reduce and avoid misdiagnosis.

Keywords: neuromyelitis, devic's disease, hiccup, autoimmune, MRI

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18 Evaluation on the Compliance of Essential Intrapartum Newborn Care among Nurses in Selected Government Hospital in Manila

Authors: Eliza Torrigue, Efrelyn Iellamo

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Maternal death is one of the rising health issues in the Philippines. It is alarming to know that in every hour of each day, a mother gives birth to a child who may not live to see the next day. Statistics shows that intrapartum period and third stage of labor are the very crucial periods for the expectant mother, as well as the first six hours of life for the newborn. To address the issue, The Essential Intrapartum Newborn Care (EINC) was developed. Through this, Obstetric Delivery Room (OB-DR) Nurses shall be updated with the evidence-based maternal and newborn care to ensure patient safety, thus, reducing maternal and child mortality. This study aims to describe the compliance of hospitals, especially of OB-DR nurses, to the EINC Protocols. The researcher aims to link the profile variables of the respondents in terms of age, length of service and formal training to their compliance on the EINC Protocols. The outcome of the study is geared towards the development of appropriate training program for OB-DR Nurses assigned in the delivery room of the hospitals based on the study’s results to sustain the EINC standards. A descriptive correlational method was used. The sample consists of 75 Obstetric Delivery Room (OB-DR) Nurses from three government hospitals in the City of Manila namely, Ospital ng Maynila Medical Center, Tondo Medical Center, and Gat Andres Bonifacio Memorial Medical Center. Data were collected using an evaluative checklist. Ranking, weighted mean, Chi-square and Pearson’s R were used to analyze data. The level of compliance to the EINC Protocols by the respondents was evaluated with an overall mean score of 4.768 implying that OB-DR Nurses have a high regard in complying with the step by step procedure of the EINC. Furthermore, data shows that formal training on EINC have a significant relationship with OB-DR Nurses’ level of compliance during cord care, AMTSL, and immediate newborn care until the first ninety minutes to six hours of life. However, the respondents’ age and length of service do not have a significant relationship with the compliance of OB-DR Nurses on EINC Protocols. In the pursuit of decreasing the maternal mortality in the Philippines, EINC Protocols have been widely implemented in the country especially in the government hospitals where most of the deliveries happen. In this study, it was found out that OB-DR Nurses adhere and are highly compliant to the standards in order to assure that optimum level of care is delivered to the mother and newborn. Formal training on EINC, on the other hand, create the most impact on the compliance of nurses. It is therefore recommended that there must be a structured enhancement training program to plan, implement and evaluate the EINC protocols in these government hospitals.

Keywords: compliance, intrapartum, newborn care, nurses

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17 A Review of Brain Implant Device: Current Developments and Applications

Authors: Ardiansyah I. Ryan, Ashsholih K. R., Fathurrohman G. R., Kurniadi M. R., Huda P. A

