Search results for: pediatric tumor
456 Nasopharyngeal Carriage of Streptococcus pneumoniae in Children under 5 Years of Age before Introduction of Pneumococcal Vaccine (PCV 10) in Urban and Rural Sindh
Authors: Muhammad Imran Nisar, Fyezah Jehan, Tauseef Akhund, Sadia Shakoor, Kanwal Nayani, Furqan Kabir, Asad Ali, Anita Zaidi
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Pneumococcal Vaccine -10 (PCV 10) was included in the Expanded Program of immunization (EPI) in Sindh, Pakistan in February 2013. This study was carried out immediately before the introduction of PCV 10 to establish baseline pneumococcal carriage and prevalent serotypes in naso-pharynx of children 3-11 months of age in an urban and rural community in Sindh, Pakistan. An additional sample of children aged 12 to 59 months was drawn from the urban community. Nasopharyngeal specimens were collected from a random sample of children. Samples were processed in a central laboratory in Karachi. Pneumococci were cultured on 5% Sheep Blood Agar and serotyping was performed using CDC standardized sequential multiplex PCR assay on bacterial colonies. Serotypes were then categorized into vaccine (PCV-10 and PCV-13) type and non-vaccine types. A total of 670 children were enrolled. Carriage rate for pneumococcus based on culture positivity was 74% and 79.5 % in the infant group in Karachi and Matiari respectively. Carriage rate was 78.2% for children aged 12 to 59 months in Karachi. Proportion of PCV 10 serotypes in infants was 38.8% and 33.5% in Karachi and Matiari respectively. In the older age group in Karachi, the proportion was 30.6%. Most common serotypes were 6A, 6B, 23F, 19A and 18C. This survey establishes vaccine and non-vaccine serotype carriage rate in a vaccine-naïve pediatric population among rural and urban communities in Sindh province. Annually planned surveys in the same communities will inform change in carriage rate after the introduction and uptake of PCV 10 in these communities.Keywords: Naso-Pharyngeal carriage, Pakistan, PCV10, Pneumococcus
Procedia PDF Downloads 300455 Investigation of the Functional Impact of Amblyopia on Visual Skills in Children
Authors: Chinmay V. Deshpande
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Purpose: To assess the efficiency of visual functions and visual skills in strabismic & anisometropic amblyopes and to assess visual acuity and contrast sensitivity in anisometropic amblyopes with spectacles & contact lenses. Method: In a prospective clinical study, 32 children ageing from 5 to 15 years presenting with amblyopia in a pediatric department of Shri Ganapati Netralaya Jalna, India, were assessed for a period of three & half months. Visual acuity was measured with Snellen’s and Bailey-Lovie log MAR charts whereas contrast sensitivity was measured with Pelli-Robson chart with spectacles and contact lenses. Saccadic movements were assessed with SCCO scoring criteria and accommodative facility was checked with ±1.50 DS flippers. Stereopsis was assessed with TNO test. Results: By using Wilcoxon sign rank test p-value < 0.05 (< 0.001), the mean linear visual acuity was 0.29 (≈ 6/21) and mean single optotype visual acuity found to be 0.36 (≈ 6/18). Mean visual acuity of 0.27(≈ 6/21) with spectacles improved to 0.33 (≈ 6/18) with contact lenses in amblyopic eyes. The mean Log MAR visual acuity with spectacles and contact lens were found to be 0.602( ≈6/24) and 0.531(≈ 6/21) respectively. The contrast threshold out of 20 amblyopic eyes shows that mean contrast threshold changed in 9 patients from spectacles 0.27 to contact lens 0.19 respectively. The mean accommodative facility assessed was 5.31(± 2.37). 24 subjects (75%) revealed marked saccadic defects on the test applied. 78% subjects didn’t show even gross stereoscopic ability on TNO test. Conclusion: This study supports the facts about amblyopia and associated deficits in visual skills which are claimed in previous studies. In addition, anisometropic amblyopia can be managed better with contact lenses.Keywords: strabismus, anisometropia, amblyopia, contrast sensitivity, saccades, stereopsis
Procedia PDF Downloads 421454 Modeling Waiting and Service Time for Patients: A Case Study of Matawale Health Centre, Zomba, Malawi
Authors: Moses Aron, Elias Mwakilama, Jimmy Namangale
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Spending more time on long queues for a basic service remains a common challenge to most developing countries, including Malawi. For health sector in particular, Out-Patient Department (OPD) experiences long queues. This puts the lives of patients at risk. However, using queuing analysis to under the nature of the problems and efficiency of service systems, such problems can be abated. Based on a kind of service, literature proposes different possible queuing models. However, unlike using generalized assumed models proposed by literature, use of real time case study data can help in deeper understanding the particular problem model and how such a model can vary from one day to the other and also from each case to another. As such, this study uses data obtained from one urban HC for BP, Pediatric and General OPD cases to investigate an average queuing time for patients within the system. It seeks to highlight the proper queuing model by investigating the kind of distributions functions over patient’s arrival time, inter-arrival time, waiting time and service time. Comparable with the standard set values by WHO, the study found that patients at this HC spend more waiting times than service times. On model investigation, different days presented different models ranging from an assumed M/M/1, M/M/2 to M/Er/2. As such, through sensitivity analysis, in general, a commonly assumed M/M/1 model failed to fit the data but rather an M/Er/2 demonstrated to fit well. An M/Er/3 model seemed to be good in terms of measuring resource utilization, proposing a need to increase medical personnel at this HC. However, an M/Er/4 showed to cause more idleness of human resources.Keywords: health care, out-patient department, queuing model, sensitivity analysis
