Search results for: mice bone
180 Pyrazolylpyrazolines: Design, Synthesis and Biological Evaluation as Dual Acting Antimalarial-Antileishmanial Agents
Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit
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Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase
Procedia PDF Downloads 341179 Implementation of Enterprise Asset Management (E-AM) System at Oman Electricity Transmission Company
Authors: Omran Al Balushi, Haitham Al Rawahi
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Enterprise Asset Management (eAM) has been implemented across different Generation, Transmission and Distribution subsidiaries in Nama Group companies. As part of Nama group, Oman Electricity Transmission Company (OETC) was the first company to implement this system. It was very important for OETC to implement and maintain such a system to achieve its business objectives and for effective operations, which will also support the delivery of the asset management strategy. Enterprise Asset Management (eAM) addresses the comprehensive asset maintenance requirements of Oman Electricity Transmission Company (OETC). OETC needs to optimize capacity and increase utilization, while lowering unit production. E-AM will enable OETC to adopt this strategy. Implementation of e-AM has improved operation performance with preventive and scheduled maintenance as well as it increased safety. Implementation of e-AM will also enable OETC to create optimal asset management strategy which will increase revenue and decrease cost by effectively monitoring operational data such as maintenance history and operation conditions. CMMS (Computerised Maintenance Management System) is the main software and the back-bone of e-AM system. It is used to provide an improved working practice to properly establish information and data flow related to maintenance activities. Implementation of e-AM system was one of the factors that supported OETC to achieve ISO55001 Certificate on fourth quarter of 2016. Also, full implementation of e-AM system will result in strong integration between CMMS and Geographical Information Systems (GIS) application and it will improve OETC to build a reliable maintenance strategy for all asset classes in its Transmission network. In this paper we will share our experience and knowledge of implementing such a system and how it supported OETC’s management to make decisions. Also we would highlight the challenges and difficulties that we encountered during the implementation of e-AM. Also, we will list some features and advantages of e-AM in asset management, preventive maintenance and maintenance cost management.Keywords: CMMS, Maintenance Management, Asset Management, Maintenance Strategy
Procedia PDF Downloads 144178 Service Evaluation of Consent for Hand and Wrist Surgery and Formulation of Evidence-Based Guidelines
Authors: Parsa Keyvani, Alistair Phillips, David Warwick
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Background: The current process for gaining patient consent for hand and wrist surgery at University Hospital Southampton (UHS) is paper-based and makes use of generic forms provided by the NHS and no patient information leaflet is available relating to hand and wrist surgery. Aims: To evaluate the process of obtaining clinical consent and suggest ways in which the service can be improved. Methods: A log-book review of four orthopaedic surgeons at UHS was carried out over a three-month period in order to identify the 10 most common types of elective hand and wrist surgeries performed. A literature review was carried out to identify the complications of these surgeries. The surgeries were then divided into 6 types: nerve, bone, ligament, joint, tendon and dupuytren’s surgery. A digitised consent form was created covering the complications of all 6 surgery types. Finally, the surgeons at the orthopaedic department of UHS were asked whether they prefer the old paper-based or the digitised consent form. Results: All of the surgeons felt that the procedure type-based form was easier to read, use and understand. Conclusion: This research highlights a number of problems related to the use of current NHS consent forms. The proposed solution is to use a set of digitised, procedure type-based consent forms. Digital consent forms can be filled in in advance and sent to the patient electronically along with any relevant information leaflets, thus giving them time to absorb the information and come up with any questions before they have their pre-procedure discussion with their doctor. This would allow the doctor to focus the consultation on the patient rather than writing out the consent form and would ultimately be a step forward in making the NHS a global digital leader and fully embrace the opportunity offered by technology.Keywords: digitised consent form, elective surgery, hand surgery complications, informed consent, procedure type-based consent form
Procedia PDF Downloads 86177 The Importance of a Coating and Architecture of the Surface Metal on the Survival of Uncemented Total Knee Arthroplasty
Authors: Raymond Puijk, Rachid Rassir, Inger N. Sierevelt, Anneke Spekenbrink-Sporen, Bart G. C. W. Pijls, Rob G. H. H. Nelissen, Peter A. Nolte
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Background: Among uncemented total knee arthroplasty (TKA), a wide variety of metal surface structures (MSS) and coatings exist to enhance implants' biological properties (i.e., bone ingrowth). This study explores the variety of MSS-coating combinations and compares their mid-long-term survivorships with cemented TKAs, by using data from the Dutch Arthroplasty Register. Methods: A total of 235,500 cemented and 11,132 uncemented primary TKAs with a median follow-up of 5.1 years were included. MSS-coating combinations were (1) Porous-uncoated (n=8986), (2) Beaded-hydroxyapatite (HA)(n=1093), (3) Matte-uncoated (n=846), (4) Matte-Titanium-nitride (TiN) (n=207). Five- and 10-year revision-free survival for all-cause revisions, and aseptic loosening of the tibial component, were calculated and compared by using Kaplan-Meier, Log-rank tests, and multivariable Cox proportional hazard regression analyses. Results: Ten-year survival rates with all-cause revisions as an endpoint, were 94.2% for cement, and 94.7%, 96.3%, 92.1%, and 79.0% for porous-uncoated, beaded-HA, matte-uncoated, and Matte-TiN, respectively (p<0.01). Rates for aseptic loosening were 98.8% for cemented, and 98.7%, 99.8%, 97.2%, and 94.9% for the uncemented, respectively (p<0.01).The beaded-HA implants were half the risk for an all-cause revision compared to cemented implants (p<0.01). Matte-uncoated and matte-TiN implants were at more risk of an all-cause revision than cemented implants (p=0.01, p<0.01). Proportions of revisions for aseptic loosening were comparable among most groups. Conclusion: Based on Dutch registry data, four main MSS-coating combinations among uncemented TKAs were found. survivorships for all-cause revisions and aseptic release differed widely between groups. Beaded-HA and porous-uncoated implants had the best survival rates among the uncemented TKAs and were non-inferior to the cemented TKAs.Keywords: total knee arthroplasty, cement, uncemented, cementless;, metal surface structure, coating
