Search results for: brain implant

Authors: Jer Ping Ooi, Shah Rizal Bin Kasim, Nor Aini Saidin

Abstract:

The objective of this study was to synthesize nano-sized β-tricalcium phosphate (β-TCP) powder and assess its cytotoxic effects on human osteoblast (hFOB1.19) by using four cytotoxicity assays, namely, lactose dehydrogenase (LDHe), tetrazolium hydroxide (XTT), neutral red (NR), and sulforhodamine B (SRB) assays. β-tricalcium phosphate (β-TCP) is a calcium phosphate compound commonly used as an implant material. To date, bulk-sized β-TCP is reported to be readily tolerated by the osteogenic cells and body based on in vitro, in vivo experiments and clinical studies. However, to what extent of nano-sized β-TCP will react in models as compared to bulk β-TCP is yet to be investigated. Thus, in this project, the cells were treated with nano β-TCP powder within a range of concentrations from 0 to 1000 μg/mL for 24, 48, and 72 h. The cytotoxicity tests showed that loss of cell viability ( > 50%) was high for hFOB1.19 cells in all assays. Cell cycle and apoptosis analysis of hFOB1.19 cells revealed that 50 μg/mL of the compound led to 30.5% of cells being apoptotic after 72 h of incubation, and the percentage was increased to 58.6% when the concentration was increased to 200 μg/mL. When the incubation time was increased from 24 to 72 h, the percentage of apoptotic cells increased from 17.3% to 58.6% when the hFOB1.19 were exposed with 200 μg/mL of nano β-TCP powder. Thus, both concentration and exposure duration affected the cytotoxicity effects of the nano β-TCP powder on hFOB1.19. We hypothesize that these cytotoxic effects on hFOB1.19 are related to the nano-scale size of the β-TCP.

Keywords: β-tricalcium phosphate, hFOB1.19, adipose-derived mesenchymal stem cells, cytotoxicity

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Authors: A. Mohamed, A. El-Aziz

Abstract:

The pH of the body plays a great role in the degradation kinetics of biodegradable Mg-Ca orthopedic implants. At the location of fracture, the pH of the body becomes no longer neutral which draws the attention towards studying a range of different pH values of the body fluid. In this study, the pH of Hank’s balanced salt solution (HBSS) was modified by phosphate buffers into an aggressive acidic pH 1.8, a slightly acidic pH 5.3 and an alkaline pH 8.1. The biodegradation of Mg-0.8Ca implant was tested in those three different media using immersion test and electrochemical polarization means. It was proposed that the degradation rate has increased with decreasing the pH of HBSS. The immersion test revealed weight gain for all the samples followed by weight loss as the immersion time increased. The highest weight gain was pronounced for the acidic pH 1.8 and the least weight gain was observed for the alkaline pH 8.1. This was in agreement with the electrochemical polarization test results where the degradation rate was found to be high (7.29 ± 2.2 mm/year) in the aggressive acidic solution of pH 1.8 and relatively minimum (0.31 ± 0.06 mm/year) in the alkaline medium of pH 8.1. Furthermore, it was confirmed that the pH of HBSS has reached a steady state of an alkaline pH (~pH 11) at the end of the two-month immersion period regardless of the initial pH of the solution. Finally, the corrosion products formed on the samples’ surface were investigated by SEM, EDX and XRD analyses that revealed the formation of magnesium and calcium phosphates with different morphologies according to the pH.

Keywords: biodegradable, electrochemical polarization means, orthopedics, immersion test, simulated body fluid

Procedia PDF Downloads 116

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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Authors: Mikel Alonso López

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In the first decade of the twenty-first century, advanced imaging techniques began to be applied for neuroscience research. The Functional Magnetic Resonance Imaging (fMRI) is one of the most important and most used research techniques for the investigation of emotions, because of its ease to observe the brain areas that oxygenate when performing certain tasks. In this research, we make a review about the main research carried out on the influence of the emotions in the decision-making process that is exposed by using the fMRI.