Procedia PDF Downloads 435453 Surgical Collaboration in Managing Spinal Cord Compression Due to a Pre-Vertebral Chordoma: A Case Report
Authors: Rose Virginy S. Bautista, Ida Marie Tabangay-Lim, Helen Bongalon-Amo, Jose Modesto B. Abellera
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Chordomas, particularly those of the spine and the head and neck region, represent a rare and locally aggressive group of malignancies. The complexity of these tumors -given the rarity, location, and involvement of neurovascular structures- imposes a challenge in the diagnosis and management. We herein report a case of spinal cord compression due to a prevertebral cervical chordoma. The patient presented with a gradually enlarging lateral neck mass, with progressive bilateral extremity weakness and urinary incontinence; preoperative biopsy showed chordoma. A multidisciplinary approach for the management of this case was made, involving neurosurgery, head and neck surgery, and radiation oncology services. Surgical collaboration between the two cutting services was done to have a radical excision of the tumor and spinal cord decompression. The patient was then referred for adjuvant radiation therapy. With this collaborative treatment strategy, more comprehensive and quality care could be provided to our patients.Keywords: chordoma, surgical collaboration, spinal cord compression, neurosurgery, head and neck surgery
Procedia PDF Downloads 69452 The Transport of Radical Species to Single and Double Strand Breaks in the Liver’s DNA Molecule by a Hybrid Method of Type Monte Carlo - Diffusion Equation
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The therapeutic utility of certain Auger emitters such as iodine-125 depends on their position within the cell nucleus . Or diagnostically, and to maintain as low as possible cell damage, it is preferable to have radionuclide localized outside the cell or at least the core. One solution to this problem is to consider markers capable of conveying anticancer drugs to the tumor site regardless of their location within the human body. The objective of this study is to simulate the impact of a complex such as bleomycin on single and double strand breaks in the DNA molecule. Indeed, this simulation consists of the following transactions: - Construction of BLM -Fe- DNA complex. - Simulation of the electron’s transport from the metastable state excitation of Fe 57 by the Monte Carlo method. - Treatment of chemical reactions in the considered environment by the diffusion equation. For physical, physico-chemical and finally chemical steps, the geometry of the complex is considered as a sphere of 50 nm centered on the binding site , and the mathematical method used is called step by step based on Monte Carlo codes.Keywords: concentration, yield, radical species, bleomycin, excitation, DNA
Procedia PDF Downloads 457451 Clinical Profile and Outcome of Type I Diabetes Mellitus at a Tertiary Care-Centre in Eastern Nepal
Authors: Gauri Shankar Shah
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Objectives: The Type I diabetes mellitus in children is frequently a missed diagnosis and children presents in emergency with diabetic ketoacidosis having significant morbidity and mortality. The present study was done to find out the clinical presentation and outcome at a tertiary-care centre. Methods: This was retrospective analysis of data of Type I diabetes mellitus reporting to our centre during last one year (2012-2013). Results: There were 12 patients (8 males) and the age group was 4-14 years (mean ± 3.7). The presenting symptoms were fever, vomiting, altered sensorium and fast breathing in 8 (66.6%), 6 (50%), 4 (33.3%), and 4 (33.3%) cases, respectively. The classical triad of polyuria, polydypsia, and polyphagia were present only in two patients (33.2%). Seizures and epigastric pain were found in two cases each (33.2%). The four cases (33.3%) presented with diabetic ketoacidosis due to discontinuation of insulin doses, while 2 had hyperglycemia alone. The hemogram revealed mean hemoglobin of 12.1± 1.6 g/dL and total leukocyte count was 22,883.3 ± 10,345.9 per mm3, with polymorphs percentage of 73.1 ± 9.0%. The mean blood sugar at presentation was 740 ± 277 mg/ dl (544–1240). HbA1c ranged between 7.1-8.8 with mean of 8.1±0.6 %. The mean sodium, potassium, blood ph, pCO2, pO2 and bicarbonate were 140.8 ± 6.9 mEq/L, 4.4 ± 1.8mEq/L, 7.0 ± 0.2, 20.2 ± 10.8 mmHg, 112.6 ± 46.5 mmHg and 9.2 ± 8.8 mEq/L, respectively. All the patients were managed in pediatric intensive care unit as per our protocol, recovered and discharged on intermediate insulin given twice daily. Conclusions: Thus, it shows that these patients have uncontrolled hyperglycemia and often presents in emergency with ketoacidosis and deranged biochemical profile. The regular administration of insulin, frequent monitoring of blood sugar and health education are required to have better metabolic control and good quality of life.Keywords: type I diabetes mellitus, hyperglycemia, outcome, glycemic control