Procedia PDF Downloads 152176 Various Body Measurements of Hair, Boer x Hair F1 Crossbred Kids and Effects of Some Environmental Factors on These Traits
Authors: M. Bolacalı, Y. Öztürk, O. Yılmaz, M. Küçük, M. A. Karslı
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The aim of the study was to determine various body measurements from the birth to the 30-day age of Boer x Hair goats F1 crossbred kids and pure Hair goat kids raised in Van in Eastern Anatolia region, and reveal factors such as the effects of year, dame body weight, genotype, dame age, birth type and sex on this parameter. 49 kids born in 2012 and 76 kids born in 2014 were utilized in the study. In the statistical analysis of various body measurements data was performed using the General Lineer Model procedure in SPSS software. Duncan's multiple range test was used for multiple comparisons. Boer x Hair goats F1 crossbred kids and pure Hair goat kids from various body measurements cidago height, body length, chest length, chest depth, chest circumference, circumference of leg, cannon bone circumference, chest width were determinated in general respectively 29.90 and 27.88 cm; 29.49 and 27.93 cm; 17.28 and 16.68 cm; 13.34 and 12.82 cm; 31.74 and 29.85 cm; 28.43 and 23.95 cm; 5.41 and 5.15 cm; 8.71 and 7.63 cm at birth, respectively; 35.01 and 32.98 cm; 35.20 and 33.30 cm; 18.82 and 18.17 cm; 15.64 and 14.83 cm; 39.08 and 37.30 cm; 34.29 and 29.25 cm; 5.80 and 5.42 cm; 9.87 and 8.85 cm at 30 days age, respectively. Among factors affecting cidago height in this study, the effect of dame body weight and sex were not significant, but genotype, dame age and birth type were significant (P < 0,05 and P < 0,01) at birth; dame body weight effect of the cidago height was not significant, but the effect of genotype, birth type, of dame age and sex were significant (P < 0.05, P < 0.05 and P<0.001) at 30-day age. The effect of genotype and sex of body length were not significant, but dam age, dame body weight and birth type were significant (P < 0.05, P < 0.05 and P<0.001, respectively) at birth; the effect of sex to body length was not significant, but genotype, dame age, dame body weight and birth type were significant (P < 0.01, P < 0.05, P < 0.05 and P < 0.001, respectively) at 30-day age. While circumference of leg was insignificant the effect of dame age and sex, genotype, dame body weight and type of the birth were significant (P < 0.001, P < 0.05 and P < 0.001) at birth; the circumstance of leg at 30-day age was found to be important the effect of examined other factors except for sex (P < 0.05 and P < 0.001). The obtained results, when considered in terms of a variety of body sizes, from birth to 30-day age growth period, showed that the kids of Boer x Hair Goat F1 hybrids have higher values than the kids of Hair Goats.Keywords: Boer x hair goat F1 crossbred, hair goat, body measurements, cidago height
Procedia PDF Downloads 349175 Polycystic Ovarian Syndrome (PCOS) as an Evolutionary Mismatch Disorder: An Argument for the Significance of Hyperandrogenism on Reproductive Fitness in Ancestral Populations
Authors: Courtney Manthey-Pierce, Anna Warrener
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Polycystic ovarian syndrome (PCOS) is the most common endocrine disruptive disorder in females. PCOS is primarily characterized by polycystic ovaries, anovulation, hirsutism, insulin resistance, and hyperandrogenism. Despite negative reproductive consequences for females from anovulation and endocrine dysfunction, genes associated with the pathogenesis of PCOS are highly hereditable (h2 = 0.72). An evolutionary mismatch occurs when a trait that evolved in one environment has become maladaptive in another environment. The idea that PCOS is an evolutionary mismatch disease has been promoted by several researchers. Each trait of the resulting PCOS phenotype should be investigated individually in order to demonstrate an evolutionary mismatch. Hyperandrogenism is often regarded as the main characteristic of PCOS Hyperandrogenism may have aided with conception in older females, increased bone mineral density, and supported prolonged breastfeeding in nutritionally distressed populations. Because of the high prevalence of PCOS in the modern world, approximately 6%, it is often argued that PCOS emerged in an ancestral population prior to the migration out of Africa approximately 200,000 years ago. This environment would be characterized by sporadic periods of nutrition deficit and resource hardships as the climate began changing. Presently, modern society is characterized by obesity and sedentary lifestyles. The prevalence of obesity renders hyperandrogenism PCOS useless as there are no periods of nutritional distress requiring androgens for increased reproductive rates. In an ancestral environment, hyperandrogenism would likely lead to sporadic anovulation and mild secondary symptoms, however high levels of androgens in a modern environment led to prolonged if not permanent infertility and excessive secondary problems. Thus, hyperandrogenism related to PCOS appears to meet evolutionary mismatch criteria. Seen in this light, PCOS may be effectively treated as a probably evolutionary mismatch.Keywords: evolutionary mismatch, heritability, hyperandrogenism, mismatch disorder
Procedia PDF Downloads 247174 Traumatic Chiasmal Syndrome Following Traumatic Brain Injury
Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao
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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.