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The burden of brain-related disease is very high. There are a lot of brain-related diseases with limited treatment result and thus raise the burden more. The Parkinson Disease (PD), Mental Health Problem, or Paralysis of extremities treatments had risen concern, as the patients for those diseases usually had a low quality of life and low chance to recover fully. There are also many other brain or related neural diseases with the similar condition, mainly the treatments for those conditions are still limited as our understanding of the brain function is insufficient. Brain Implant Technology had given hope to help in treating this condition. In this paper, we examine the current update of the brain implant technology. Neurotechnology is growing very rapidly worldwide. The United States Food and Drug Administration (FDA) has approved the use of Deep Brain Stimulation (DBS) as a brain implant in humans. As for neural implant both the cochlear implant and retinal implant are approved by FDA too. All of them had shown a promising result. DBS worked by stimulating a specific region in the brain with electricity. This device is planted surgically into a very specific region of the brain. This device consists of 3 main parts: Lead (thin wire inserted into the brain), neurostimulator (pacemaker-like device, planted surgically in the chest) and an external controller (to turn on/off the device by patient/programmer). FDA had approved DBS for the treatment of PD, Pain Management, Epilepsy and Obsessive Compulsive Disorder (OCD). The target treatment of DBS in PD is to reduce the tremor and dystonia symptoms. DBS has been showing the promising result in animal and limited human trial for other conditions such as Alzheimer, Mental Health Problem (Major Depression, Tourette Syndrome), etc. Every surgery has risks of complications, although in DBS the chance is very low. DBS itself had a very satisfying result as long as the subject criteria to be implanted this device based on indication and strictly selection. Other than DBS, there are several brain implant devices that still under development. It was included (not limited to) implant to treat paralysis (In Spinal Cord Injury/Amyotrophic Lateral Sclerosis), enhance brain memory, reduce obesity, treat mental health problem and treat epilepsy. The potential of neurotechnology is unlimited. When brain function and brain implant were fully developed, it may be one of the major breakthroughs in human history like when human find ‘fire’ for the first time. Support from every sector for further research is very needed to develop and unveil the true potential of this technology.

Keywords: brain implant, deep brain stimulation (DBS), deep brain stimulation, Parkinson

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16 Dosimetric Comparison among Different Head and Neck Radiotherapy Techniques Using PRESAGE™ Dosimeter

Authors: Jalil ur Rehman, Ramesh C. Tailor, Muhammad Isa Khan, Jahnzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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Purpose: The purpose of this analysis was to investigate dose distribution of different techniques (3D-CRT, IMRT and VMAT) of head and neck cancer using 3-dimensional dosimeter called PRESAGETM Dosimeter. Materials and Methods: Computer tomography (CT) scans of radiological physics center (RPC) head and neck anthropomorphic phantom with both RPC standard insert and PRESAGETM insert were acquired separated with Philipp’s CT scanner and both CT scans were exported via DICOM to the Pinnacle version 9.4 treatment planning system (TPS). Each plan was delivered twice to the RPC phantom first containing the RPC standard insert having TLD and film dosimeters and then again containing the Presage insert having 3-D dosimeter (PRESAGETM) by using a Varian True Beam linear accelerator. After irradiation, the standard insert including point dose measurements (TLD) and planar Gafchromic® EBT film measurement were read using RPC standard procedure. The 3D dose distribution from PRESAGETM was read out with the Duke Midsized optical scanner dedicated to RPC (DMOS-RPC). Dose volume histogram (DVH), mean and maximal doses for organs at risk were calculated and compared among each head and neck technique. The prescription dose was same for all head and neck radiotherapy techniques which was 6.60 Gy/friction. Beam profile comparison and gamma analysis were used to quantify agreements among film measurement, PRESAGETM measurement and calculated dose distribution. Quality assurances of all plans were performed by using ArcCHECK method. Results: VMAT delivered the lowest mean and maximum doses to organ at risk (spinal cord, parotid) than IMRT and 3DCRT. Such dose distribution was verified by absolute dose distribution using thermoluminescent dosimeter (TLD) system. The central axial, sagittal and coronal planes were evaluated using 2D gamma map criteria(± 5%/3 mm) and results were 99.82% (axial), 99.78% (sagital), 98.38% (coronal) for VMAT plan and found the agreement between PRESAGE and pinnacle was better than IMRT and 3D-CRT plan excludes a 7 mm rim at the edge of the dosimeter. Profile showed good agreement for all plans between film, PRESAGE and pinnacle and 3D gamma was performed for PTV and OARs, VMAT and 3DCRT endow with better agreement than IMRT. Conclusion: VMAT delivered lowered mean and maximal doses to organs at risk and better PTV coverage during head and neck radiotherapy. TLD, EBT film and PRESAGETM dosimeters suggest that VMAT was better for the treatment of head and neck cancer than IMRT and 3D-CRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD, PRESAGETM

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15 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