Procedia PDF Downloads 254450 Central Nervous System Lesion Differentiation in the Emergency Radiology Department
Authors: Angelis P. Barlampas
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An 89 years old woman came to the emergency department complaining of long-lasting headaches and nausea. A CT examination was performed, and a homogeneous midline anterior cranial fossa lesion was revealed, which was situated near the base and measured 2,4 cm in diameter. The patient was allergic, and an i.v.c injection could not be done on the spot, and neither could an MRI exam because of metallic implants. How could someone narrow down the differential diagnosis? The interhemispheric meningioma is usually a silent midline lesion with no edema, and most often presents as a homogeneous, solid type, isodense, or slightly hyperdense mass ( usually the smallest lesions as this one ). Of them, 20-30% have some calcifications. Hyperostosis is typical for meningiomas that abut the base of the skull but is absent in the current case, presumably of a more cephalad location that is borderline away from the bone. Because further investigation could not be done, as the patient was allergic to the contrast media, some other differential options should be considered. Regarding the site of the lesion, the most common other entities to keep in mind are the following: Metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma, giant aneurysm of the anterior cerebral artery, midline lesion. Appearance will depend on whether the aneurysm is non-thrombosed, or partially, or completely thrombosed. Non-contrast: slightly hyperdense, well-defined round extra-axial mass, may demonstrate a peripheral calcified rim, olfactory neuroblastoma, midline lesion. The mass is of soft tissue attenuation and is relatively homogeneous. Focal calcifications are occasionally present. When an intracranial extension is present, peritumoral cysts between it and the overlying brain are often present. Final diagnosis interhemispheric meningioma (Known from the previous patient’s history). Meningiomas come from the meningocytes or the arachnoid cells of the meninges. They are usually found incidentally, have an indolent course, and their most common location is extra-axial, parasagittal, and supratentorial. Other locations include the sphenoid ridge, olfactory groove, juxtasellar, infratentorial, intraventricular, pineal gland area, and optic nerve meningioma. They are clinically silent entities, except for large ones, which can present with headaches, changes in personality status, paresis, or symptomatology according to their specific site and may cause edema of the surrounding brain tissue. Imaging findings include the presence of calcifications, the CSF cleft sign, hyperostosis of adjacent bone, dural tail, and white matter buckling sign. After i.v.c. injection, they enhance brightly and homogenously, except for large ones, which may exhibit necrotic areas or may be heavily calcified. Malignant or cystic variants demonstrate more heterogeneity and less intense enhancement. Sometimes, it is inevitable that the needed CT protocol cannot be performed, especially in the emergency department. In these cases, the radiologist must focus on the characteristic imaging features of the unenhanced lesion, as well as in previous examinations or a known lesion history, in order to come to the right report conclusion.Keywords: computed tomography, emergency radiology, metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma
Procedia PDF Downloads 69449 Homing of B Cells via Afferent Lymphatics
Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster
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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection
Procedia PDF Downloads 263448 Delivery of Doxorubicin to Glioblastoma Multiforme Using Solid Lipid Nanoparticles with Surface Aprotinin and Melanotransferrin Antibody for Enhanced Chemotherapy
Authors: Yung-Chih Kuo, I-Hsuan Lee
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Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin
Procedia PDF Downloads 361447 The Effect of Thymoquinone and Sorafenib Combination on Hepatocellular Carcinoma Cell Line
Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail
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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone
Procedia PDF Downloads 554446 Assessment of Nurse's Knowledge Toward Infection Control for Wound Care in Governmental Hospital at Amran City-Yemen
Authors: Fares Mahdi