Keywords: decision making, emotions, fMRI, consumer behaviour

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

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

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

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Authors: Rai Sachindra Prasad

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Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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Authors: Tran Thi Anh Dao, M. Arnold, L. Schacher, D. C. Adolphe, G. Reys

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During tooth extraction or implant surgery, dentists are in contact with numerous infectious germs from patients' saliva and blood. For that reason, dentist's clothes have to play their role of protection from contamination. In addition, dentist's apparels should be not only protective but also comfortable and breathable because dentists have to perform many operations and treatments on patients throughout the day with high concentration and intensity. However, this type of protective garments has not been studied scientifically, whereas dentists are facing new risks and eager for looking for a comfortable personal protective equipment. For that reason, we have proposed some new designs of dentist's gown. They were expected to diminish heat accumulation that are considered as an important factor in reducing the level of comfort experienced by users. Experiments using infra-red technology were carried out in order to compare the breathable properties between a traditional gown and a new design with open zones. Another experiment using pressure sensors was also carried out to study ergonomic aspects trough the flexibility of movements of sleeves. The sleeves-design which is considered comfortable and flexible will be chosen for the further step. The results from the two experiments provide valuable information for the development of a new design of dentists' gowns in order to achieve maximum levels of cooling and comfort for the human body.

Keywords: garment, dentists, comfort, design, protection, thermal

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Authors: L. Siva Rama Krishna, Sriram Venkatesh, M. Sastish Kumar, M. Uma Maheswara Chary

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Rapid Prototyping (RP) is a technology that produces models and prototype parts from 3D CAD model data, CT/MRI scan data, and model data created from 3D object digitizing systems. There are several RP process like Stereolithography (SLA), Solid Ground Curing (SGC), Selective Laser Sintering (SLS), Fused Deposition Modelling (FDM), 3D Printing (3DP) among them SLS and FDM RP processes are used to fabricate pattern of custom cranial implant. RP technology is useful in engineering and biomedical application. This is helpful in engineering for product design, tooling and manufacture etc. RP biomedical applications are design and development of medical devices, instruments, prosthetics and implantation; it is also helpful in planning complex surgical operation. The traditional approach limits the full appreciation of various bony structure movements and therefore the custom implants produced are difficult to measure the anatomy of parts and analyse the changes in facial appearances accurately. Cranioplasty surgery is a surgical correction of a defect in cranial bone by implanting a metal or plastic replacement to restore the missing part. This paper aims to do a comparative study on the dimensional error of CAD and SLS RP Models for reconstruction of cranial defect by comparing the virtual CAD with the physical RP model of a cranial defect.

Keywords: rapid prototyping, selective laser sintering, cranial defect, dimensional error

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Authors: Sylwia Baluta, Joanna Cabaj, Karol Malecha

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The evolution of biosensors was driven by the need for faster and more versatile analytical methods for application in important areas including clinical, diagnostics, food analysis or environmental monitoring, with minimum sample pretreatment. Rapid and sensitive neurotransmitters detection is extremely important in modern medicine. These compounds mainly occur in the brain and central nervous system of mammals. Any changes in the neurotransmitters concentration may lead to many diseases, such as Parkinson’s or schizophrenia. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements.

Keywords: adrenaline, biosensor, dopamine, laccase, tyrosinase

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Authors: Emhimed Saffor

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In this paper, the problem of edge detection in digital images is considered. Three methods of edge detection based on mathematical morphology algorithm were applied on two sets (Brain and Chest) CT images. 3x3 filter for first method, 5x5 filter for second method and 7x7 filter for third method under MATLAB programming environment. The results of the above-mentioned methods are subjectively evaluated. The results show these methods are more efficient and satiable for medical images, and they can be used for different other applications.