Procedia PDF Downloads 79173 The Reasons for Vegetarianism in Estonia and its Effects to Body Composition
Authors: Ülle Parm, Kata Pedamäe, Jaak Jürimäe, Evelin Lätt, Aivar Orav, Anna-Liisa Tamm
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Vegetarianism has gained popularity across the world. It`s being chosen for multiple reasons, but among Estonians, these have remained unknown. Previously, attention to bone health and probable nutrient deficiency of vegetarians has been paid and in vegetarians lower body mass index (BMI) and blood cholesterol level has been found but the results are inconclusive. The goal was to explain reasons for choosing vegetarian diet in Estonia and impact of vegetarianism to body composition – BMI, fat percentage (fat%), fat mass (FM), and fat free mass (FFM). The study group comprised of 68 vegetarians and 103 omnivorous. The determining body composition with DXA (Hologic) was concluded in 2013. Body mass (medical electronic scale, A&D Instruments, Abingdon, UK) and height (Martin metal anthropometer to the nearest 0.1 cm) were measured and BMI calculated (kg/m2). General data (physical activity level included) was collected with questionnaires. The main reasons why vegetarianism was chosen were the healthiness of the vegetarian diet (59%) and the wish to fight for animal rights (72%) Food additives were consumed by less than half of vegetarians, more often by men. Vegetarians had lower BMI than omnivores, especially amongst men. Based on BMI classification, vegetarians were less obese than omnivores. However, there were no differences in the FM, FFM and fat percentage figures of the two groups. Higher BMI might be the cause of higher physical activity level among omnivores compared with vegetarians. For classifying people as underweight, normal weight, overweight and obese both BMI and fat% criteria were used. By BMI classification in comparison with fat%, more people in the normal weight group were considered; by using fat% in comparison with BMI classification, however, more people categorized as overweight. It can be concluded that the main reasons for vegetarianism chosen in Estonia are healthiness of the vegetarian diet and the wish to fight for animal rights and vegetarian diet has no effect on body fat percentage, FM and FFM.Keywords: body composition, body fat percentage, body mass index, vegetarianism
Procedia PDF Downloads 416172 Noncovalent Antibody-Nanomaterial Conjugates: A Simple Approach to Produce Targeted Nanomedicines
Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht
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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.Keywords: bioengineering, cancer, nanomedicine, polymer chemistry
Procedia PDF Downloads 141171 Tracking of Intramuscular Stem Cells by Magnetic Resonance Diffusion Weighted Imaging
Authors: Balakrishna Shetty
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Introduction: Stem Cell Imaging is a challenging field since the advent of Stem Cell treatment in humans. Series of research on tagging and tracking the stem cells has not been very effective. The present study is an effort by the authors to track the stem cells injected into calf muscles by Magnetic Resonance Diffusion Weighted Imaging. Materials and methods: Stem Cell injection deep into the calf muscles of patients with peripheral vascular disease is one of the recent treatment modalities followed in our institution. 5 patients who underwent deep intramuscular injection of stem cells as treatment were included for this study. Pre and two hours Post injection MRI of bilateral calf regions was done using 1.5 T Philips Achieva, 16 channel system using 16 channel torso coils. Axial STIR, Axial Diffusion weighted images with b=0 and b=1000 values with back ground suppression (DWIBS sequence of Philips MR Imaging Systems) were obtained at 5 mm interval covering the entire calf. The invert images were obtained for better visualization. 120ml of autologous bone marrow derived stem cells were processed and enriched under c-GMP conditions and reduced to 40ml solution containing mixture of above stem cells. Approximately 40 to 50 injections, each containing 0.75ml of processed stem cells, was injected with marked grids over the calf region. Around 40 injections, each of 1ml normal saline, is injected into contralateral leg as control. Results: Significant Diffusion hyper intensity is noted at the site of injected stem cells. No hyper intensity noted before the injection and also in the control side where saline was injected conclusion: This is one of the earliest studies in literature showing diffusion hyper intensity in intramuscularly injected stem cells. The advantages and deficiencies in this study will be discussed during the presentation.Keywords: stem cells, imaging, DWI, peripheral vascular disease
Procedia PDF Downloads 74170 Formulation, Nutritive Value Assessment And Effect On Weight Gain Of Infant Formulae Prepared From Locally Available Materia
Authors: J. T. Johnson, R. A. Atule, E. Gbodo
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The widespread problem of infant malnutrition in developing countries has stirred efforts in research, development and extension by both local and international organizations. As a result, the formulation and development of nutritious weaning foods from local and readily available raw materials which are cost effective has become imperative in many developing countries. Thus, local and readily available raw materials where used to compound and develop nutritious new infant formulae. The materials used for this study include maize, millet, cowpea, pumpkin, fingerlings, and fish bone. The materials where dried and blended to powder. The powders were weighed in the ratio of 4:4:4:3:1:1 respectively and were then mixed properly. Analysis of nutritive value was conducted on the formulae and compared with NAN-2 standard and results reveals that the formulae had reasonable amount of moisture, lipids, carbohydrate, protein, and fibre. Although NAN-2 was superior in both carbohydrate and protein, the new infant formula was higher in mineral elements, vitamins, fibre, and lipids. All the essentials vitamins and both macro and micro minerals where found in appreciable quantity capable of meeting the biochemical and physiological demand of the body while the anti-nutrients composition were significantly below FAO and WHO safe limits. Finally, the compounded infant formulae was feed to a set of albino Wistar rats while some other set of rats was feed with NAN-2 for the period of twenty seven (27) days and body weight was measure at three days intervals. The results of body weight changes was spectacular as their body weight over shot or almost double that of those animals that were feed with NAN-2 at each point of measurement. The results suggest that the widespread problem of infant malnutrition in the developing world especially among the low income segment of the society can now be reduced if not totally eradicated since nutritive and cost effective weaning formulae can be prepared locally from common readily available materials.Keywords: formulation, nutritive value, local, materials
Procedia PDF Downloads 378169 Hyper-Immunoglobulin E (Hyper-Ige) Syndrome In Skin Of Color: A Retrospective Single-Centre Observational Study
Authors: Rohit Kothari, Muneer Mohamed, Vivekanandh K., Sunmeet Sandhu, Preema Sinha, Anuj Bhatnagar