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Background: Infection control is an important concern for all health care professionals, especially nurses. Nurses have a higher risk for both self-acquiring and transmitting infections to other patients. Aim of this study: to assess nurses' knowledge regarding infection control for wound care. Methodology: a descriptive research design was used in the study. The total number studied sample was 200 nurses, were conducting in Amran Public Hospitals in Amran City- Yemen. The study covered sample nurses in the hospital according to the study population; a standard closed-ended questionnaire was used to collect the data. Results: The results showed less than half (37.5 %) of nurses were from 22 May Hospital, also followed by (62.5%) of them were from Maternal and Child Hospital. Also according to the department name. Most (22.5%) of nurses worked in an intensive care unit, followed by (20%) of them were working in the pediatric world, also about (19%) of them were working in the surgical department. While in finally, only about (8.5%) of them worked from another department. According to course training, The results showed about (21%) of nurses had course training in wound care management. At the same time, others (79%) of them have not had course training in wound care management. According to the total nurse's knowledge of infection control for wound care, that find more than two-thirds (68%) of nurses had fair knowledge according to total all of nurse's knowledge of infection control wound care. Conclusion:The results showed that more than two-thirds (68%) of nurses had fair knowledge according to total all of the nurse's knowledge of infection control for wound care. Recommendations: There should be providing training program about infection control masseurs and it's important for new employees of nurses. Providing continuing refreshment training courses about infection control programs and about evidence-based practice in infection control for all health care teams.Keywords: assessment, knowledge, infection control, wound care, nurses, amran hospitals
Procedia PDF Downloads 95445 The Impact of Pediatric Cares, Infections and Vaccines on Community and People’s Lives
Authors: Nashed Atef Nashed Farag
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Introduction: Reporting adverse events following vaccination remains a challenge. WHO has mandated pharmacovigilance centers around the world to submit Adverse Events Following Immunization (AEFI) reports from different countries to a large electronic database of adverse drug event data called Vigibase. Despite sufficient information about AEFIs on Vigibase, they are not available to the general public. However, the WHO has an alternative website called VigiAccess, an open-access website that serves as an archive for reported adverse reactions and AEFIs. The aim of the study was to establish a reporting model for a number of commonly used vaccines in the VigiAccess system. Methods: On February 5, 2018, VigiAccess comprehensively searched for ESSI reports on the measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine, and tuberculosis vaccine (BCG). These are reports from all pharmacovigilance centers around the world since they joined the WHO Drug Monitoring Program. Results: After an extensive search, VigiAccess found 9,062 AEFIs from the measles vaccine, 185,829 AEFIs from the OPV vaccine, 24,577 AEFIs from the yellow fever vaccine, 317,208 AEFIs from the pneumococcal vaccine, 73,513 AEFIs from the rotavirus vaccine, and 145,447 AEFIs from meningococcal cal vaccine, 22,781 EI FI vaccines against tetanus and 35,556 BCG vaccines against AEFI. Conclusion: The study found that among the eight vaccines examined, pneumococcal vaccines were associated with the highest number of AEFIs, while measles vaccines were associated with the fewest AEFIs.Keywords: surgical approach, anatomical approach, decompression, axillary nerve, quadrangular space adverse events following immunization, cameroon, COVID-19 vaccines, nOPV, ODK vaccines, adverse reactions, VigiAccess, adverse event reporting
Procedia PDF Downloads 72444 Enhanced Magnetic Hyperthermic Efficiency of Ferrite Based Nanoparticles
Authors: J. P. Borah, R. D. Raland
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Hyperthermia is one of many techniques used destroys cancerous cell. It uses the physical methods to heat certain organ or tissue delivering an adequate temperature in an appropriate period of time, to the entire tumor volume for achieving optimal therapeutic results. Magnetic Metal ferrites nanoparticles (MFe₂O₄ where M = Mn, Zn, Ni, Co, Mg, etc.) are one of the most potential candidates for hyperthermia due to their tunability, biocompatibility, chemical stability and notable ability to mediate high rate of heat induction. However, to obtain the desirable properties for these applications, it is important to optimize their chemical composition, structure and magnetic properties. These properties are mainly sensitive to cation distribution of tetrahedral and octahedral sites. Among the ferrites, zinc ferrite (ZnFe₂O₄) and Manganese ferrite ((MnFe₂O₄) is one of a strong candidate for hyperthermia application because Mn and zinc have a non-magnetic cation and therefore the magnetic property is determined only by the cation distribution of iron, which provides a better platform to manipulate or tailor the properties. In this talk, influence of doping and surfactant towards cation re-distribution leading to an enhancement of magnetic properties of ferrite nanoparticles will be demonstrated. The efficiency of heat generation in association with the enhanced magnetic property is also well discussed in this talk.Keywords: magnetic nanoparticle, hyperthermia, x-ray diffraction, TEM study