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The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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14 A 3d Intestine-On-Chip Model Allows Colonization with Commensal Bacteria to Study Host-Microbiota Interaction

Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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13 Knowledge, Attitudes, and Practices of Army Soldiers on Prehospital Trauma Care in Matara District

Authors: Hatharasinghe Liyanage Saneetha Chathaurika, Shreenika De Silva Weliange

Abstract:

Background and Significance of the Study: Natural and human-induced disasters have become more common due to rapid development and climate change. Therefore hospitalization due to injuries has increased in the midst of advancement in medicine. Prehospital trauma care is critical in reducing morbidity and mortality following injury. Army soldiers are one of the first responder categories after a major disaster causing injury. Thus, basic life support measures taken by trained lay first responders is life-saving, it is important to build up their capacities by updating their knowledge and practices while cultivating positive attitudes toward it. Objective: To describe knowledge, attitudes and practices on prehospital trauma care among army soldiers in Matara District. Methodology: A descriptive cross sectional study was carried out among army soldiers in Matara district. The whole population was studied belonging to the above group during the study period. Self-administered questionnaire was used as the study instrument. Cross tabulations were done to identify the possible associations using chi square statistics. Knowledge and practices were categorized in to two groups as “Poor” and “Good” taking 50% as the cut off. Results: The study population consists of 266 participants (response rate 97.79%).The overall level of knowledge on prehospital trauma care is poor (78.6%) while knowledge on golden hour of trauma (77.1%), triage system (74.4%), cardio pulmonary resuscitation (92.5%) and transportation of patients with spinal cord injury (69.2%) was markedly poor. Good knowledge is significantly associated with advance age, higher income and higher level of education whereas it has no significant association with work duration. More than 80% of them had positive attitudes on most aspects of prehospital trauma care while majority thinks it is good to have knowledge on this topic and they would have performed better in disaster situations if they were trained on pre-hospital trauma care. With regard to the practice, majority (62.8%) is included in the group of poor level of practice. They lack practice on first-aid, cardiopulmonary resuscitation and safe transportation of the patients. Moreover, they had less opportunity to participate in drills/simulation programs done on disaster events. Good practice is significantly associated with advance age and higher level of education but not associated with level of income and working duration of army soldiers. Highly significant association was observed between the level of knowledge and level of practice on prehospital trauma care of army soldiers. It is observed that higher the knowledge practices become better. Conclusion: A higher proportion of army soldiers had poor knowledge and practice on prehospital trauma care while majority had positive attitudes regarding it. Majority lacks knowledge and practice in first-aid and cardiopulmonary resuscitation. Due to significant association observed between knowledge and practice it can be recommended to include a training session on prehospital trauma care in the basic military curriculum which will enhance the ability to act as first responders effectively. Further research is needed in this area of prehospital trauma care to enhance the qualitative outcome.

Keywords: disaster, prehospital trauma care, first responders, army soldiers

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12 Analysis of Stress and Strain in Head Based Control of Cooperative Robots through Tetraplegics

Authors: Jochen Nelles, Susanne Kohns, Julia Spies, Friederike Schmitz-Buhl, Roland Thietje, Christopher Brandl, Alexander Mertens, Christopher M. Schlick

Abstract:

Industrial robots as part of highly automated manufacturing are recently developed to cooperative (light-weight) robots. This offers the opportunity of using them as assistance robots and to improve the participation in professional life of disabled or handicapped people such as tetraplegics. Robots under development are located within a cooperation area together with the working person at the same workplace. This cooperation area is an area where the robot and the working person can perform tasks at the same time. Thus, working people and robots are operating in the immediate proximity. Considering the physical restrictions and the limited mobility of tetraplegics, a hands-free robot control could be an appropriate approach for a cooperative assistance robot. To meet these requirements, the research project MeRoSy (human-robot synergy) develops methods for cooperative assistance robots based on the measurement of head movements of the working person. One research objective is to improve the participation in professional life of people with disabilities and, in particular, mobility impaired persons (e.g. wheelchair users or tetraplegics), whose participation in a self-determined working life is denied. This raises the research question, how a human-robot cooperation workplace can be designed for hands-free robot control. Here, the example of a library scenario is demonstrated. In this paper, an empirical study that focuses on the impact of head movement related stress is presented. 12 test subjects with tetraplegia participated in the study. Tetraplegia also known as quadriplegia is the worst type of spinal cord injury. In the experiment, three various basic head movements were examined. Data of the head posture were collected by a motion capture system; muscle activity was measured via surface electromyography and the subjective mental stress was assessed via a mental effort questionnaire. The muscle activity was measured for the sternocleidomastoid (SCM), the upper trapezius (UT) or trapezius pars descendens, and the splenius capitis (SPL) muscle. For this purpose, six non-invasive surface electromyography sensors were mounted on the head and neck area. An analysis of variance shows differentiated muscular strains depending on the type of head movement. Systematically investigating the influence of different basic head movements on the resulting strain is an important issue to relate the research results to other scenarios. At the end of this paper, a conclusion will be drawn and an outlook of future work will be presented.

Keywords: assistance robot, human-robot interaction, motion capture, stress-strain-concept, surface electromyography, tetraplegia

Procedia PDF Downloads 288
11 An Australian Tertiary Centre Experience of Complex Endovascular Aortic Repairs

Authors: Hansraj Bookun, Rachel Xuan, Angela Tan, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos, Jim Iliopoulos

Abstract:

Introduction: Complex endovascular aortic aneursymal repairs with fenestrated and branched endografts require customised devices to exclude the pathology while reducing morbidity and mortality, which was historically associated with open repair of complex aneurysms. Such endovascular procedures have predominantly been performed in a large volume dedicated tertiary centres. We present here our nine year multidisciplinary experience with this technology in an Australian tertiary centre. Method: This was a cross-sectional, single-centre observational study of 670 patients who had undergone complex endovascular aortic aneurysmal repairs with conventional endografts, fenestrated endografts, and iliac-branched devices from January 2010 to July 2019. Descriptive statistics were used to characterise our sample with regards to demographic and perioperative variables. Homogeneity of the sample was tested using multivariant regression, which did not identify any statistically significant confounding variables. Results: 670 patients of mean age 74, were included (592 males) and the comorbid burden was as follows: ischemic heart disease (55%), diabetes (18%), hypertension (90%), stage four or greater kidney impairment (8%) and current or ex-smoking (78%). The main indications for surgery were elective aneurysms (86%), symptomatic aneurysms (5%), and rupture aneurysms (5%). 106 patients (16%) underwent fenestrated or branched endograft repairs. The mean length of stay was 7.6 days. 2 patients experienced reactionary bleeds, 11 patients had access wound complications (6 lymph fistulae, 5 haematoms), 11 patients had cardiac complications (5 arrhythmias, 3 acute myocadial infarctions, 3 exacerbation of congestive cardiac failure), 10 patients had respiratory complications, 8 patients had renal impairment, 4 patients had gastrointestinal complications, 2 patients suffered from paraplegia, 1 major stroke, 1 minor stroke, and 1 acute brain syndrome. There were 4 vascular occlusions requiring further arterial surgery, 4 type I endoleaks, 4 type II endoleaks, 3 episodes of thromboembolism, and 2 patients who required further arterial operations in the setting of patient vessels. There were 9 unplanned returns to the theatre. Discussion: Our numbers of 10 years suggest that we are not a dedicated high volume centre focusing on aortic repairs. However, we have achieved significantly low complication rates. This can be attributed to our multidisciplinary approach with the intraoperative involvement of skilled interventional radiologists and vascular surgeons as well as postoperative protocols with particular attention to spinal cord protection. Additionally, we have a ratified perioperative pathway that involves multidisciplinary team discussions of patient-related factors and lesion-centered characteristics, which allows for holistic, patient-centered care.