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Introduction: Hyper-IgE syndrome is a rare primary immunodeficiency syndrome characterised by triad of severe atopic dermatitis, recurrent pulmonary infections, and recurrent staphylococcal skin infections. The diagnosis requires a high degree of suspicion, typical clinical features, and not mere rise in serum-IgE levels, which may be seen in multiple conditions. Genetic studies are not always possible in a resource poor setting. This study highlights various presentations of Hyper-IgE syndrome in skin of color children. Case-series: Our study had six children of Hyper-IgE syndrome aged twomonths to tenyears. All had onset in first ten months of life except one with a late-onset at two years. All had recurrent eczematoid rash, which responded poorly to conventional treatment, secondary infection, multiple episodes of hospitalisation for pulmonary infection, and raised serum IgE levels. One case had occasional vesicles, bullae, and crusted plaques over both the extremities. Genetic study was possible in only one of them who was found to have pathogenic homozygous deletions of exon-15 to 18 in DOCK8 gene following which he underwent bone marrow transplant (BMT), however, succumbed to lower respiratory tract infection two months after BMT and rest of them received multiple courses of antibiotics, oral/ topical steroids, and cyclosporine intermittently with variable response. Discussion: Our study highlights various characteristics, presentation, and management of this rare syndrome in children. Knowledge of these manifestations in skin of color will facilitate early identification and contribute to optimal care of the patients as representative data on the same is limited in literature.Keywords: absolute eosinophil count, atopic dermatitis, eczematous rash, hyper-immunoglobulin E syndrome, pulmonary infection, serum IgE, skin of color
Procedia PDF Downloads 138168 Investigating Role of Novel Molecular Players in Forebrain Roof-Plate Midline Invagination
Authors: Mohd Ali Abbas Zaidi, Meenu Sachdeva, Jonaki Sen
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In the vertebrate embryo, the forebrain anlagen develops from the anterior-most region of the neural tube which is the precursor of the central nervous system (CNS). The roof plate located at the dorsal midline region of the forebrain anlagen, acts as a source of several secreted molecules involved in patterning and morphogenesis of the forebrain. One such key morphogenetic event is the invagination of the forebrain roof plate which results in separation of the single forebrain vesicle into two cerebral hemispheres. Retinoic acid (RA) signaling plays a key role in this process. Blocking RA signaling at the dorsal forebrain midline inhibits dorsal invagination and results in the absence of certain key features of this region, such as thinning of the neuroepithelium and a lowering of cell proliferation. At present we are investigating the possibility of other signaling pathways acting in concert with RA signaling to regulate this process. We have focused on BMP signaling, which we found to be active in a mutually exclusive domain to that of RA signaling within the roof plate. We have also observed that there is a change in BMP signaling activity on modulation of RA signaling indicating an antagonistic relationship between the two. Moreover, constitutive activation of BMP signaling seems to completely inhibit thinning and partially affect invagination, leaving the lowering of cell proliferation in the midline unaffected. We are employing in-silico modeling as well as molecular manipulations to investigate the relative contribution if any, of regional differences in rates of cell proliferation and thinning of the neuroepithelium towards the process of invagination. We have found expression of certain cell adhesion molecules in forebrain roof-plate whose mRNA localization across the thickness of neuroepithelium is influenced by Bmp and RA signaling, giving regional rigidity to roof plate and assisting invagination. We also found expression of certain cytoskeleton modifiers in a localized small domains in invaginating forebrain roof plate suggesting that midline invagination is under control of many factors.Keywords: bone morphogenetic signaling, cytoskeleton, cell adhesion molecules, forebrain roof plate, retinoic acid signaling
Procedia PDF Downloads 155167 Formulation of Building Design Principles for Little People in Hong Kong
Authors: Yung Yau
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'Little people' are those who have extremely short stature as they suffer from rare bone diseases. They are commonly known as 'dwarves' or 'people with dwarfism'. Dwarfism is generally regarded as a type of rare disease for its extremely small odds (~1 in 15,000). On account of its rarity, dwarfism, unlike other types of disability, has attracted relatively little attention from the general public and in various academic fields (e.g. architecture, psychology and sociology) except medical science. In view of the extant research gaps, this study aims to investigate the physical barriers facing the little people in the built environment in Hong Kong. Between November 2017 and July 2018, ten little people or their family members participated in in-depth interviews. Responses of the interviewees were transcribed (i.e., speech being converted to text word for word). Interview data were then analyzed using the interpretative phenomenological analysis methodology developed by J. Smith and others in 2009. The findings of the project reveal that although Hong Kong's built environment has been designed barrier-free pursuant to the prevailing building standards, those standards do not cater to the special anthropometric characteristics of little people. As a result, little people face a lot of challenges when using built facilities. For example, most water closets, urinals, and wash hand basins are not fit for little people's use. As indicated by the project findings, we are still far away from providing a discrimination-free and barrier-free living environment for the little people in Hong Kong. To make Hong Kong society more inclusive to the little people, there is a need for further tailored building design. A set of building design principles for better inclusion of the little people in our society are highlighted. These principles include 'the building design should accommodate individuals with different heights' and 'the building design should allow individuals to use comfortably and efficiently with a minimum of fatigue'. At the end of the paper, the author also calls for an agenda for further studies. For instance, we need an anthropometric study on little people for developing practical building design guidelines.Keywords: dwarfism, little people, inclusive buildings, people with disabilities, social sustainability
Procedia PDF Downloads 129166 Establishment and Characterization of a Dentigerous Cyst Cell Line
Authors: Muñiz-Lino Marcos Agustín, Vazquez Borbolla Jessica, Licéaga-Escalera Carlos