Procedia PDF Downloads 164443 O-(2-18F-Fluoroethyl)-L-Tyrosine Positron Emission Tomography/Computed Tomography in Patients with Suspicious Recurrent Low and High-Grade Glioma
Authors: Mahkameh Asadi, Habibollah Dadgar
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The precise definition margin of high and low-grade glioma is crucial for choosing best treatment approach after surgery and radio-chemotherapy. The aim of the current study was to assess the O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET)/computed tomography (CT) in patients with low (LGG) and high grade glioma (HGG). We retrospectively analyzed 18F-FET PET/CT of 10 patients (age: 33 ± 12 years) with suspicious for recurrent LGG and HGG. The final decision of recurrence was made by magnetic resonance imaging (MRI) and registered clinical data. While response to radio-chemotherapy by MRI is often complex and sophisticated due to the edema, necrosis, and inflammation, emerging amino acid PET leading to better interpretations with more specifically differentiate true tumor boundaries from equivocal lesions. Therefore, integrating amino acid PET in the management of glioma to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.Keywords: positron emission tomography, amino acid positron emission tomography, magnetic resonance imaging, low and high grade glioma
Procedia PDF Downloads 176442 Azadirachta indica Derived Protein Encapsulated Novel Guar Gum Nanocapsules against Colon Cancer
Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar
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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein
Procedia PDF Downloads 177441 Relationship between Physical Activity Level and Functional Movement in 16-years old Schoolchildren: A Multilevel Modelling Approach
Authors: Josip Karuc, Marjeta Mišigoj-Duraković, Goran Marković, Vedran Hadžić, Michael J. Duncan, Hrvoje Podnar, Maroje Sorić
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As a part of the CRO-PALS longitudinal study, this investigation aimed to examine the association between different levels of physical activity (PA) and movement quality in 16-years old school children. The total number of participants in this research was 725. Movement quality was assessed via the Functional Movement Screen (FMSTM), and the PA level was estimated using the School Health Action, Planning, and Evaluation System (SHAPES) questionnaire. In addition, body fat and socioeconomic status (SES) were assessed. In order to investigate the association between total FMS score and different levels of PA, multilevel modeling was employed for boys (n=359) and girls (n=366) separately. All models were adjusted for age, body fat, and SES. Among boys, MVPA, MPA, and VPA were not significant predictors of the total FMS score (β=0.000, p=0.78; β=-0.002, p=0.455; β=0.004, p=0.158, respectively). On the contrary, among girls, VPA and MVPA showed significant effects on the total FMS score (β=0.011, p=0.001, β=0.005, p=0.006, respectively). The findings of this research provide evidence that the intensity of PA is a minor but relevant factor in describing the association between PA and movement quality in adolescent girls but not in boys. This means that the PA level does not guarantee optimal functional movement patterns. Therefore, practicing functional movement patterns in an isolated manner and at moderate to vigorous intensity could be beneficial in order to reduce the risk of injury incidence and potential orthopedic abnormalities in later life. This work was supported by the Croatian Science Foundation, grant no: IP-2016-06-9926 and grant no: DOK-2018-01-2328.Keywords: functional movement screen, fundamental movement patterns, movement quality, pediatric
Procedia PDF Downloads 161440 Lymphatic Microvessel Density as a Prognostic Factor in Endometrial Carcinoma
Authors: Noha E. Hassan
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Little is known regarding the influence of lymphatic microvessel density (LMVD) on prognosis in endometrial cancer. Prospective study was done in tertiary education and research hospital (Shatby Alexandria university hospital) on sixty patients presented with endometrial carcinoma underwent complete surgical staging. Our aim was to assess the intratumoral and peritumoral Lymphatic microvessel density (LMVD) of endometrial carcinomas identified by immunohistochemical staining using an antibody against podoplanin and to investigate their association with classical clinicopathological factors and prognosis. The result shows that high LMVD was associated with endometroid type of tumors, lesser myometrial, adnexal, cervical and peritoneal infiltration, lower tumor grade and stage and lesser recurrent cases. There is lower lymph node involvement among cases with high intratumoral LMVD and cases of high peritumoral LMVD; that reach statistical significance only among cases of high intratumoral LMVD. No association was seen between LMVD and lymphovascular space invasion. On the other hand, low LMVD was associated with poor outcome. Finally, we can conclude that increased LMVD is associated with favorable prognosis in endometrial cancer patients.Keywords: endometrial carcinoma, lymphatic microvessel, microvessel density, prognosis
