Search results for: drug therapy problem
8954 Comparison of Titanium and Aluminum Functions as Spoilers for Dose Uniformity Achievement in Abutting Oblique Electron Fields: A Monte Carlo Simulation Study
Authors: Faranak Felfeliyan, Parvaneh Shokrani, Maryam Atarod
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Introduction Using electron beam is widespread in radiotherapy. The main criteria in radiation therapy is to irradiate the tumor volume with maximum prescribed dose and minimum dose to vital organs around it. Using abutting fields is common in radiotherapy. The main problem in using abutting fields is dose inhomogeneity in the junction region. Electron beam divergence and lateral scattering may lead to hot and cold spots in the junction region. One solution for this problem is using of a spoiler to broaden the penumbra and uniform dose in the junction region. The goal of this research was to compare titanium and aluminum effects as a spoiler for dose uniformity achievement in the junction region of oblique electron fields with Monte Carlo simulation. Dose uniformity in the junction region depends on density, scattering power, thickness of the spoiler and the angle between two fields. Materials and Methods In this study, Monte Carlo model of Siemens Primus linear accelerator was simulated for a 5 MeV nominal energy electron beam using manufacture provided specifications. BEAMnrc and EGSnrc user code were used to simulate the treatment head in electron mode (simulation of beam model). The resulting phase space file was used as a source for dose calculations for 10×10 cm2 field size at SSD=100 cm in a 30×30×45 cm3 water phantom using DOSXYZnrc user code (dose calculations). An automatic MP3-M water phantom tank, MEPHYSTO mc2 software platform and a Semi-Flex Chamber-31010 with sensitive volume of 0.125 cm3 (PTW, Freiburg, Germany) were used for dose distribution measurements. Moreover, the electron field size was 10×10 cm2 and SSD=100 cm. Validation of developed beam model was done by comparing the measured and calculated depth and lateral dose distributions (verification of electron beam model). Simulation of spoilers (using SLAB component module) placed at the end of the electron applicator, was done using previously validated phase space file for a 5 MeV nominal energy and 10×10 cm2 field size (simulation of spoiler). An in-house routine was developed in order to calculate the combined isodose curves resulting from the two simulated abutting fields (calculation of dose distribution in abutting electron fields). Results Verification of the developed 5.9 MeV electron beam model was done by comparing the calculated and measured dose distributions. The maximum percentage difference between calculated and measured PDD was 1%, except for the build-up region in which the difference was 2%. The difference between calculated and measured profile was 2% at the edges of the field and less than 1% in other regions. The effect of PMMA, aluminum, titanium and chromium in dose uniformity achievement in abutting normal electron fields with equivalent thicknesses to 5mm PMMA was evaluated. Comparing R90 and uniformity index of different materials, aluminum was chosen as the optimum spoiler. Titanium has the maximum surface dose. Thus, aluminum and titanium had been chosen to use for dose uniformity achievement in oblique electron fields. Using the optimum beam spoiler, junction dose decreased from 160% to 110% for 15 degrees, from 180% to 120% for 30 degrees, from 160% to 120% for 45 degrees and from 180% to 100% for 60 degrees oblique abutting fields. Using Titanium spoiler, junction dose decreased from 160% to 120% for 15 degrees, 180% to 120% for 30 degrees, 160% to 120% for 45 degrees and 180% to 110% for 60 degrees. In addition, penumbra width for 15 degrees, without spoiler in the surface was 10 mm and was increased to 15.5 mm with titanium spoiler. For 30 degrees, from 9 mm to 15 mm, for 45 degrees from 4 mm to 6 mm and for 60 degrees, from 5 mm to 8 mm. Conclusion Using spoilers, penumbra width at the surface increased, size and depth of hot spots was decreased and dose homogeneity improved at the junction of abutting electron fields. Dose at the junction region of abutting oblique fields was improved significantly by using spoiler. Maximum dose at the junction region for 15⁰, 30⁰, 45⁰ and 60⁰ was decreased about 40%, 60%, 40% and 70% respectively for Titanium and about 50%, 60%, 40% and 80% for Aluminum. Considering significantly decrease in maximum dose using titanium spoiler, unfortunately, dose distribution in the junction region was not decreased less than 110%.Keywords: abutting fields, electron beam, radiation therapy, spoilers
Procedia PDF Downloads 1768953 Assessing the Clinicians’ Perspectives on Formulation with Minoxidil, Finasteride, and Capixyl™ in Androgenetic Alopecia: A Nationwide Dermatologist Survey
Authors: Sharma Aseem, Dhurat Rachita, Pawar Varsha, Khalse Manisha
