Search results for: bone marrow
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 802

Search results for: bone marrow

22 Selection and Preparation of High Performance, Natural and Cost-Effective Hydrogel as a Bio-Ink for 3D Bio-Printing and Organ on Chip Applications

Authors: Rawan Ashraf, Ahmed E. Gomaa, Gehan Safwat, Ayman Diab

Abstract:

Background: Three-dimensional (3D) bio-printing has become a versatile and powerful method for generating a variety of biological constructs, including bone or extracellular matrix scaffolds endo- or epithelial, muscle tissue, as well as organoids. Aim of the study: Fabricate a low cost DIY 3D bio-printer to produce 3D bio-printed products such as anti-microbial packaging or multi-organs on chips. We demonstrate the alignment between two types of 3D printer technology (3D Bio-printer and DLP) on Multi-organ-on-a-chip (multi-OoC) devices fabrication. Methods: First, Design and Fabrication of the Syringe Unit for Modification of an Off-the-Shelf 3D Printer, then Preparation of Hydrogel based on natural polymers Sodium Alginate and Gelatin, followed by acquisition of the cell suspension, then modeling the desired 3D structure. Preparation for 3D printing, then Cell-free and cell-laden hydrogels went through the printing process at room temperature under sterile conditions and finally post printing curing process and studying the printed structure regards physical and chemical characteristics. The hard scaffold of the Organ on chip devices was designed and fabricated using the DLP-3D printer, following similar approaches as the Microfluidics system fabrication. Results: The fabricated Bio-Ink was based onHydrogel polymer mix of sodium alginate and gelatin 15% to 0.5%, respectively. Later the 3D printing process was conducted using a higher percentage of alginate-based hydrogels because of it viscosity and the controllable crosslinking, unlike the thermal crosslinking of Gelatin. The hydrogels were colored to simulate the representation of two types of cells. The adaption of the hard scaffold, whether for the Microfluidics system or the hard-tissues, has been acquired by the DLP 3D printers with fabricated natural bioactive essential oils that contain antimicrobial activity, followed by printing in Situ three complex layers of soft-hydrogel as a cell-free Bio-Ink to simulate the real-life tissue engineering process. The final product was a proof of concept for a rapid 3D cell culturing approaches that uses an engineered hard scaffold along with soft-tissues, thus, several applications were offered as products of the current prototype, including the Organ-On-Chip as a successful integration between DLP and 3D bioprinter. Conclusion: Multiple designs for the organ-on-a-chip (multi-OoC) devices have been acquired in our study with main focus on the low cost fabrication of such technology and the potential to revolutionize human health research and development. We describe circumstances in which multi-organ models are useful after briefly examining the requirement for full multi-organ models with a systemic component. Following that, we took a look at the current multi-OoC platforms, such as integrated body-on-a-chip devices and modular techniques that use linked organ-specific modules.

Keywords: 3d bio-printer, hydrogel, multi-organ on chip, bio-inks

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21 Loss Quantification Archaeological Sites in Watershed Due to the Use and Occupation of Land

Authors: Elissandro Voigt Beier, Cristiano Poleto

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The main objective of the research is to assess the loss through the quantification of material culture (archaeological fragments) in rural areas, sites explored economically by machining on seasonal crops, and also permanent, in a hydrographic subsystem Camaquã River in the state of Rio Grande do Sul, Brazil. The study area consists of different micro basins and differs in area, ranging between 1,000 m² and 10,000 m², respectively the largest and the smallest, all with a large number of occurrences and outcrop locations of archaeological material and high density in intense farm environment. In the first stage of the research aimed to identify the dispersion of points of archaeological material through field survey through plot points by the Global Positioning System (GPS), within each river basin, was made use of concise bibliography on the topic in the region, helping theoretically in understanding the old landscaping with preferences of occupation for reasons of ancient historical people through the settlements relating to the practice observed in the field. The mapping was followed by the cartographic development in the region through the development of cartographic products of the land elevation, consequently were created cartographic products were to contribute to the understanding of the distribution of the absolute materials; the definition and scope of the material dispersed; and as a result of human activities the development of revolving letter by mechanization of in situ material, it was also necessary for the preparation of materials found density maps, linking natural environments conducive to ancient historical occupation with the current human occupation. The third stage of the project it is for the systematic collection of archaeological material without alteration or interference in the subsurface of the indigenous settlements, thus, the material was prepared and treated in the laboratory to remove soil excesses, cleaning through previous communication methodology, measurement and quantification. Approximately 15,000 were identified archaeological fragments belonging to different periods of ancient history of the region, all collected outside of its environmental and historical context and it also has quite changed and modified. The material was identified and cataloged considering features such as object weight, size, type of material (lithic, ceramic, bone, Historical porcelain and their true association with the ancient history) and it was disregarded its principles as individual lithology of the object and functionality same. As observed preliminary results, we can point out the change of materials by heavy mechanization and consequent soil disturbance processes, and these processes generate loading of archaeological materials. Therefore, as a next step will be sought, an estimate of potential losses through a mathematical model. It is expected by this process, to reach a reliable model of high accuracy which can be applied to an archeological site of lower density without encountering a significant error.