Keywords: CT images, Matlab, medical images, edge detection

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Authors: Khurram Munir, Cuie Wen, Yuncang Li

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Magnesium (Mg) metal matrix composites (MMCs) reinforced with graphene nanoplatelets (GNPs) have been developed by powder metallurgy (PM). In this study, GNPs with different concentrations (0.1-0.3 wt.%) were dispersed into Mg powders by high-energy ball-milling processes. The microstructure and resultant mechanical properties of the fabricated nanocomposites were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Raman spectroscopy (RS), compression and nano-wear tests. The corrosion resistance of the fabricated composites was evaluated by electrochemical tests and hydrogen evolution measurements. Finally, the biological response of Mg-GNPs composites was assessed using osteoblast-like SaOS2 cells. The results indicate that GNPs are excellent candidates as reinforcements in Mg matrices for the manufacture of biodegradable Mg-based composite implants. GNP addition improved the mechanical properties of Mg via synergetic strengthening modes. Moreover, retaining the structural integrity of GNPs during PM processing improved the ductility, compressive strength, and corrosion resistance of the Mg-GNP composites as compared to monolithic Mg. Cytotoxicity assessments did not reveal any significant toxicity with the addition of GNPs to Mg matrices. This study demonstrates that Mg-xGNPs with x < 0.3 wt.%, may constitute novel biodegradable implant materials for load-bearing applications.

Keywords: magnesium-graphene composites, strengthening mechanisms, In vitro cytotoxicity, biocorrosion

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Authors: Tamer Mesallam, Medhat Yousef, Ayna Almasaad

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BACKGROUND: Cochlear implantation (CI) in children with additional disabilities can be a fundamental and supportive intervention. Although, there may be some positive impacts of CI on children with multiple disabilities such as better outcomes of communication skills, development, and quality of life, the families of those children complain from the post-implant habilitation efforts that considered as a burden. OBJECTIVE: To investigate the outcomes of CI children with different co-disabilities through using the Meaningful Auditory Integration Scale (MAIS) and the Meaningful Use of Speech Scale (MUSS) as outcome measurement tools. METHODS: The study sample comprised 25 hearing-impaired children with co-disability who received cochlear implantation. Age and gender-matched control group of 25 cochlear-implanted children without any other disability has been also included. The participants' auditory skills and speech outcomes were assessed using MAIS and MUSS tests. RESULTS: There was a statistically significant difference in the different outcomes measure between the two groups. However, the outcomes of some multiple disabilities subgroups were comparable to the control group. Around 40% of the participants with co-disabilities experienced advancement in their methods of communication from behavior to oral mode. CONCLUSION: Cochlear-implanted children with multiple disabilities showed variable degrees of auditory and speech outcomes. The degree of benefits depends on the type of the co-disability. Long-term follow-up is recommended for those children.

Keywords: children with disabilities, Cochlear implants, hearing impairment, language development

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Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

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Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

Procedia PDF Downloads 56

Authors: Carolina Pereira Lobato Costa, Cristina Pascual-González, Monica Echeverry, Javier LLorca, Carlos Gonzáléz, Juan Pedro Fernández-Bláquez

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Although the potential of PLA self-reinforced composites for bone applications, not much literature addresses optimal manufacturing conditions. In this regard, this paper describes the woven self-reinforced PLA composites manufacturing processes: the commingling of yarns, weaving, and hot pressing and characterizes the manufactured laminates. Different structures and properties can be achieved by varying the hot compaction process parameters (pressure, holding time, and temperature). The specimens manufactured were characterized in terms of thermal properties (DSC), microstructure (C-scan optical microscope and SEM), strength (tensile test), and biocompatibility (MTT assays). Considering the final device, 155 ℃ for 10 min at 2 MPa act as the more appropriate hot pressing parameters. The laminate produced with these conditions has few voids/porosity, a tensile strength of 30.39 ± 1.21 MPa, and a modulus of 4.09 ± 0.24 GPa. Subsequently to the tensile testing was possible to observe fiber pullout from the fracture surfaces, confirming that this material behaves as a composite. From the results, no single laminate can fulfill all the requirements, being necessary to compromise in function of the priority property. Further investigation is required to improve materials' mechanical performance. Subsequently, process parameters and materials configuration can be adjusted depending on the place and type of implant to suit its function.