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The ectomesenchymal tissues involved in tooth development and their remnants are the origin of different odontogenic lesions, including tumors and cysts of the jaws, with a wide range of clinical behaviors. Dentigerous cyst (DC) represents approximately 20% of all cases of odontogenic cysts, and it has been demonstrated that it can develop benign and malignant odontogenic tumors. DC is characterized by bone destruction of the area surrounding the crown of a tooth which has not erupted and it contain is liquid. The treatment of odontogenic tumors and cysts usually are partial or total removal of the jaw, causing important secondary co-morbidities. However, molecules implicated in DC pathogenesis as well in its development to odontogenic tumors remains unknown. A cellular model may be useful to study these molecules, but that model has not been established yet. Here, we reported the establishment of a cell culture derived from a dentigerous cyst. This cell line was named DeCy-1. In spite of its ectomesenchymal morphology, DeCy-1 cells express epithelial markers such as cytokeratins 5, 6, and 8. Furthermore, these cells express the ODAM protein, which is present in odontogenesis and in dental follicle, indicating that DeCy-1 cells derived from odontogenic epithelium. Analysis by electron microscopy of this cell line showed that it has a high vesicular activity, suggesting that DeCy-1 could secrete molecules that may be involved in DC pathogenesis. Thus, secreted proteins were analyzed by PAGE-SDS, where we observed approximately 11 bands. In addition, the capacity of these secretions to degrade proteins was analyzed by gelatin substrate zymography. A degradation band of about 62 kDa was found in these assays. Western blot assays suggested that the matrix metalloproteinase 2 (MMP-2) is responsible of this protease activity. Thus, our results indicate that the establishment of a cell line derived from DC is a useful in vitro model to study the biology of this odontogenic lesion and its participation in the development of odontogenic tumors.Keywords: dentigerous cyst, MMP20, cancer, cell culture
Procedia PDF Downloads 135165 Results of an Educative Procedure by Nursing on Patients Subjected to a Transplant from Hematopoietic Parents
Authors: C. Catalina Zapata, Z. Claudia Montoya
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Transplant from hematopoietic parents (THP) or medulla (MT) is a procedure used to replace the medulla that does not work as part of a disease or when it is destroyed either by a treatment of high medication doses against cancer or by radiation. The transplant process has three stages, a stage prior to transplant, during and after the transplant. It is held with the help of an interdisciplinary team, including nursing, carrying out mainly educative procedures to warrant the adhesion and the changes in lifestyles needed to whom will undergo this procedure. The aim of the study was to assess the results of an educative procedure by nursing, on adult patients subjected to a transplant from hematopoietic parents at a high complexity institution of Medellin city, Colombia. This study had an observational longitudinal design. According to the rules of protocol, the educative activity must be held on all patients joining the procedure. Four instruments were designed in order to collect all the information. One of them to measure the sociodemographic variables, another one to measure self-care practices, another one to measure transplant knowledge and its cares and the other one to measure the 30-day post-transplant complications. The last three instruments were applied before and after the educative procedure. A univaried analysis was carried out but the bivaried analysis was not carried out since there were not statistically meaningful differences before and after. Within the results, ten patients were evaluated. The average age was 38.2 (13.38 SD – standard deviation), 8/10 were men. Some self-care practices such us having pets and plants and consuming some specific food as well as little use of UV protection are all present in this type of patients and are not modified after the procedure. In measuring the knowledge, something stands out among the answers. It is the fact that some patients do not know what the medulla is, the nature of separating wastes at home and the need to consult about vomit and nausea. The most frequent complications during the first thirty days were: nausea, vomit, fever, and rash. They are considered to be expected within this period. Patients do not exhibit differences in their level of knowledge before and after the educative procedure by nursing. The patients’ self-care practices do not involve all the necessary ones to avoid complications. During the first 30 days, most of the complications are typical of the transplant process from hematopoietic parents.Keywords: bone marrow transplant, education, family, nursing, patients, Transplantation of hematopoietic progenitors
Procedia PDF Downloads 126164 Ageing Gingiva: A New Hope for Autologous Stem Cell Therapy
Authors: Ankush M. Dewle, Suditi Bhattacharya, Prachi R. Abhang, Savita Datar, Ajay J. Jog, Rupesh K. Srivastava, Geetanjali Tomar
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Objectives: The aim of this study was to investigate the quality of mesenchymal stem cells (MSCs) obtained from ageing gingival tissues, in order to suggest their potential role in autologous stem cell therapy for old individuals. Methods: MSCs were isolated from gingival tissues of young (18-45 years) and old (above 45 years) donors by enzymatic digestion. MSCs were analysed for cfu-f, surface marker expression by flow-cytometry and multilineage differentiation potential. The angiogenic potential was compared in a chick embryo yolk sac membrane model. The aging and differentiation markers including SA-β-galactosidase and p21 respectively were analysed by staining and flow-cytometry analysis. Additionally, osteogenic markers such as glucocorticoid receptor (GR), vitamin D receptor (VDR) were measured by flow-cytometry and RT-qPCR was performed for quantification of osteogenic gene expression. Alizarin Red S and alkaline phosphatase (ALP) activity were also quantitated. Results: Gingival MSCs (GMSCs) from both the age groups were similar in their morphology and displayed cfu-f. They had similar expression of MSC surface markers and p21, comparable rate of proliferation and differentiated to all the four lineages. GMSCs from young donors had a higher adipogenic differentiation potential as compared to the old GMSCs. Moreover, these cells did not display a significant difference in ALP activity probably due to comparable expression of GR, VDR, and osteogenic genes. Conclusions: Ageing of GMSCs occurs at a much slower rate than stem cells from other sources. Thus we suggest GMSCs as an excellent candidate for autologous stem cell therapy in degenerative diseases of elderly individuals. Clinical Significance: GMSCs could help overcome the setbacks in clinical implementation of autologous stem cell therapy for regenerative medicine in all age group of patient.Keywords: bone regeneration, cell therapy, senescence, stem cell
Procedia PDF Downloads 184163 Tibial Plateau Fractures During Covid-19 In A Trauma Unit. Impact of Lockdown and The Pressures on the Healthcare Provider
Authors: R. Gwynn, P. Panwalkar, K. Veravalli , M. Tofighi, R. Clement, A. Mofidi