Keywords: degradation of heritage, quantification in archaeology, watershed, use and occupation of land

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20 Usage Of the Transpedicular Screw Fixation Method in the Treatment of Pediatric Patients with Injuries of the Thoracic and Lumbar Spine.

Authors: S. D. Zalepugin, A. E. Murzich, D. G. Satskevich, A. B. Palivanov

Abstract:

Introduction. The incidence of spinal injuries in patients under 18 years of age has increased significantly in recent years, which represents a significant economic, social and medical problem. The most common method of surgical stabilization of spinal fractures in pediatric patients is transpedicular posterior spinal fusion, which is widely used by spinal neurosurgeons in adult patients. Purpose of the study: This study evaluates the results of treatment of thoracolumbar spine lesions in children using the transpedicular screw fixation method. Materials and methods. From 2019 to 2024, 35 children with injuries to the thoracic and lumbar spine underwent surgical treatment using the transpedicular screw fixation method. Among the injured, girls prevailed (21 cases, 60%). The age of the victims ranged from 9 to 17 years. The main causes of damage were: catatrauma (19 cases), road accident (5 cases), sports injury (6 cases), and other reasons - 5 cases. In 5 cases, suicidal attempts occurred. Co-injury was observed in most cases (20 patients, or 57%), which is natural for high-energy injury. Vertebral-spinal injury with neurological disorders was observed in 13 patients, the disorders ranged from mild inferior (4 children) to moderate/severe paraparesis (5 patients) and inferior paraplegia (4 children). 6 children had pelvic organ dysfunction in the form of urinary and fecal retention or incontinence. All thirty-five patients, within a period of 1 to 57 days after the injury, underwent several surgical interventions from the posterior surgical access using a screw fixation method (posterior decompression + spinal fusion). In 12 cases, it was necessary to perform the second stage of surgical treatment - anterior decompression of the spinal cord or its roots. Verticalization of patients was carried out within 1 to 5 days after surgery. Results. In all patients, the nearest, up to 1 year, results were evaluated. In children operated in 2019-2021, the results were studied in terms of 3 to 5 years. The procedures used, clinical results and the quality of the fixative installation were assessed. All patients managed to achieve positive results. The use of internal fixation made it possible to carry out early verticalization of children, eliminate pain syndrome and achieve a regression of neurological disorders in most patients (especially in cases when the operation was performed early after injury - from 1 to 3 days). Within the first month, the ability to self-care was fully restored. Bone fusion was observed within 6-12 months after surgery. There were no complications after surgery. The analysis of postoperative radiographs, CT and MRI images revealed the correct standing of the screws in all cases. Conclusion. The posterior spinal fusion using the new method of screw fixation in pediatric patients allows to achieve durable stabilization of damage, begins early rehabilitation of patients and reduces the duration of hospital treatment by 2-3 times. Thus, we recommend the use of a transpedicular fixator in children as a reliable, technically feasible method for restoring spinal stability with a low risk of intra- and postoperative complications.

Keywords: pediatric patients, spinal injuries, transpedicular stabilization, operative treatment

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19 Supplementing Aerial-Roving Surveys with Autonomous Optical Cameras: A High Temporal Resolution Approach to Monitoring and Estimating Effort within a Recreational Salmon Fishery in British Columbia, Canada

Authors: Ben Morrow, Patrick O'Hara, Natalie Ban, Tunai Marques, Molly Fraser, Christopher Bone