Procedia PDF Downloads 141439 The Effects of the Interaction between Prenatal Stress and Diet on Maternal Insulin Resistance and Inflammatory Profile
Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa
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Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha
Procedia PDF Downloads 200438 Clonal Evaluation of Malignant Mesothelioma
Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone
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Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas
Procedia PDF Downloads 458437 Relationship between Trauma and Acute Scrotum: Test Torsion and Epididymal Appendix Torsion
Authors: Saimir Heta, Kastriot Haxhirexha, Virtut Velmishi, Nevila Alliu, Ilma Robo
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Background: Testicular rotation can occur at any age. The possibility to save the testicle is the fastest possible surgical intervention which is indicated by the presence of acute pain even at rest. The time element is more important to diagnose and proceed further with surgical intervention. Testicular damage is a consequence which mainly depends on the moment of onset of symptoms, at the time when the symptoms are diagnosed, the earliest action to be performed is surgical intervention. Sometimes medical tests are needed to confirm a diagnosis, or to help identify another cause for symptoms; for example, the urine test, that is used to check for infection, associated with the scrotal ultrasound test. Control of blood flow to the longitudinal supply vessels of the testicles is indicated. The sign that indicates testicular rotation is a reduction in blood flow. This is the element which is distinguished from ultrasound examination. Surgery may be needed to determine if the patient’s symptoms are caused by the rotation of the testis or any other condition. Discussion: As a surgical intervention of the emergency, the torsion of the test depends very much on the duration of the torsion, as the success in the life of the testicle depends on the fastest surgical intervention. From the previous clinic, it is noted that in any case presented to the pediatric patient diagnosed with testicular rotation, there is always a link with personal history that the patient refers to the presence of a previous episode of testicular trauma. Literature supports this fact very logically. Conclusions: Salvation without testicular atrophy depends closely on establishing the diagnosis of testicular rotation as soon as possible. Following the logic above, it can be said that the diagnosis for rotation should be performed as soon as possible, to avoid consequences that will not be favorable for the patient.Keywords: acute scrotum, test torsion, newborns, clinical presentation
Procedia PDF Downloads 150436 Emotional, Behavioral and Social Problems in Children with Fecal Incontinence by Child Behavior Checklist (CBCL): A Cross-sectional Study
Authors: Roshanak Farjad, Amirhossein Hosseini
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Fecal incontinence (FI) is a stressful condition for children and their parents that may affect the patient’s psychological well-being. Evaluating the patients’ psychological status may help physicians manage the disease effectively. This study aimed to assess the emotional and behavioral disturbances in children with FI who were referred to the pediatric gastroenterology clinic in Mofid Children’s Hospital from April 2021 to 2022. This cross-sectional study included children (over four years old) with chronic constipation and fecal incontinence. The diagnosis of chronic constipation and FI were made according to Rome-IV criteria. The Child Behavior Checklist (CBCL) evaluated patients’ emotional, behavioral, and social problems. One hundred one patients with a mean age of 7.96 years were enrolled in the study; 67.32% were males. According to CBCL, 12% (12 patients) indicated emotional and behavioral problems, with CBCL scores in the clinical or at-risk range. We detected anxious/depressed problems in five (4.95%), withdrawn/depressed problems in eight (7.92%), somatic complaints in seven (6.93%), social problems in eight (7.92%), thought problems in nine (8.91%), attention problems in seven (6.93%), rule-breaking behavior in two (1.98%), and aggressive behavior in nine (8.91%) patients. The risk of internalizing and externalizing disorders was reported in four (3.96%) and five (4.95%) patients. Also, eight (7.92%) and seven (6.93%) patients had clinical symptoms of internalizing and externalizing disorders, respectively. There was no significant relationship between patients’ age and gender with the CBCL scores in any subscales. However, there was a significant difference in the total score among the age groups (P = 0.04). The relatively high prevalence of emotional, behavioral, and social problems in our study corroborates the importance of psychological screening of children with FI during the treatment process.Keywords: chronic constipation, child behavior checklist (CBCL), fecal incontinence, rome-IV criteria
Procedia PDF Downloads 74435 An Exploratory Study on Newborns Using Massage Oil to Induce Miliaria