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The aim of this study was to access the impact of Covid-19 and lockdown on the incidence, injury pattern, and treatment of tibial plateau fractures in a combined rural and urban population in wales. Methods: Retrospective study was performed to identify tibial plateau fractures in 15-month period of Covid-19 lockdown 15-month period immediately before lockdown. Patient demographics, injury mechanism, injury severity (based on Schatzker classification), and associated injuries, treatment methods, and outcome of fractures in the Covid-19 period was studied. Results: The incidence oftibial plateau fracture was 9 per 100000 during Covid-19, and 8.5 per 100000, and both were similar to previous studies. The average age was 52, and female to male ratio was 1:1 in both control and study group. High energy injury was seen in only 20% of the patients and 35% in the control groups (2=12, p<0025). 14% of the covid-19 population sustained other injuries as opposed 16% in the control group(2=0.09, p>0.95). Lower severity isolated lateral condyle fracturesinjury (Schatzker 1-3) were seen in 40% of fractures this was 60% in the control populations. Higher bicondylar and shaft fractures (Schatzker 5-6) were seen in 60% of the Covid-19 group and 35% in the control groups(2=7.8, p<0.02). Treatment mode was not impacted by Covid-19. The complication rate was low in spite of higher number of complex fractures and the impact of covid-19 pandemic. Conclusion: The associated injuries were similar in spite of a significantly lower mechanism of injury. There were unexpectedly worst tibial plateau fracture based Schatzker classification in the Covid-19 period as compared to the control groups. This was especially relevant for medial condyle and shaft fractures. This was postulated to be caused by reduction in bone density caused by lack of vitamin D and reduction in activity. The treatment mode and outcome was not impacted by the impact of Covid-19 on care for tibial plateau fractures.Keywords: Covid-19, knee, tibial plateau fracture, trauma
Procedia PDF Downloads 125162 Determination of the Volatile Organic Compounds, Antioxidant and Antimicrobial Properties of Microwave-Assisted Green Extracted Ficus Carica Linn Leaves
Authors: Pelin Yilmaz, Gizemnur Yildiz Uysal, Elcin Demirhan, Belma Ozbek
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The edible fig plant, Ficus carica Linn, belongs to the Moraceae family, and the leaves are mainly considered agricultural waste after harvesting. It has been demonstrated in the literature that fig leaves contain appealing properties such as high vitamins, fiber, amino acids, organic acids, and phenolic or flavonoid content. The extraction of these valuable products has gained importance. Microwave-assisted extraction (MAE) is a method using microwave energy to heat the solvents, thereby transferring the bioactive compounds from the sample to the solvent. The main advantage of the MAE is the rapid extraction of bioactive compounds. In the present study, the MAE was applied to extract the bioactive compounds from Ficus carica L. leaves, and the effect of microwave power (180-900 W), extraction time (60-180 s), and solvent to sample amount (mL/g) (10-30) on the antioxidant property of the leaves. Then, the volatile organic component profile was determined at the specified extraction point. Additionally, antimicrobial studies were carried out to determine the minimum inhibitory concentration of the microwave-extracted leaves. As a result, according to the data obtained from the experimental studies, the highest antimicrobial properties were obtained under the process parameters such as 540 W, 180 s, and 20 mL/g concentration. The volatile organic compound profile showed that isobergapten, which belongs to the furanocoumarins family exhibiting anticancer, antioxidant, and antimicrobial activity besides promoting bone health, was the main compound. Acknowledgments: This work has been supported by Yildiz Technical University Scientific Research Projects Coordination Unit under project number FBA-2021-4409. The authors would like to acknowledge the financial support from Tubitak 1515 - Frontier R&D Laboratory Support Programme.Keywords: Ficus carica Linn leaves, volatile organic component, GC-MS, microwave extraction, isobergapten, antimicrobial
Procedia PDF Downloads 80161 Giant Cancer Cell Formation: A Link between Cell Survival and Morphological Changes in Cancer Cells
Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika
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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine
Procedia PDF Downloads 217160 Biomechanics of Atalantoaxial Complex for Various Posterior Fixation Techniques
Authors: Arun C. O., Shrijith M. B., Thakur Rajesh Singh
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The study aims to analyze and understand the biomechanical stability of the atlantoaxial complex under different posterior fixation techniques using the finite element method in the Indian context. The conventional cadaveric studies performed show heterogeneity in biomechanical properties. The finite element method being a versatile numerical tool, is being wisely used for biomechanics analysis of atlantoaxial complex. However, the biomechanics of posterior fixation techniques for an Indian subject is missing in the literature. It is essential to study in this context as the bone density and geometry of vertebrae vary from region to region, thereby requiring different screw lengths and it can affect the range of motion(ROM), stresses generated. The current study uses CT images for developing a 3D finite element model with C1-C2 geometry without ligaments. Instrumentation is added to this geometry to develop four models for four fixation techniques, namely C1-C2 TA, C1LM-C2PS, C1LM-C2Pars, C1LM-C2TL. To simulate Flexion, extension, lateral bending, axial rotation, 1.5 Nm is applied to C1 while the bottom nodes of C2 are fixed. Then Range of Motion (ROM) is compared with the unstable model(without ligaments). All the fixation techniques showed more than 97 percent reduction in the Range of Motion. The von-mises stresses developed in the screw constructs are obtained. From the studies, it is observed that Transarticular technique is most stable in Lateral Bending, C1LM-C2 Translaminar is found most stable in Flexion/extension. The Von-Mises stresses developed minimum in Trasarticular technique in lateral bending and axial rotation, whereas stress developed in C2 pars construct minimum in Flexion/ Extension. On average, the TA technique is stable in all motions and also stresses in constructs are less in TA. Tarnsarticular technique is found to be the best fixation technique for Indian subjects among the 4 methods.Keywords: biomechanics, cervical spine, finite element model, posterior fixation
Procedia PDF Downloads 143159 Arthroscopic Fixation of Posterior Cruciate Ligament Avulsion Fracture through Posterior Trans Septal Portal Using Button Fixation Device: Mini Tight Rope
Authors: Ratnakar Rao, Subair Khan, Hari Haran