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Relative to commercial fisheries, recreational fisheries are often poorly understood and pose various challenges for monitoring frameworks. In British Columbia (BC), Canada, Pacific salmon are heavily targeted by recreational fishers while also being a key source of nutrient flow and crucial prey for a variety of marine and terrestrial fauna, including endangered Southern Resident killer whales (Orcinus orca). Although commercial fisheries were historically responsible for the majority of salmon retention, recreational fishing now comprises both greater effort and retention. The current monitoring scheme for recreational salmon fisheries involves aerial-roving creel surveys. However, this method has been identified as costly and having low predictive power as it is often limited to sampling fragments of fluid and temporally dynamic fisheries. This study used imagery from two shore-based autonomous cameras in a highly active recreational fishery around Sooke, BC, and evaluated their efficacy in supplementing existing aerial-roving surveys for monitoring a recreational salmon fishery. This study involved continuous monitoring and high temporal resolution (over one million images analyzed in a single fishing season), using a deep learning-based vessel detection algorithm and a custom image annotation tool to efficiently thin datasets. This allowed for the quantification of peak-season effort from a busy harbour, species-specific retention estimates, high levels of detected fishing events at a nearby popular fishing location, as well as the proportion of the fishery management area represented by cameras. Then, this study demonstrated how it could substantially enhance the temporal resolution of a fishery through diel activity pattern analyses, scaled monthly to visualize clusters of activity. This work also highlighted considerable off-season fishing detection, currently unaccounted for in the existing monitoring framework. These results demonstrate several distinct applications of autonomous cameras for providing enhanced detail currently unavailable in the current monitoring framework, each of which has important considerations for the managerial allocation of resources. Further, the approach and methodology can benefit other studies that apply shore-based camera monitoring, supplement aerial-roving creel surveys to improve fine-scale temporal understanding, inform the optimal timing of creel surveys, and improve the predictive power of recreational stock assessments to preserve important and endangered fish species.

Keywords: cameras, monitoring, recreational fishing, stock assessment

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18 Assessment of Environmental Impact for Rice Mills in Burdwan District: Special Emphasis on Groundwater, Surface Water, Soil, Vegetation and Human Health

Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Rice milling is an important activity in agricultural economy of India, particularly the Burdwan district. However, the environmental impact of rice mills is frequently underestimated. The environmental impact of rice mills in the Burdwan district is a major source of concern, given the importance of rice milling in the local economy and food supply. In the Burdwan district, more than fifty (50) rice mills are in operation. The goal of this study is to investigate the effects of rice mills on several environmental components, with a particular emphasis on groundwater, surface water, soil, and vegetation. The research comprises a thorough review of numerous rice mills located around the district, utilising both qualitative and quantitative approaches. Water samples taken from wells near rice mills will be tested for groundwater quality, with an emphasis on factors such as heavy metal pollution and pollutant concentrations. Monitoring rice mill discharge into neighbouring bodies of water and studying the potential impact on aquatic ecosystems will be part of surface water evaluations. Furthermore, soil samples from the surrounding areas will be taken to examine changes in soil characteristics, nutrient content, and potential contamination from milling waste disposal. Vegetation studies will be conducted to investigate the effects of emissions and effluents on plant health and biodiversity in the region. The findings will provide light on the extent of environmental degradation caused by rice mills in the Burdwan district, as well as valuable insight into the effects of such operations on water, soil, and vegetation. The findings will aid in the development of appropriate legislation and regulations to reduce negative environmental repercussions and promote sustainable practises in the rice milling business. In some cases, heavy metals have been related to health problems. Heavy metals (As, Cd, Cu, Pb, Cr, Hg) are linked to skin, lung, brain, kidney, liver, metabolic, spleen, cardiovascular, haematological, immunological, gastrointestinal, testes, pancreatic, metabolic, and bone problems. As a result, this study contributes to a better knowledge of industrial environmental impacts and establishes the framework for future studies aimed at developing a more ecologically balanced and resilient Burdwan district. The following recommendations are offered for reducing the rice mill's environmental impact: To keep untreated effluents out of bodies of water, adequate waste management systems must be established. Use environmentally friendly rice milling processes to reduce pollution. To avoid soil pollution, rice mill by-products should be used as fertiliser in a controlled and appropriate manner. Groundwater, surface water, soil, and vegetation are all regularly monitored in order to study and adapt to environmental changes. By adhering to these principles, the rice milling industry of Burdwan district may achieve long-term growth while lowering its environmental effect and safeguarding the environment for future generations.

Keywords: groundwater, environmental analysis, biodiversity, rice mill, waste management, diseases, industrial impact

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17 Genetically Informed Precision Drug Repurposing for Rheumatoid Arthritis

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

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

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

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16 Statistical Models and Time Series Forecasting on Crime Data in Nepal