Authors: Chia-Feng Chen, Wan-Yi Lin, Chia-En Liu
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Background: There are approximately 600 newborns that stay four weeks in our postpartum agency every year. As we all know, newborn’s skin is 40-60% thinner than adult skin, newborn skin has a higher trans epidermal water loss, so many postpartum agencies use massage oil every day, no matter which seasons. In fact, neonatal miliaria or prickly heat is the most common condition from two to three -week- old newborns. According to research, about 80 percent of two to three -week- old baby are diagnosed with prickly heat because nurses apply massage oil to their faces every day. In China, we can use honeysuckle to wipe the newborn's face for treatment. Purpose: the purpose of the study is to discuss that using massage oil will be induced neonatal miliaria among two or three-week-old newborns and the aim of the study is to assess the protocol of miliaria condition with the face. Methods: a quasi-experimental design was used to evaluated the result between massage oil and non massage oil. A total of 22 participants were recruited randomly and analyzed from August to September in the south of China and collected for about 2 week long. The 22 participants were randomly selected and live in the stable air condition belong, 24 to 26℃. Results: the 64% of participants were diagnosed with miliaria using massage oil, the 2/8 of participants were diagnosed with miliaria no using massage oil. The pearson correction was0.67. The result of 22 participants, including massage oil, and diagnosed with miliaris. Besides, in our study, 9 of participants with miliaria for 3 to 6 days on the face, were treatment with honey-suckle wipe 3days through pediatric doctor suggestion. The effect of honey-suckle were useful in improving miliaria and decreasing the anxiety of parents. Conclusions: Miliaria is a common condition in newborns, especially in summer. The authors postulate that the massage oil did not find suitable for newborn in summer, and the study provides evidence that honey-suckle effectively control miliaria on using massage oil of participants.Keywords: massage oil, miliaria, newborn, honey suckle
Procedia PDF Downloads 83434 Role of Natural Products in Drug Discovery of Anti-Biotic and Anti-Cancer Agents
Authors: Sunil Kumar
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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues
Procedia PDF Downloads 152433 Evaluation of the Role of Circulating Long Non-Coding RNA H19 as a Promising Biomarker in Plasma of Patients with Gastric Cancer
Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr
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Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.Keywords: biomarker, gastric, cancer, LncRNA
Procedia PDF Downloads 318432 Mannequin Evaluation of 3D-Printed Intermittent Oro-Esophageal Tube Guide for Dysphagia
Authors: Yujin Jeong, Youkyung Son, Myounghwan Choi, Sanghyub Lee, Sangyeol Lee, Changho Hwang, Kyo-in Koo
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Dysphasia is difficulty in swallowing food because of oral cavity impairments induced by stroke, muscle damage, tumor. Intermittent oro-esophageal (IOE) tube feeding is one of the well-known feeding methods for the dysphasia patients. However, it is hard to insert at the proper position in esophagus. In this study, we design and fabricate the IOE tube guide using 3-dimensional (3D) printer. The printed IOE tube is tested in a mannequin (Airway Management Trainer, Co., Ltd., Copenhagen, Denmark) mimicking human’s esophagus. The gag reflex point is measured as the design point in the mannequin. To avoid the gag reflex, we design various shapes of IOE tube guide. One structure is separated into three parts; biting part, part through oral cavity, connecting part to oro-esophageal. We designed 6 types of IOE tube guide adjusting length and angle of these three parts. To evaluate the IOE tube guide, it is inserted in the mannequin, and through the inserted guide, an endoscopic camera successfully arrived at the oro-esophageal. We had planned to apply this mannequin-based design experience to patients in near future.Keywords: dysphagia, feeding method, IOE tube guide, 3-D printer
Procedia PDF Downloads 434431 Biosurfactant-Mediated Nanoparticle Synthesis by Bacillus subtilis
Authors: Satya Eswari Jujjavarapu, Swasti Dhagat, Lata Upadhyay, Reecha Sahu
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Silver nanoparticles have a broad range of antimicrobial and antifungal properties ranging from soaps, pastes to sterilization and drug delivery systems. These can be synthesized by physical, chemical and biological methods; biological methods being the most popular owing to their non-toxic nature and reduced energy requirements. Microbial surfactants, produced on the microbial cell surface or excreted extracellularly are an alternative to synthetic surfactants for the production of silver nanoparticles. Hence, they are also called as green molecules. Microbial lipopeptide surfactants (biosurfactant) exhibit anti-tumor and anti-microbial properties and can be used as drug delivery agents. In this study, biosurfactant was synthesized by using a strain of acillus subtilis. The biosurfactant thus produced was analysed by emulsification assay, oil spilling test, and haemolytic test. Biosurfactant-mediated silver nanoparticles were synthesised by microwave irradiation of the culture supernatant and further characterized by UV–vis spectroscopy for a range of 400-600 nm. The UV–vis spectra showed a surface plasmon resonance vibration band at 410 nm corresponding to the peak of silver nanoparticles.Keywords: biosurfactant, Bacillus subtilis, silver nano particle, lipopeptide