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Posterior cruciate ligament (PCL) avulsion fractures is a rare condition and commonly mismanaged.Surgical reattachment has been shown to produce better result compared with conservative management.Only few techniques are reported in arthroscopic fixation of PCL Avulsion Fracture and they are complex.We describe a new technique in fixation of the PCL Avulsion fracture through a posterior trans septal portal using button fixation device (Mini Tight Rope). Eighteen patients with an isolated posterior cruciate ligament avulsion fracture were operated under arthroscopy. Standard Antero Medial Portal and Antero Lateral portals made and additional Postero Medial and Postero Lateral portals made and trans Septal portal established. Avulsion fracture identified, elevated, prepared. Reduction achieved using PCL Tibial guide (Arthrex) and fixation was achieved using Mini Tight Rope,Arthrex (2 buttons with a suture). Reduction confirmed using probe and Image intensifier. Postoperative assessment made clinically and radiologically. 15 patients had good to excellent results with no posterior sag or instability. The range of motion was normal. No complications were recorded per operatively. 2 patients had communition of the fragment while drilling, for one patient it was managed by suturing technique and the second patient PCL Reconstruction was done. One patient had persistent instability with poor outcome. Establishing trans septal portal helps in better visualization of the posterior compartment of the knee. Assessment of the bony fragment, preparation 0f the bone bed andit protects from injury to posterior neurovascular structures. Fixation using the button with suture (Mini Tight Rope) is stable and easily reproducible for PCL Avulsion fracture with single large fragment.Keywords: PCL avulsion, arthroscopy, transeptal, minitight rope technique
Procedia PDF Downloads 256158 Levels of CTX1 in Premenopausal Osteoporotic Women Study Conducted in Khyberpuktoonkhwa Province, Pakistan
Authors: Mehwish Durrani, Rubina Nazli, Muhammad Abubakr, Muhammad Shafiq
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Objectives: To evaluate the high socio-economic status, urbanization, and decrease ambulation can lead to early osteoporosis in women reporting from Peshawar region. Study Design: Descriptive cross-sectional study was done. Sample size was 100 subjects, using 30% proportion of osteoporosis, 95% confidence level, and 9% margin of error under WHO software for sample size determination. Place and Duration of study: This study was carried out in the tertiary referral health care facilities of Peshawar viz PGMI Hayatabad Medical Complex, Peshawar, Khyber Pakhtunkhwa Province, Pakistan. Ethical approval for the study was taken from the Institutional Ethical Research board (IERD) at Post Graduate Medical Institute, Hayatabad Medical Complex, and Peshawar.The study was done in six months time period. Patients and Methods: Levels of CTX1 as a marker of bone degradation in radiographically assessed perimenopausal women was determined. These females were randomly selected and screened for osteoporosis. Hemoglobin in gm/dl, ESR by Westergren method as millimeter in 1 hour, Serum Ca mg/dl, Serum alkaline Phosphatase international units per liter radiographic grade of osteoporosis according to Singh index as 1-6 and CTX 1 level in pg/ml. Results: High levels of CTX1 was observed in perimenopausal osteoporotic women which were radiographically diagnosed as osteoporotic patients. The High socio-economic class also predispose to osteoporosis. Decrease ambulation another risk factor showed significant association with the increased levels of CTX1. Conclusion: The results of this study propose that minimum ambulation and high socioeconomic class both had significance association with the increase levels of serum CTX1, which in turn will lead to osteoporosis and to its complications.Keywords: osteoporosis, CTX1, perimenopausal women, Hayatabad Medical Complex, Khyberpuktoonkhwa
Procedia PDF Downloads 331157 Diaper Dermatitis and Pancytopenia as the Primary Manifestation in an Infant with Vitamin B12 Deficiency
Authors: Ekaterina Sánchez Romero, Emily Gabriela Aguirre Herrera, Sandra Luz Espinoza Esquerra, Jorge García Campos
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Female, 7 months old, daughter of a mother with anemia during pregnancy, with no history of atopy in the family, since birth she presents with recurrent dermatological and gastrointestinal infections, chronically treated for recurrent diaper dermatitis. At 6 months of age, she begins with generalized pallor, hyperpigmentation in hands and feet, smooth tongue, psychomotor retardation with lack of head support, sedation, and hypoactivity. She was referred to our hospital for a fever of 38°C, severe diaper rash, and pancytopenia with HB 9.3, platelets 38000, neutrophils 0.39 MCV: 86.80 high for her age. The approach was initiated to rule out myeloproliferative syndrome, with negative immunohistochemical results of bone marrow aspirate; during her stay, she presented neurological regression, lack of sucking, and focal seizures. CT scan showed cortical atrophy. The patient was diagnosed with primary immunodeficiency due to history; gamma globulin was administered without improvement with normal results of immunoglobulins and metabolic screening. When dermatological and neurological diagnoses were ruled out as the primary cause, a nutritional factor was evaluated, and a therapeutic trial was started with the administration of vitamin B12 and zinc, presenting clinical neurological improvement and resolution of pancytopenia in 2 months. It was decided to continue outpatient management. Discussion: We present a patient with neurological, dermatological involvement, and pancytopenia, so the most common differential diagnoses in this population were ruled out. Vitamin B12 deficiency is an uncommon entity. Due to maternal and clinical history, a therapeutic trial was started resulting in an improvement. Conclusion: VitaminB12 deficiency should be considered one of the differential diagnoses in the approach to pancytopenia with megaloblastic anemia associated with dermatologic and neurologic manifestations. Early treatment can reduce irreversible damage in these patients.Keywords: vitamin B12 deficiency, pediatrics, pancytopenia, diaper dermatitis
Procedia PDF Downloads 98156 Characterization of Dota-Girentuximab Conjugates for Radioimmunotherapy
Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler
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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer
Procedia PDF Downloads 307155 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity
Authors: Fumihiro Ima, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi
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It is important to know growth rate of brain tumors before surgery because it influences treatment planning including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without administration of contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients and WHO grade 4 in 2 patients), meningioma WHO grade1 in 2 patients and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW-signals than that in low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW-signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation
Procedia PDF Downloads 139154 Solitary Fibrous Tumor Presumed to Be a Peripheral Nerve Sheath Tumor Involving Right Branchial Plexus
Authors: Daniela Proca, Yuan Rong, Salvatore Luceno, Jalil Nasibli