Authors: Dila Ram Bhandari

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Throughout the 20th century, new governments were created where identities such as ethnic, religious, linguistic, caste, communal, tribal, and others played a part in the development of constitutions and the legal system of victim and criminal justice. Acute issues with extremism, poverty, environmental degradation, cybercrimes, human rights violations, crime against, and victimization of both individuals and groups have recently plagued South Asian nations. Everyday massive number of crimes are steadfast, these frequent crimes have made the lives of common citizens restless. Crimes are one of the major threats to society and also for civilization. Crime is a bone of contention that can create a societal disturbance. The old-style crime solving practices are unable to live up to the requirement of existing crime situations. Crime analysis is one of the most important activities of the majority of intelligent and law enforcement organizations all over the world. The South Asia region lacks such a regional coordination mechanism, unlike central Asia of Asia Pacific regions, to facilitate criminal intelligence sharing and operational coordination related to organized crime, including illicit drug trafficking and money laundering. There have been numerous conversations in recent years about using data mining technology to combat crime and terrorism. The Data Detective program from Sentient as a software company, uses data mining techniques to support the police (Sentient, 2017). The goals of this internship are to test out several predictive model solutions and choose the most effective and promising one. First, extensive literature reviews on data mining, crime analysis, and crime data mining were conducted. Sentient offered a 7-year archive of crime statistics that were daily aggregated to produce a univariate dataset. Moreover, a daily incidence type aggregation was performed to produce a multivariate dataset. Each solution's forecast period lasted seven days. Statistical models and neural network models were the two main groups into which the experiments were split. For the crime data, neural networks fared better than statistical models. This study gives a general review of the applied statistics and neural network models. A detailed image of each model's performance on the available data and generalizability is provided by a comparative analysis of all the models on a comparable dataset. Obviously, the studies demonstrated that, in comparison to other models, Gated Recurrent Units (GRU) produced greater prediction. The crime records of 2005-2019 which was collected from Nepal Police headquarter and analysed by R programming. In conclusion, gated recurrent unit implementation could give benefit to police in predicting crime. Hence, time series analysis using GRU could be a prospective additional feature in Data Detective.

Keywords: time series analysis, forecasting, ARIMA, machine learning

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15 Prostheticly Oriented Approach for Determination of Fixture Position for Facial Prostheses Retention in Cases with Atypical and Combined Facial Defects

Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

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14 Development of PCL/Chitosan Core-Shell Electrospun Structures

Authors: Hilal T. Sasmazel, Seda Surucu

Abstract:

Skin tissue engineering is a promising field for the treatment of skin defects using scaffolds. This approach involves the use of living cells and biomaterials to restore, maintain, or regenerate tissues and organs in the body by providing; (i) larger surface area for cell attachment, (ii) proper porosity for cell colonization and cell to cell interaction, and (iii) 3-dimensionality at macroscopic scale. Recent studies on this area mainly focus on fabrication of scaffolds that can closely mimic the natural extracellular matrix (ECM) for creation of tissue specific niche-like environment at the subcellular scale. Scaffolds designed as ECM-like architectures incorporating into the host with minimal scarring/pain and facilitate angiogenesis. This study is related to combining of synthetic PCL and natural chitosan polymers to form 3D PCL/Chitosan core-shell structures for skin tissue engineering applications. Amongst the polymers used in tissue engineering, natural polymer chitosan and synthetic polymer poly(ε-caprolactone) (PCL) are widely preferred in the literature. Chitosan has been among researchers for a very long time because of its superior biocompatibility and structural resemblance to the glycosaminoglycan of bone tissue. However, the low mechanical flexibility and limited biodegradability properties reveals the necessity of using this polymer in a composite structure. On the other hand, PCL is a versatile polymer due to its low melting point (60°C), ease of processability, degradability with non-enzymatic processes (hydrolysis) and good mechanical properties. Nevertheless, there are also several disadvantages of PCL such as its hydrophobic structure, limited bio-interaction and susceptibility to bacterial biodegradation. Therefore, it became crucial to use both of these polymers together as a hybrid material in order to overcome the disadvantages of both polymers and combine advantages of those. The scaffolds here were fabricated by using electrospinning technique and the characterizations of the samples were done by contact angle (CA) measurements, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-Ray Photoelectron spectroscopy (XPS). Additionally, gas permeability test, mechanical test, thickness measurement and PBS absorption and shrinkage tests were performed for all type of scaffolds (PCL, chitosan and PCL/chitosan core-shell). By using ImageJ launcher software program (USA) from SEM photographs the average inter-fiber diameter values were calculated as 0.717±0.198 µm for PCL, 0.660±0.070 µm for chitosan and 0.412±0.339 µm for PCL/chitosan core-shell structures. Additionally, the average inter-fiber pore size values exhibited decrease of 66.91% and 61.90% for the PCL and chitosan structures respectively, compare to PCL/chitosan core-shell structures. TEM images proved that homogenous and continuous bead free core-shell fibers were obtained. XPS analysis of the PCL/chitosan core-shell structures exhibited the characteristic peaks of PCL and chitosan polymers. Measured average gas permeability value of produced PCL/chitosan core-shell structure was determined 2315±3.4 g.m-2.day-1. In the future, cell-material interactions of those developed PCL/chitosan core-shell structures will be carried out with L929 ATCC CCL-1 mouse fibroblast cell line. Standard MTT assay and microscopic imaging methods will be used for the investigation of the cell attachment, proliferation and growth capacities of the developed materials.