Keywords: woven fabric, self-reinforced polymer composite, poly(lactic acid), biodegradable

Procedia PDF Downloads 187

Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

Procedia PDF Downloads 89

Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer

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This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.

Keywords: communication, cooperation, development, interaction, neuroscience

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Authors: Sylvia Nkiru Ogbuoji

Abstract:

This paper discussed the consequences of inadequate funding in Nigerian education system. It briefly explained the meaning of education in relation to the context and identified various ways education in Nigeria can be funded. It highlighted some of the consequences of inadequate funding education system to include: Inadequate facilitates for teaching and learning, western brain drain, unemployment, crises of poverty, low staff morale it. Finally, some recommendations were put forward, the government should improve the annual budget allocation to education, in order to achieve educational objective, also government should monitor the utilization of allocated funds to minimize embezzlement.

Keywords: consequences, corruption, education, funding

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Authors: Lev Bertovsky

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The purpose of this study was to determine the reasons for the formation of false testimony from witnesses and make recommendations on the recognition of such cases. During the studies, which were based on the achievements of professionals in the field of psychology, as well as personal investigative practice, the stages of perception of the information were studied, as well as the process of its reclaim from the memory and transmission to the communicator upon request. Based on the principles of the human brain, kinds of conscientious witness mistakes were systematized. Proposals were formulated for the optimization of investigative actions in cases where the witnesses make an honest mistake with respect to the effects previously observed by them.

Keywords: criminology, eyewitness testimony, honest mistake, information, investigator, investigation, questioning

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Authors: Mohammad Zavid Parvez, Manoranjan Paul

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A seizure prediction method is proposed by extracting global features using phase correlation between adjacent epochs for detecting relative changes and local features using fluctuation/deviation within an epoch for determining fine changes of different EEG signals. A classifier and a regularization technique are applied for the reduction of false alarms and improvement of the overall prediction accuracy. The experiments show that the proposed method outperforms the state-of-the-art methods and provides high prediction accuracy (i.e., 97.70%) with low false alarm using EEG signals in different brain locations from a benchmark data set.

Keywords: Epilepsy, seizure, phase correlation, fluctuation, deviation.

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Authors: Rutej R. Mehta, Michael A. Chappell

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Introduction: Arterial spin labelling (ASL) is an increasingly popular perfusion MRI technique, in which arterial blood water is magnetically labelled in the neck before flowing into the brain, providing a non-invasive measure of cerebral blood flow (CBF). The accuracy of ASL CBF measurements, however, is hampered by dispersion effects; the distortion of the ASL labelled bolus during its transit through the vasculature. In spite of this, the current recommended implementation of ASL – the white paper (Alsop et al., MRM, 73.1 (2015): 102-116) – does not account for dispersion, which leads to the introduction of errors in CBF. Given that the transport time from the labelling region to the tissue – the arterial transit time (ATT) – depends on the region of the brain and the condition of the patient, it is likely that these errors will also vary with the ATT. In this study, various dispersion models are assessed in comparison with the white paper (WP) formula for CBF quantification, enabling the errors introduced by the WP to be quantified. Additionally, this study examines the relationship between the errors associated with the WP and the ATT – and how this is influenced by dispersion. Methods: Data were simulated using the standard model for pseudo-continuous ASL, along with various dispersion models, and then quantified using the formula in the WP. The ATT was varied from 0.5s-1.3s, and the errors associated with noise artefacts were computed in order to define the concept of significant error. The instantaneous slope of the error was also computed as an indicator of the sensitivity of the error with fluctuations in ATT. Finally, a regression analysis was performed to obtain the mean error against ATT. Results: An error of 20.9% was found to be comparable to that introduced by typical measurement noise. The WP formula was shown to introduce errors exceeding 20.9% for ATTs beyond 1.25s even when dispersion effects were ignored. Using a Gaussian dispersion model, a mean error of 16% was introduced by using the WP, and a dispersion threshold of σ=0.6 was determined, beyond which the error was found to increase considerably with ATT. The mean error ranged from 44.5% to 73.5% when other physiologically plausible dispersion models were implemented, and the instantaneous slope varied from 35 to 75 as dispersion levels were varied. Conclusion: It has been shown that the WP quantification formula holds only within an ATT window of 0.5 to 1.25s, and that this window gets narrower as dispersion occurs. Provided that the dispersion levels fall below the threshold evaluated in this study, however, the WP can measure CBF with reasonable accuracy if dispersion is correctly modelled by the Gaussian model. However, substantial errors were observed with other common models for dispersion with dispersion levels similar to those that have been observed in literature.