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Introduction: Solitary Fibrous Tumors (SFT) have many histologic mimickers and the only way to diagnose it, particularly in an unusual location, such as peripheral nerve trunks, is to use a comprehensive immunohistochemical staining panel. Monoclonal STAT6 immunostain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases. Methods: We describe a solitary fibrous tumor (SFT) involving the right branchial plexus in a 66 yo female with 4-year history of slowly growing chest wall mass with recent dysesthesias in fingers 4th and 5th. MRI showed a well-circumscribed heterogenous mass measuring 5.4 x 3.8 x 4.0 cm and encircling peripheral nerves of the branchial plexus; no involvement of the bone or muscle was noted. A biopsy showed a bland spindled and epithelioid proliferation with no significant mitotic activity, no necrosis, and no atypia; peripheral nerve fascicles were encircled by the lesion. The main clinical and pathologic differential diagnosis included peripheral nerve sheath tumor, particularly schwannoma; HE microscopy didn’t show the classic Antoni A and B areas but showed focal subtle nuclear palisading, as well as prominent vessels with hyalinization. Immunohistochemical stains showed focal, weak cytoplasmic S100 positivity in the lesion; CD 34 and Vimentin were strongly and diffusely positive; the neoplastic cells were negative with AE1/AE3, EMA, CD31, SMA, Desmin, Calretinin, HMB-45, Melan A, PAX-8, NSE. The immunohistochemical and histologic pattern was not typical of peripheral nerve sheath tumor. On additional stains, the tumor was positive with STAT-6 and bcl-2 and focally positive with CD99. Given this profile, the final diagnosis was that of a solitary fibrous tumor. Results: NA Conclusion: Very few SFTs involving peripheral nerves and mimicking a peripheral nerve sheath tumor are described in the literature. Although histologically benign on this biopsy, long-term follow-up is required because of the risk of recurrence of these tumors and their uncertain biological behavior.Keywords: solitary fibrous tumor, pathology, diagnosis, immunohistochemistry
Procedia PDF Downloads 196153 Phenotypic Characterization of Desi Naked Neck Chicken and Its Association with Insulin-Like Growth Factor-I (IGF-I) Gene Polymorphism in Pakistan
Authors: Akbar Nawaz Khan, Abdul Ghaffar, Muhammad Naeem Riaz
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The study was conducted to investigate the phenotypic features, morphometry and production potentialities of indigenous naked neck chicken (NN) of Pakistan under intensive management condition. A total of 35 NN chicks were randomly selected, and the experiment was performed at Poultry and wildlife research section NARC Islamabad for a period of 22 weeks. The predominant plumage color was black and golden while skin color was observed white. The average shank length, leg length, thigh length, keel length, chest breadth, head width, wing space, wing length, body length, body girth, body height and pubic bone width in adult males and females were 69.19 ± 3.34mm, 117.93 ± 4.42mm, 117.93 ± 4.42mm, 90.87 ± 6.53mm, 95.03 ± 4.56mm, 49.77 ± 2.53mm, 30.63 ± 1.50cm, 27.24 ± 2.71cm, 18.88 ± 0.65cm, 17.77 ± 1.01cm, 25.96 ± 0.56cm, 47.81 ± 1.41cm and 35.69 ± 4.09mm respectively. The average age and live body weight of NN chicken at sexual maturity were recorded as 165.85 days and 1269.38 g. While hen-day egg production of NN was recorded as 45%. The present study was aimed to investigate the existence of polymorphism at IGF-I gene in indigenous naked neck chicken through PCR based Restriction Fragment Length Polymorphism. Based on restriction analysis using Hinf I restriction enzyme, three genotypes were detected designated as AA, AC, and CC. Restriction analysis of PCR amplified product showed the presence of DNA fragments of 622, 378, 244 and 191, (genotypes). The PCR-RFLP analysis is easy, cost effective method which permits the easy characterization of IGF-I gene. This showed the investigated IGF-I genes can serve as good molecular markers for marker assisted selection (MAS) concerning growth related traits in chicken.Keywords: Desi chicken, naked neck, morphology, morphometry, production potential, egg traits, egg geometry, IGF-I, growth, PCR- RFLP, chicken
Procedia PDF Downloads 389152 Computation of Radiotherapy Treatment Plans Based on CT to ED Conversion Curves
Authors: B. Petrović, L. Rutonjski, M. Baucal, M. Teodorović, O. Čudić, B. Basarić
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Radiotherapy treatment planning computers use CT data of the patient. For the computation of a treatment plan, treatment planning system must have an information on electron densities of tissues scanned by CT. This information is given by the conversion curve CT (CT number) to ED (electron density), or simply calibration curve. Every treatment planning system (TPS) has built in default CT to ED conversion curves, for the CTs of different manufacturers. However, it is always recommended to verify the CT to ED conversion curve before actual clinical use. Objective of this study was to check how the default curve already provided matches the curve actually measured on a specific CT, and how much it influences the calculation of a treatment planning computer. The examined CT scanners were from the same manufacturer, but four different scanners from three generations. The measurements of all calibration curves were done with the dedicated phantom CIRS 062M Electron Density Phantom. The phantom was scanned, and according to real HU values read at the CT console computer, CT to ED conversion curves were generated for different materials, for same tube voltage 140 kV. Another phantom, CIRS Thorax 002 LFC which represents an average human torso in proportion, density and two-dimensional structure, was used for verification. The treatment planning was done on CT slices of scanned CIRS LFC 002 phantom, for selected cases. Interest points were set in the lungs, and in the spinal cord, and doses recorded in TPS. The overall calculated treatment times for four scanners and default scanner did not differ more than 0.8%. Overall interest point dose in bone differed max 0.6% while for single fields was maximum 2.7% (lateral field). Overall interest point dose in lungs differed max 1.1% while for single fields was maximum 2.6% (lateral field). It is known that user should verify the CT to ED conversion curve, but often, developing countries are facing lack of QA equipment, and often use default data provided. We have concluded that the CT to ED curves obtained differ in certain points of a curve, generally in the region of higher densities. This influences the treatment planning result which is not significant, but definitely does make difference in the calculated dose.Keywords: Computation of treatment plan, conversion curve, radiotherapy, electron density
Procedia PDF Downloads 486151 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity
Authors: Fumihiro Imai, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi
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It is important to know the growth rate of brain tumors before surgery because it influences treatment planning, including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without the administration of a contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after a clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients, and WHO grade 4 in 2 patients), meningioma WHO grade 1 in 2 patients, and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW signals than that low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation
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