Keywords: chitosan, coaxial electrospinning, core-shell, PCL, tissue scaffold

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13 Combined Treatment with Microneedling and Chemical Peels Improves Periorbital Wrinkles and Skin Laxity

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

Abstract:

Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

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12 Emergency Department Utilisation of Older People Presenting to Four Emergency Departments

Authors: M. Fry, L. Fitzpatrick, Julie Considine, R. Z. Shaban, Kate Curtis

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Introduction: The vast majority of older Australians lives independently and are self-managing at home, despite a growing number living with a chronic illness that requires health intervention. Evidence shows that between 50% and 80% of people presenting to the emergency department (ED) are in pain. Australian EDs manage 7.2 million attendances every year and 1.4 million of these are people aged 65 years or more. Research shows that 28% of ED patients aged 65 years or more have Cognitive impairment (CI) associated with dementia, delirium and neurological conditions. Background: Traditional ED service delivery may not be suitable for older people who present with multiple, complex and ongoing illnesses. Likewise, ED clinical staff often perceive that their role should be focused more on immediate and potential lifethreatening illness and conditions which are episodic in nature. Therefore, the needs of older people and their family/carers may not be adequately addressed in the context of an ED presentation. Aim: We aimed to explore the utilisation and characteristics of older people presenting to four metropolitan EDs. Method: The findings being presented are part of a program of research exploring pain management practices for older persons with long bone fractures. The study was conducted across four metropolitan emergency departments of older patients (65years and over) and involved a 12-month randomised medical record audit (n=255). Results: ED presentations across four ED sites in 2012 numbered 168021, with 44778 (26.6%) patients aged 65 and over. Of the 44778 patients, the average age was 79.1 years (SD 8.54). There were more females 23932 (53.5%). The majority (26925: 85.0%) of older persons self-referred to the ED and lived independently. The majority arrived by ambulance (n=18553: 41.4%) and were allocated triage category was 3 (n=19,507:43.65%) or Triage category 4 at (n=15,389: 34.43%). The top five triage symptom presentations involved pain (n=8088; 18.25%), dyspnoea (n=4735; 10.7%), falls (n=4032; 9.1%), other (n=3984; 9.0%), cardiac (n=2987; 6.7%). The top five system based diagnostic presentations involved musculoskeletal (n=8902; 20.1%), cardiac (n=6704:15.0%), respiratory (n=4933; 11.0%), neurological (n=4909; 11.0%), gastroenterology (n=4321; 9.7%). On review of one tertiary hospital database the vital signs on average at time triage: Systolic Blood Pressure 143.6mmHg. Heart Rate 83.4 beats/minute; Respiratory Rate 18.5 breaths/ minute; Oxygen saturation 97.0% and Tympanic temperature 36.7 and Blood Glucose Level 7.4mmols/litre. The majority presented with a Glasgow Coma Score of 14 or higher. On average the older person stayed in the ED 4:56 (SD 3:28minutes).The average time to be seen was 39 minutes (SD 48 minutes). The majority of older persons were admitted (n=27562: 61.5%), did not wait for treatment (n= 8879: 0.02%) discharged home (n=16256: 36.0%). Conclusion: The vast majority of older persons are living independently, although many require admission on arrival to the ED. Many arrived in pain and with musculoskeletal injuries and or conditions. New models of care need to be considered, which may better support self-management and independent living of the older person and the National Emergency Access Targets.

Keywords: chronic, older person, aged care, emergency department

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11 The Use of STIMULAN Resorbable Antibiotic Beads in Conjunction with Autologous Tissue Transfer to Treat Recalcitrant Infections and Osteomyelitis in Diabetic Foot Wounds

Authors: Hayden R Schott, John M Felder III

Abstract:

Introduction: Chronic lower extremity wounds in the diabetic and vasculopathic populations are associated with a high degree of morbidity.When wounds require more extensive treatment than can be offered by wound care centers, more aggressive solutions involve local tissue transfer and microsurgical free tissue transfer for achieving definitive soft tissue coverage. These procedures of autologous tissue transfer (ATT) offer resilient, soft tissue coverage of limb-threatening wounds and confer promising limb salvage rates. However, chronic osteomyelitis and recalcitrant soft tissue infections are common in severe diabetic foot wounds and serve to significantly complicate ATT procedures. Stimulan is a resorbable calcium sulfate antibiotic carrier. The use of stimulan antibiotic beads to treat chronic osteomyelitis is well established in the orthopedic and plastic surgery literature. In these procedures, the beads are placed beneath the skin flap to directly deliver antibiotics to the infection site. The purpose of this study was to quantify the success of Stimulan antibiotic beads in treating recalcitrant infections in patients with diabetic foot wounds receiving ATT. Methods: A retrospective review of clinical and demographic information was performed on patients who underwent ATT with the placement of Stimulan antibiotic beads for attempted limb salvage from 2018-21. Patients were analyzed for preoperative wound characteristics, demographics, infection recurrence, and adverse outcomes as a result of product use. The primary endpoint was 90 day infection recurrence, with secondary endpoints including 90 day complications. Outcomes were compared using basic statistics and Fisher’s exact tests. Results: In this time span, 14 patients were identified. At the time of surgery, all patients exhibited clinical signs of active infection, including positive cultures and erythema. 57% of patients (n=8) exhibited chronic osteomyelitis prior to surgery, and 71% (n=10) had exposed bone at the wound base. In 57% of patients (n=8), Stimulan beads were placed beneath a free tissue flap and beneath a pedicle tissue flap in 42% of patients (n=6). In all patients, Stimulan beads were only applied once. Recurrent infections were observed in 28% of patients (n=4) at 90 days post-op, and flap nonadherence was observed in 7% (n=1). These were the only Stimulan related complications observed. Ultimately, lower limb salvage was successful in 85% of patients (n=12). Notably, there was no significant association between the preoperative presence of osteomyelitis and recurrent infections. Conclusions: The use of Stimulanantiobiotic beads to treat recalcitrant infections in patients receiving definitive skin coverage of diabetic foot wounds does not appear to demonstrate unnecessary risk. Furthermore, the lack of significance between the preoperative presence of osteomyelitis and recurrent infections indicates the successful use of Stimulan to dampen infection in patients with osteomyelitis, as is consistent with the literature. Further research is needed to identify Stimulan as the significant contributor to infection treatment using future cohort and case control studies with more patients. Nonetheless, the use of Stimulan antibiotic beads in patients with diabetic foot wounds demonstrates successful infection suppression and maintenance of definitive soft tissue coverage.

Keywords: wound care, stimulan antibiotic beads, free tissue transfer, plastic surgery, wound, infection

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

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

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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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9 CT Images Based Dense Facial Soft Tissue Thickness Measurement by Open-source Tools in Chinese Population

Authors: Ye Xue, Zhenhua Deng

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Objectives: Facial soft tissue thickness (FSTT) data could be obtained from CT scans by measuring the face-to-skull distances at sparsely distributed anatomical landmarks by manually located on face and skull. However, automated measurement using 3D facial and skull models by dense points using open-source software has become a viable option due to the development of computed assisted imaging technologies. By utilizing dense FSTT information, it becomes feasible to generate plausible automated facial approximations. Therefore, establishing a comprehensive and detailed, densely calculated FSTT database is crucial in enhancing the accuracy of facial approximation. Materials and methods: This study utilized head CT scans from 250 Chinese adults of Han ethnicity, with 170 participants originally born and residing in northern China and 80 participants in southern China. The age of the participants ranged from 14 to 82 years, and all samples were divided into five non-overlapping age groups. Additionally, samples were also divided into three categories based on BMI information. The 3D Slicer software was utilized to segment bone and soft tissue based on different Hounsfield Unit (HU) thresholds, and surface models of the face and skull were reconstructed for all samples from CT data. Following procedures were performed unsing MeshLab, including converting the face models into hollowed cropped surface models amd automatically measuring the Hausdorff Distance (referred to as FSTT) between the skull and face models. Hausdorff point clouds were colorized based on depth value and exported as PLY files. A histogram of the depth distributions could be view and subdivided into smaller increments. All PLY files were visualized of Hausdorff distance value of each vertex. Basic descriptive statistics (i.e., mean, maximum, minimum and standard deviation etc.) and distribution of FSTT were analysis considering the sex, age, BMI and birthplace. Statistical methods employed included Multiple Regression Analysis, ANOVA, principal component analysis (PCA). Results: The distribution of FSTT is mainly influenced by BMI and sex, as further supported by the results of the PCA analysis. Additionally, FSTT values exceeding 30mm were found to be more sensitive to sex. Birthplace-related differences were observed in regions such as the forehead, orbital, mandibular, and zygoma. Specifically, there are distribution variances in the depth range of 20-30mm, particularly in the mandibular region. Northern males exhibit thinner FSTT in the frontal region of the forehead compared to southern males, while females shows fewer distribution differences between the northern and southern, except for the zygoma region. The observed distribution variance in the orbital region could be attributed to differences in orbital size and shape. Discussion: This study provides a database of Chinese individuals distribution of FSTT and suggested opening source tool shows fine function for FSTT measurement. By incorporating birthplace as an influential factor in the distribution of FSTT, a greater level of detail can be achieved in facial approximation.