Keywords: arterial spin labelling, dispersion, MRI, perfusion

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: To describe a novel technique of trabeculectomy targeting triple modulation on wound healing to increase the overall success rate. Method: Ten eyes of 10 patients underwent trabeculectomy with subconjunctival mitomycin C (0.4mg/ml for 4 minutes) application combined with Ologen implantation subconjunctivally and subsclerally. Five of these patients underwent additional phacoemulsification with intraocular lens implantation. The Ologen implant was wet with 0.1 ml Bevacizumab. Result: All the eyes achieved target intraocular pressure (IOP), which was maintained until one year of follow-up. Two patients needed anterior chamber reformation at day two post surgery. One patient needed cataract surgery after four months of surgery and achieved target intraocular pressure on two topical antiglaucoma medicines. Conclusion: Vascular endothelial growth factor (VEGF) concentration has been seen to increase in the aqueous humor after filtration surgery. Ologen implantation helps in collagen remodelling, antifibroblastic response, and acts as a spacer. Bevacizumab augmented Ologen, in addition, targets the increased VEGF and helps in decreasing scarring. Anti-VEGF augmented Ologen in trabeculectomy with mitomycin C (MMC) hence appears to have encouraging short-term intraocular pressure control.

Keywords: ologen, anti-VEGF, trabeculectomy, scarring

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Authors: V. Hashim, P. N. Dileep

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Stent implantation is being seen as the most successful method to treat coronary artery diseases. Different types of stents are available in the market these days and the success of a stent implantation greatly depends on the proper selection of a suitable stent for a patient. Computer numerical simulation is the cost effective way to choose the compatible stent. Studies confirm that the design characteristics of stent do have great importance with regards to the pressure it can sustain, the maximum displacement it can produce, the developed stress concentration and so on. In this paper different designs of stent were analyzed together with balloon to optimize the stent and balloon system. Commercially available stent Palmaz-Schatz has been selected for analysis. Abaqus software is used to simulate the system. This work is the finite element analysis of the artery stent implant to find out the design factors affecting the stress and strain. The work consists of two phases. In the first phase, stress distribution of three models were compared - stent without balloon, stent with balloon of equal length and stent with balloon of extra length than stent. In second phase, three different design models of Palmaz-Schatz stent were compared by keeping the balloon length constant. The results obtained from analysis shows that, the design of the strut have strong effect on the stress distribution. A design with chamfered slots found better results. The length of the balloon also has influence on stress concentration of the stent. Increase in length of the balloon will reduce stress, but will increase dog boning effect.