Procedia PDF Downloads 239430 Cloning and Expression of Azurin: A Protein Having Antitumor and Cell Penetrating Ability
Authors: Mohsina Akhter
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Cancer has become a wide spread disease around the globe and takes many lives every year. Different treatments are being practiced but all have potential side effects with somewhat less specificity towards target sites. Pseudomonas aeruginosa is known to secrete a protein azurin with special anti-cancer function. It has unique cell penetrating peptide comprising of 18 amino acids that have ability to enter cancer cells specifically. Reported function of Azurin is to stabilize p53 inside the tumor cells and induces apoptosis through Bax mediated cytochrome c release from mitochondria. At laboratory scale, we have made recombinant azurin through cloning rpTZ57R/T-azu vector into E.coli strain DH-5α and subcloning rpET28-azu vector into E.coli BL21-CodonPlus (DE3). High expression was ensured with IPTG induction at different concentrations then optimized high expression level at 1mM concentration of IPTG for 5 hours. Purification has been done by using Ni+2 affinity chromatography. We have concluded that azurin can be a remarkable improvement in cancer therapeutics if it produces on a large scale. Azurin does not enter into the normal cells so it will prove a safe and secure treatment for patients and prevent them from hazardous anomalies.Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics
Procedia PDF Downloads 311429 Aristotle University of Thessaloniki
Authors: Ail Akbar Emamverdian, Neriman Özada, Atabak Rahimzadeh Ilkhchi, Zahra Emamverdian
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The reverse shoulder prosthesis is an innovative procedure design to treat of (GH) joint problems with severe rotator cuff deficiency. The original reverse shoulder prosthesis was invented by France surgery in1985 and has been in clinical use in the United States in 2004. These prostheses consist of baseplate that attached to the glenoid, in order to hold a spherical component, and humeral part consist of polyethylene insert which is flat. This prosthesis is the ‘reverse’ configuration. The indications for the reverse prosthesis are: (1) treating failed hemi arthroplasty with irrecoverable rotator cuff tears, (2) relief of painful arthritis associated with cuff tear arthropathy, (3) instauration after tumor resection, (4) pseudo paralysis because of irrecoverable rotator cuff tears (5) some fractures of the shoulder which reverse shoulder prostheses is only the option for treatment. This prosthesis resulting in relief of pain and decreasing the range of motion in above indications. However, this prosthesis and its applications such as notching of the scapula, dislocation of the prosthesis parts and acromial stress fractures. In this article the reverse shoulder prostheses, indication has been reviewed. This study can make clear aspect of reverse shoulder prosthesis that can help to find some solution in future.Keywords: prostheses, complications, reverse shoulder prosthesis, indications
Procedia PDF Downloads 278428 2-Thioimidazole Analogues: Synthesis, in silico Studies and in vitro Anticancer and Antiprotozoal Evaluation
Authors: Drashti G. Daraji, Rosa E. Moo-Puc, Hitesh D. Patel
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Substituted 2-Thioimidazole analogues have been synthesized and confirmed by advanced spectroscopic techniques. Among them, ten compounds have been selected and evaluated for their in vitro anti-cancer activity at the National Cancer Institute (NCI) for testing against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types. Furthermore, synthesized compounds were tested for their in vitro antiprotozoal activity, and none of them exhibited significant potency against antiprotozoans. It was observed that the tested all compounds seem effective on the UACC-62 melanoma cancer cell line as compared to other cancer cell lines and also exhibited the least potent in the Non-Small Cell Lung Cancer cell line in one-dose screening. In silico studies of these derivatives were carried out by molecular docking techniques and Absorption, Distribution, Metabolism, and Excretion (ADME) using Schrödinger software to find potent B-Raf kinase inhibitor (PDB ID: 3OG7). All the compounds have been performed for docking study; Compound D4 has a good docking score for melanoma cancer as compared with other.Keywords: anticancer activity, cancer cell line, 2-thio imidazole, one-dose assay, molecular docking
Procedia PDF Downloads 143427 Small Molecule Inhibitors of PD1-PDL1 Interaction
Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak
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Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.Keywords: PD1, PDL1, cancer, small molecule, drug discovery
Procedia PDF Downloads 394