Keywords: aneurysm, aortic, endovascular, fenestrated

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10 Development of Chitosan/Dextran Gelatin Methacrylate Core/Shell 3D Scaffolds and Protein/Polycaprolactone Melt Electrowriting Meshes for Tissue Regeneration Applications

Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

Abstract:

Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

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9 Development of Three-Dimensional Bio-Reactor Using Magnetic Field Stimulation to Enhance PC12 Cell Axonal Extension

Authors: Eiji Nakamachi, Ryota Sakiyama, Koji Yamamoto, Yusuke Morita, Hidetoshi Sakamoto

Abstract:

The regeneration of injured central nerve network caused by the cerebrovascular accidents is difficult, because of poor regeneration capability of central nerve system composed of the brain and the spinal cord. Recently, new regeneration methods such as transplant of nerve cells and supply of nerve nutritional factor were proposed and examined. However, there still remain many problems with the canceration of engrafted cells and so on and it is strongly required to establish an efficacious treating method of a central nerve system. Blackman proposed the electromagnetic stimulation method to enhance the axonal nerve extension. In this study, we try to design and fabricate a new three-dimensional (3D) bio-reactor, which can load a uniform AC magnetic field stimulation on PC12 cells in the extracellular environment for enhancement of an axonal nerve extension and 3D nerve network generation. Simultaneously, we measure the morphology of PC12 cell bodies, axons, and dendrites by the multiphoton excitation fluorescence microscope (MPM) and evaluate the effectiveness of the uniform AC magnetic stimulation to enhance the axonal nerve extension. Firstly, we designed and fabricated the uniform AC magnetic field stimulation bio-reactor. For the AC magnetic stimulation system, we used the laminated silicon steel sheets for a yoke structure of 3D chamber, which had a high magnetic permeability. Next, we adopted the pole piece structure and installed similar specification coils on both sides of the yoke. We searched an optimum pole piece structure using the magnetic field finite element (FE) analyses and the response surface methodology. We confirmed that the optimum 3D chamber structure showed a uniform magnetic flux density in the PC12 cell culture area by using FE analysis. Then, we fabricated the uniform AC magnetic field stimulation bio-reactor by adopting analytically determined specifications, such as the size of chamber and electromagnetic conditions. We confirmed that measurement results of magnetic field in the chamber showed a good agreement with FE results. Secondly, we fabricated a dish, which set inside the uniform AC magnetic field stimulation of bio-reactor. PC12 cells were disseminated with collagen gel and could be 3D cultured in the dish. The collagen gel were poured in the dish. The collagen gel, which had a disk shape of 6 mm diameter and 3mm height, was set on the membrane filter, which was located at 4 mm height from the bottom of dish. The disk was full filled with the culture medium inside the dish. Finally, we evaluated the effectiveness of the uniform AC magnetic field stimulation to enhance the nurve axonal extension. We confirmed that a 6.8 increase in the average axonal extension length of PC12 under the uniform AC magnetic field stimulation at 7 days culture in our bio-reactor, and a 24.7 increase in the maximum axonal extension length. Further, we confirmed that a 60 increase in the number of dendrites of PC12 under the uniform AC magnetic field stimulation. Finally, we confirm the availability of our uniform AC magnetic stimulation bio-reactor for the nerve axonal extension and the nerve network generation.

Keywords: nerve regeneration, axonal extension , PC12 cell, magnetic field, three-dimensional bio-reactor

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8 Design of Ultra-Light and Ultra-Stiff Lattice Structure for Performance Improvement of Robotic Knee Exoskeleton

Authors: Bing Chen, Xiang Ni, Eric Li

Abstract:

With the population ageing, the number of patients suffering from chronic diseases is increasing, among which stroke is a high incidence for the elderly. In addition, there is a gradual increase in the number of patients with orthopedic or neurological conditions such as spinal cord injuries, nerve injuries, and other knee injuries. These diseases are chronic, with high recurrence and complications, and normal walking is difficult for such patients. Nowadays, robotic knee exoskeletons have been developed for individuals with knee impairments. However, the currently available robotic knee exoskeletons are generally developed with heavyweight, which makes the patients uncomfortable to wear, prone to wearing fatigue, shortening the wearing time, and reducing the efficiency of exoskeletons. Some lightweight materials, such as carbon fiber and titanium alloy, have been used for the development of robotic knee exoskeletons. However, this increases the cost of the exoskeletons. This paper illustrates the design of a new ultra-light and ultra-stiff truss type of lattice structure. The lattice structures are arranged in a fan shape, which can fit well with circular arc surfaces such as circular holes, and it can be utilized in the design of rods, brackets, and other parts of a robotic knee exoskeleton to reduce the weight. The metamaterial is formed by continuous arrangement and combination of small truss structure unit cells, which changes the diameter of the pillar section, geometrical size, and relative density of each unit cell. It can be made quickly through additive manufacturing techniques such as metal 3D printing. The unit cell of the truss structure is small, and the machined parts of the robotic knee exoskeleton, such as connectors, rods, and bearing brackets, can be filled and replaced by gradient arrangement and non-uniform distribution. Under the condition of satisfying the mechanical properties of the robotic knee exoskeleton, the weight of the exoskeleton is reduced, and hence, the patient’s wearing fatigue is relaxed, and the wearing time of the exoskeleton is increased. Thus, the efficiency and wearing comfort, and safety of the exoskeleton can be improved. In this paper, a brief description of the hardware design of the prototype of the robotic knee exoskeleton is first presented. Next, the design of the ultra-light and ultra-stiff truss type of lattice structures is proposed, and the mechanical analysis of the single-cell unit is performed by establishing the theoretical model. Additionally, simulations are performed to evaluate the maximum stress-bearing capacity and compressive performance of the uniform arrangement and gradient arrangement of the cells. Finally, the static analysis is performed for the cell-filled rod and the unmodified rod, respectively, and the simulation results demonstrate the effectiveness and feasibility of the designed ultra-light and ultra-stiff truss type of lattice structures. In future studies, experiments will be conducted to further evaluate the performance of the designed lattice structures.

Keywords: additive manufacturing, lattice structures, metamaterial, robotic knee exoskeleton

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7 Safety of Mesenchymal Stem Cells Therapy: Potential Risk of Spontaneous Transformations

Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

Abstract:

Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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6 Targeting Tumour Survival and Angiogenic Migration after Radiosensitization with an Estrone Analogue in an in vitro Bone Metastasis Model

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

Abstract:

Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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5 Sublethal Effects of Industrial Effluents on Fish Fingerlings (Clarias gariepinus) from Ologe Lagoon Environs, Lagos, Nigeria

Authors: Akintade O. Adeboyejo, Edwin O. Clarke, Oluwatoyin Aderinola

Abstract:

The present study is on the sub-lethal toxicity of industrial effluents (IE) from the environment of Ologe Lagoon, Lagos, Nigeria on the African catfish fingerlings Clarias gariepinus. The fish were cultured in varying concentrations of industrial effluents: 0% (control), 5%, 15%, 25%, and 35%. Trials were carried out in triplicates for twelve (12) weeks. The culture system was a static renewable bioassay and was carried out in the fisheries laboratory of the Lagos State University, Ojo-Lagos. Weekly physico-chemical parameters: Temperature (0C), pH, Conductivity (ppm) and Dissolved Oxygen (DO in mg/l) were measured in each treatment tank. Length (cm) and weight (g) data were obtained weekly and used to calculate various growth parameters: mean weight gain (MWG), percentage weight gain (PWG), daily weight gain (DWG), specific growth rate (SGR) and survival. Haematological (Packed Cell Volume (PCV), Red blood cells (RBC), White Blood Cell (WBC), Neutrophil and Lymphocytes etc) and histological alterations were measured after 12 weeks. The physico-chemical parameters showed that the pH ranged from 7.82±0.25–8.07±0.02. DO range from 1.92±0.66-4.43±1.24 mg/l. The conductivity values increased with increase in concentration of I.E. While the temperature remained stable with mean value range between 26.08±2.14–26.38±2.28. The DO showed significant differences at P<0.05. There was progressive increase in length and weight of fish during the culture period. The fish placed in the control had highest increase in both weight and length while fish in 35% had the least. MWG ranged from 16.59–35.96, DWG is from 0.3–0.48, SGR varied from 1.0–1.86 and survival was 100%. Haematological results showed that C. gariepinus had PCV ranging from 13.0±1.7-27.7±0.6, RBC ranged from 4.7±0.6–9.1±0.1, and Neutrophil ranged from 26.7±4.6–61.0±1.0 amongst others. The highest values of these parameters were obtained in the control and lowest at 35%. While the reverse effects were observed for WBC and lymphocytes. This study has shown that effluents may affect the health status of the test organism and impair vital processes if exposure continues for a long period of time. The histological examination revealed several lesions as expressed by the gills and livers. The histopathology of the gills in the control tanks had normal tissues with no visible lesion, but at higher concentrations, there were: lifting of epithelium, swollen lamellae and gill arch infiltration, necrosis and gill arch destruction. While in the liver: control (0%) show normal liver cells, at higher toxic level, there were: vacoulation, destruction of the hepatic parenchyma, tissue becoming eosinophilic (i.e. tending towards Carcinogenicity) and severe disruption of the hepatic cord architecture. The study has shown that industrial effluents from the study area may affect fish health status and impair vital processes if exposure continues for a long period of time even at lower concentrations (Sublethal).

Keywords: sublethal toxicity, industrial effluents, clarias gariepinus, ologe lagoon

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4 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line

Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

Abstract:

Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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3 Functional Outcome of Speech, Voice and Swallowing Following Excision of Glomus Jugulare Tumor

Authors: B. S. Premalatha, Kausalya Sahani

Abstract:

Background: Glomus jugulare tumors arise within the jugular foramen and are commonly seen in females particularly on the left side. Surgical excision of the tumor may cause lower cranial nerve deficits. Cranial nerve involvement produces hoarseness of voice, slurred speech, and dysphagia along with other physical symptoms, thereby affecting the quality of life of individuals. Though oncological clearance is mainly emphasized on while treating these individuals, little importance is given to their communication, voice and swallowing problems, which play a crucial part in daily functioning. Objective: To examine the functions of voice, speech and swallowing outcomes of the subjects, following excision of glomus jugulare tumor. Methods: Two female subjects aged 56 and 62 years had come with a complaint of change in voice, inability to swallow and reduced clarity of speech following surgery for left glomus jugulare tumor were participants of the study. Their surgical information revealed multiple cranial nerve palsies involving the left facial, left superior and recurrent branches of the vagus nerve, left pharyngeal, left soft palate, left hypoglossal and vestibular nerves. Functional outcomes of voice, speech and swallowing were evaluated by perceptual and objective assessment procedures. Assessment included the examination of oral structures and functions, dysarthria by Frenchey dysarthria assessment, cranial nerve functions and swallowing functions. MDVP and Dr. Speech software were used to evaluate acoustic parameters of voice and quality of voice respectively. Results: The study revealed that both the subjects, subsequent to excision of glomus jugulare tumor, showed a varied picture of affected oral structure and functions, articulation, voice and swallowing functions. The cranial nerve assessment showed impairment of the vagus, hypoglossal, facial and glossopharyngeal nerves. Voice examination indicated vocal cord paralysis associated with breathy quality of voice, weak voluntary cough, reduced pitch and loudness range, and poor respiratory support. Perturbation parameters as jitter, shimmer were affected along with s/z ratio indicative of voice fold pathology. Reduced MPD(Maximum Phonation Duration) of vowels indicated that disturbed coordination between respiratory and laryngeal systems. Hypernasality was found to be a prominent feature which reduced speech intelligibility. Imprecise articulation was seen in both the subjects as the hypoglossal nerve was affected following surgery. Injury to vagus, hypoglossal, gloss pharyngeal and facial nerves disturbed the function of swallowing. All the phases of swallow were affected. Aspiration was observed before and during the swallow, confirming the oropharyngeal dysphagia. All the subsystems were affected as per Frenchey Dysarthria Assessment signifying the diagnosis of flaccid dysarthria. Conclusion: There is an observable communication and swallowing difficulty seen following excision of glomus jugulare tumor. Even with complete resection, extensive rehabilitation may be necessary due to significant lower cranial nerve dysfunction. The finding of the present study stresses the need for involvement of as speech and swallowing therapist for pre-operative counseling and assessment of functional outcomes.