Keywords: coronary stent, finite element analysis, restenosis, stress concentration

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Authors: Merve Colak, Gizem Donmez Yalcin

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Glutamate has many neurological functions in the central nervous system and is found at high concentrations in the brain. Increased levels of glutamate in the neuronal space are toxic, causing neuron damage and death. This is called glutamate-induced excitotoxicity. Excitotoxicity is among the causes of many neurological diseases such as trauma, cerebral ischemia, epilepsy, Parkinson's Disease, Alzheimer's Disease. Since neuroblastoma cells are known to be excitotoxic, we propose that excitotoxicity can be studied in neuroblastoma cells. Excitotoxicity can be induced using kainic acid in neuroblastoma cells. Measuring the secretion of glutamate, excitotoxicity can be analyzed in neuroblastoma cells.

Keywords: glutamate, excitotoxicity, kainic acid, Sirt4

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Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo N. Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

Abstract:

Background: While delays to care exist in resource rich settings, greater delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of traumatic brain injury (TBI) in Sub Saharan Africa (SSA). While many LMICs have government subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold. First, due to a lack of a functional CT scanner at the tertiary hospital, patients need to arrange their own transportation to the nearby private facility for CT scans. Second, self-financing for the private CT scans ranges from $80 - $130, which is near the average monthly income in Kampala. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified ‘three delays’ framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Maryam Risla Shahul Hameed, Tharsiga Yogarajah, Fritzy Mathew, Tayyaba Syed, Shalin Shaunak

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Aim: Auditing the adherence of Trauma and Orthopaedics Operative notes to the RCS Good Surgical Practice Guidelines. Method: Clinical audit conducted on 150 operative notes over a period of 2 months April- May 2023, including emergency and elective surgeries performed in Ashford and St. Peter’s Hospital. The RCS Good Practice Surgical Guidelines for an ideal operative note were used to compare.Results: Date of the procedure and signature of the surgeon were mentioned in all the notes by default in the electronic template being used. Title of the operation performed and whether elective or emergency were mentioned by 92% and 45%, respectively. Name of theatre anaesthetist and operating surgeons were mentioned by 73% and 93% respectively. Time of surgery mentioned by 26%. Operative findings and operative diagnosis mentioned by 83% and 53% respectively. Incision and complications of surgery mentioned in 80% and 53%, respectively. Details of tissue added/ altered/ removed mentioned by 46%. Information on prosthesis or implant used is mentioned by 54%. Details of closure and anticipated blood loss mentioned in 91% and 45% respectively. Antibiotic prophylaxis was mentioned by 63%, out of which only 23% mentioned the name and duration of the antibiotic. VTE prophylaxis was mentioned by 84%, out of which only 23% and 29% mentioned the name and duration of the prophylaxis, respectively. Conclusion: There is more for improvement in the operative notes for better continuity of care between the operating surgeons and other doctors in the wards taking care of the patients post operatively. We recommend to follow a standardized guidelines by all the nationwide and a standard template to be followed by all.

Keywords: surgery, notes, RCS, guidelines

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Authors: A. Razavykia, A. Esmaeilzadeh, S. Iranmanesh

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Many orthopedic implants like proximal humerus cases require lower surface roughness and almost immediate/short lead time surgery. Thus, rapid response from the manufacturer is very crucial. Tool path strategy of milling process has a direct influence on the surface roughness and lead time of medical implant. High-speed milling as promised process would improve the machined surface quality, but conventional or super-abrasive grinding still required which imposes some drawbacks such as additional costs and time. Currently, many CAD/CAM software offers some different tool path strategies to milling free form surfaces. Nevertheless, the users must identify how to choose the strategies according to cutting tool geometry, geometry complexity, and their effects on the machined surface. This study investigates the effect of different tool path strategies for milling a proximal humerus head during finishing operation on stainless steel 316L. Experiments have been performed using MAHO MH700 S vertical milling machine and four machining strategies, namely, spiral outward, spiral inward, and radial as well as zig-zag. In all cases, the obtained surfaces were analyzed in terms of roughness and dimension accuracy compared with those obtained by simulation. The findings provide evidence that surface roughness, dimensional accuracy, and machining time have been affected by the considered tool path strategy.

Keywords: CAD/CAM software, milling, orthopedic implants, tool path strategy

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