Keywords: forensic anthropology, forensic imaging, cranial facial reconstruction, facial soft tissue thickness, CT, open-source tool

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8 A Case Study of a Rehabilitated Child by Joint Efforts of Parents and Community

Authors: Fouzia Arif, Arif S. Mohammad, Hifsa Altaf, Lubna Raees

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Introduction: The term "disability", refers to any condition that impedes the completion of daily tasks using traditional methods. In developing countries like Pakistan, disable population is usually excluded from the mainstream. In squatter settlements the situation is more critical. Sultanabad is one of the squatter settlements of Karachi. Purpose of case study is to improve the health of disabled children’s, and create awareness among the parents and community. Through a household visit, Shiraz, a young disabled boy of 15.5 years old was identified. Her mother articulated that her son was living normally and happily with his parents two years back. When he was 13 years old and student of class 8th, both his legs were traumatized in a Railway Train Accident while playing cricket. He got both femoral shaft fractured severely. He was taken to Jinnah Post Graduate Medical Centre (JPMC) where his left leg was amputated at above knee level and right leg was opened & fixed by reduction internally, luckily bone healed moderately with the passage of time. Methods: In Squatter settlements of Karachi Sultanabad, a survey was conducted in two sectors. Disability screening questionnaire was developed, collaboration with community through household visits, outreach sessions 23cases of disabled were identified who were socialized through sports, Musical program and get-together was organized with stockholder for creating awareness among community and parent’s. Collaboration was established with different NGOs, Government, stakeholders and community support for establishment of Physiotherapy Center. During home visit it was identified that Shiraz was on bed since last 1 year, his family could not afforded cost of physiotherapist and medical consultation due to poverty. Parents counseling was done mentioning that Shiraz needed to take treatment. After motivation his parents agreed for treatment. He was consulted by an orthopedic surgeon in AKUH, Who referred to DMC University of Health Science for rehabilitation service. There he was assessed and referred for Community Based Physiotherapy Centre Sultanabad. Physiotherapist visited home along with Coordinator for Special children and assessed him regularly, planned Physiotherapy treatment for abdominal, high muscles strutting exercise foot muscles strengthening exercise, knee mobilization weight bearing from partial to full weight gradually, also strengthen exercise were given for residual limb as the boy was dependent on it. He was also provided by an artificial leg and training was done. Result: Shiraz is now fully mobile, he can walk independently even out of home, functional ability progress improved and dependency factors reduced. It was difficult but not impossible. We all have sympathy but if we have empathy then we can rehabilitate the community in a better way. His parents are very happy and also the community is surprised to see him in such better condition. Conclusion: Combined efforts of physiotherapist, Coordinator of special children, community and parents made a drastic change in Shiraz’s case by continuously motivating him for better outcome. He is going to school regularly without support. Since he belongs to a poor family he faces financial constraints for education and clinical follow ups regularly.

Keywords: femoral shaft fracture, trauma, orthopedic surgeon, physiotherapy treatment

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7 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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6 Green Architecture from the Thawing Arctic: Reconstructing Traditions for Future Resilience