Keywords: functional outcome, glomus jugulare tumor excision, multiple cranial nerve impairment, speech and swallowing

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2 Anesthesia for Spinal Stabilization Using Neuromuscular Blocking Agents in Dog: Case Report

Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

Abstract:

Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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1 Probability Modeling and Genetic Algorithms in Small Wind Turbine Design Optimization: Mentored Interdisciplinary Undergraduate Research at LaGuardia Community College

Authors: Marina Nechayeva, Malgorzata Marciniak, Vladimir Przhebelskiy, A. Dragutan, S. Lamichhane, S. Oikawa

Abstract:

This presentation is a progress report on a faculty-student research collaboration at CUNY LaGuardia Community College (LaGCC) aimed at designing a small horizontal axis wind turbine optimized for the wind patterns on the roof of our campus. Our project combines statistical and engineering research. Our wind modeling protocol is based upon a recent wind study by a faculty-student research group at MIT, and some of our blade design methods are adopted from a senior engineering project at CUNY City College. Our use of genetic algorithms has been inspired by the work on small wind turbines’ design by David Wood. We combine these diverse approaches in our interdisciplinary project in a way that has not been done before and improve upon certain techniques used by our predecessors. We employ several estimation methods to determine the best fitting parametric probability distribution model for the local wind speed data obtained through correlating short-term on-site measurements with a long-term time series at the nearby airport. The model serves as a foundation for engineering research that focuses on adapting and implementing genetic algorithms (GAs) to engineering optimization of the wind turbine design using Blade Element Momentum Theory. GAs are used to create new airfoils with desirable aerodynamic specifications. Small scale models of best performing designs are 3D printed and tested in the wind tunnel to verify the accuracy of relevant calculations. Genetic algorithms are applied to selected airfoils to determine the blade design (radial cord and pitch distribution) that would optimize the coefficient of power profile of the turbine. Our approach improves upon the traditional blade design methods in that it lets us dispense with assumptions necessary to simplify the system of Blade Element Momentum Theory equations, thus resulting in more accurate aerodynamic performance calculations. Furthermore, it enables us to design blades optimized for a whole range of wind speeds rather than a single value. Lastly, we improve upon known GA-based methods in that our algorithms are constructed to work with XFoil generated airfoils data which enables us to optimize blades using our own high glide ratio airfoil designs, without having to rely upon available empirical data from existing airfoils, such as NACA series. Beyond its immediate goal, this ongoing project serves as a training and selection platform for CUNY Research Scholars Program (CRSP) through its annual Aerodynamics and Wind Energy Research Seminar (AWERS), an undergraduate summer research boot camp, designed to introduce prospective researchers to the relevant theoretical background and methodology, get them up to speed with the current state of our research, and test their abilities and commitment to the program. Furthermore, several aspects of the research (e.g., writing code for 3D printing of airfoils) are adapted in the form of classroom research activities to enhance Calculus sequence instruction at LaGCC.

Keywords: engineering design optimization, genetic algorithms, horizontal axis wind turbine, wind modeling

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