Authors: Nancy Mackin

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Historically, architects from Aalto to Gaudi to Wright have looked to the architectural knowledge of long-resident peoples for forms and structural principles specifically adapted to the regional climate, geology, materials availability, and culture. In this research, structures traditionally built by Inuit peoples in a remote region of the Canadian high Arctic provides a folio of architectural ideas that are increasingly relevant during these times of escalating carbon emissions and climate change. ‘Green architecture from the Thawing Arctic’ researches, draws, models, and reconstructs traditional buildings of Inuit (Eskimo) peoples in three remote, often inaccessible Arctic communities. Structures verified in pre-contact oral history and early written history are first recorded in architectural drawings, then modeled and, with the participation of Inuit young people, local scientists, and Elders, reconstructed as emergency shelters. Three full-sized building types are constructed: a driftwood and turf-clad A-frame (spring/summer); a stone/bone/turf house with inwardly spiraling walls and a fan-shaped floor plan (autumn); and a parabolic/catenary arch-shaped dome from willow, turf, and skins (autumn/winter). Each reconstruction is filmed and featured in a short video. Communities found that the reconstructed buildings and the method of involving young people and Elders in the reconstructions have on-going usefulness, as follows: 1) The reconstructions provide emergency shelters, particularly needed as climate change worsens storms, floods, and freeze-thaw cycles and scientists and food harvesters who must work out of the land become stranded more frequently; 2) People from the communities re-learned from their Elders how to use materials from close at hand to construct impromptu shelters; 3) Forms from tradition, such as windbreaks at entrances and using levels to trap warmth within winter buildings, can be adapted and used in modern community buildings and housing; and 4) The project initiates much-needed educational and employment opportunities in the applied sciences (engineering and architecture), construction, and climate change monitoring, all offered in a culturally-responsive way. Elders, architects, scientists, and young people added innovations to the traditions as they worked, thereby suggesting new sustainable, culturally-meaningful building forms and materials combinations that can be used for modern buildings. Adding to the growing interest in bio-mimicry, participants looked at properties of Arctic and subarctic materials such as moss (insulation), shrub bark (waterproofing), and willow withes (parabolic and catenary arched forms). ‘Green Architecture from the Thawing Arctic’ demonstrates the effective, useful architectural oeuvre of a resilient northern people. The research parallels efforts elsewhere in the world to revitalize long-resident peoples’ architectural knowledge, in the interests of designing sustainable buildings that reflect culture, heritage, and identity.

Keywords: architectural culture and identity, climate change, forms from nature, Inuit architecture, locally sourced biodegradable materials, traditional architectural knowledge, traditional Inuit knowledge

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5 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning

Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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4 Implementation of Autologous Adipose Graft from the Abdomen for Complete Fat Pad Loss of the Heel Following a Traumatic Open Fracture Secondary to a Motor Vehicle Accident: A Case Study

Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

Abstract:

Introduction: This study explores the potential applications of autologous pedal fat pad grafting as a minimally invasive therapeutic strategy for addressing pedal fat pad loss. Without adequate shock absorbing tissue, a patient can experience functional deficits, ulcerations, loss of quality of life, and significant limitations with ambulation. This study details a novel technique involving autologous adipose grafting from the abdomen to enhance plantar fat pad thickness in a patient involved in a severe motor vehicle accident which resulted in total fat pad loss of the heel. Autologous adipose grafting (AAG) was used following adipose allografting in an effort to recreate a normal shock absorbing surface to allow return to activities of daily living and painless ambulation. Methods: A 46-year-old male sustained multiple open pedal fractures and necrosis to the heel fat pad after a motorcycle accident, which resulted in complete loss of the calcaneal fat pad. The patient underwent serial debridement’s, utilization of wound vac therapy and split thickness skin grafting to accomplish complete closure, despite complete loss of adipose to area. Patient presented with complaints of pain on ambulation, inability to bear weight on the heel, recurrent ulcerations, admitted had not been ambulating for two years. Clinical exam demonstrated complete loss of the plantar fat pad with a thin layer of epithelial tissue overlying the calcaneal bone, allowing visibility of the osseous contour of the calcaneus. Scar tissue had formed in place of the fat pad, with thickened epithelial tissue extending from the midfoot to the calcaneus. After conservative measures were exhausted, the patient opted for initial management by adipose allograft matrix (AAM) injections. Post operative X-ray imaging revealed noticeable improvement in calcaneal fat pad thickness. At 1 year follow up, the patient was able to ambulate without assistive devices. The fat pad at this point was significantly thicker than it was pre-operatively, but the thickness did not restore to pre-accident thickness. In order to compare the take of allograft versus autografting of adipose tissue, the decision to use adipose autograft through abdominal liposuction harvesting was deemed suitable. A general surgeon completed harvesting of adipose cells from the patient’s abdomen via liposuction, and a podiatric surgeon performed the AAG injection into the heel. Total of 15 cc’s of autologous adipose tissue injected to the calcaneus. Results: There was a visual increase in the calcaneal fat pad thickness both clinically and radiographically. At the 6-week follow up, imaging revealed retention of the calcaneal fat pad thickness. Three months postop, patient returned to activities of daily living and increased quality of life due to their increased ability to ambulate. Discussion: AAG is a novel treatment for pedal fat pad loss. These treatments may be viable and reproducible therapeutic choices for patients suffering from fat pad atrophy, fat pad loss, and/or plantar ulcerations. Both treatments of AAM and AAG exhibited similar therapeutic results by providing pain relief for ambulation and allowing for patients to return to their quality of life.

Keywords: podiatry, wound, adipose, allograft, autograft, wound care, limb reconstruction, injection, limb salvage

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3 Amniotic Fluid Mesenchymal Stem Cells Selected for Neural Specificity Ameliorates Chemotherapy Induced Hearing Loss and Pain Perception

Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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2 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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1 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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