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Introduction: Androgenetic alopecia (AGA) is a prevalent condition characterized by progressive hair thinning driven by genetic and androgen-related factors. The current FDA-approved treatments include oral finasteride and topical minoxidil, though many patients seek combination therapies to enhance results. This study aims to evaluate the effectiveness of a combination therapy involving Minoxidil, Finasteride, and Capixyl™ based on feedback from dermatologists. Methodology: A survey, validated by experts, was distributed to 29 leading dermatologists across India (in Tier 1 and 2 cities). The survey examined real-world clinical experiences, focusing on patient outcomes and the overall effectiveness of the mentioned formulation. Results: Among the surveyed dermatologists, 41.4% identified women aged 35-40 as the most frequently diagnosed with female pattern hair loss. The combination therapy with Minoxidil, Finasteride, and Capixyl™ was utilized by 34.5% of dermatologists for over 60 patients per month. The majority highlighted the benefits of this combination therapy, which acts via multiple mechanisms, such as vasodilation and dihydrotestosterone (DHT) receptor blockade, resulting in improved hair regrowth. Additionally, patients demonstrated better clinical outcomes, enhanced compliance, and fewer side effects. Demographically, younger patients, particularly those with AGA for less than 10 years, responded more positively to the treatment. Early intervention led to quicker and more significant results. Overall satisfaction among dermatologists was high, with 86.2% expressing positive feedback on the therapy. In terms of treatment outcomes, 51.7% of dermatologists observed visible results within 4-6 months, while 34.5% noticed a significant reduction in hair fall within 8-12 weeks. Improvements in scalp health were reported by 48.3%, and 51.7% saw an increased hair density within 3-4 months. Despite mild side effects such as scalp irritation, dryness, flaking, and occasional issues like folliculitis, headaches, itching, and redness, patient satisfaction remained high. Dermatologists reported that 93.1% of patients experienced faster and better hair regrowth with Capixyl™ compared to Minoxidil alone. Suggestions for improving the formulation included incorporating peptides like Saw Palmetto and enhancing product packaging to better meet patient needs. Discussion: The combination of Minoxidil, Finasteride, and Capixyl™ yielded positive clinical outcomes, especially in improving hair density, scalp health, and overall patient satisfaction. Dermatologists found that Capixyl™ peptides enhanced the therapeutic effect, promoting hair regrowth and improving compliance. While side effects were generally mild, there were suggestions to further improve the formulation by adding additional peptides like Saw Palmetto. Conclusion: The combination of Minoxidil and Finasteride fortified with Capixyl™ presents a promising therapeutic option for managing AGA. Dermatologists reported significant improvements in hair density, scalp health, and patient satisfaction. With its favorable efficacy and manageable side effects, this formulation proves to be a valuable addition to the treatment landscape for AGA.Keywords: androgenetic alopecia, combination therapy, minoxidil, finasteride, capixyl
Procedia PDF Downloads 168952 Optimization Approach to Estimate Hammerstein–Wiener Nonlinear Blocks in Presence of Noise and Disturbance
Authors: Leili Esmaeilani, Jafar Ghaisari, Mohsen Ahmadian
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Hammerstein–Wiener model is a block-oriented model where a linear dynamic system is surrounded by two static nonlinearities at its input and output and could be used to model various processes. This paper contains an optimization approach method for analysing the problem of Hammerstein–Wiener systems identification. The method relies on reformulate the identification problem; solve it as constraint quadratic problem and analysing its solutions. During the formulation of the problem, effects of adding noise to both input and output signals of nonlinear blocks and disturbance to linear block, in the emerged equations are discussed. Additionally, the possible parametric form of matrix operations to reduce the equation size is presented. To analyse the possible solutions to the mentioned system of equations, a method to reduce the difference between the number of equations and number of unknown variables by formulate and importing existing knowledge about nonlinear functions is presented. Obtained equations are applied to an instance H–W system to validate the results and illustrate the proposed method.Keywords: identification, Hammerstein-Wiener, optimization, quantization
Procedia PDF Downloads 2578951 Energy Deposited by Secondary Electrons Generated by Swift Proton Beams through Polymethylmethacrylate
Authors: Maurizio Dapor, Isabel Abril, Pablo de Vera, Rafael Garcia-Molina
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The ionization yield of ion tracks in polymers and bio-molecular systems reaches a maximum, known as the Bragg peak, close to the end of the ion trajectories. Along the path of the ions through the materials, many electrons are generated, which produce a cascade of further ionizations and, consequently, a shower of secondary electrons. Among these, very low energy secondary electrons can produce damage in the biomolecules by dissociative electron attachment. This work deals with the calculation of the energy distribution of electrons produced by protons in a sample of polymethylmethacrylate (PMMA), a material that is used as a phantom for living tissues in hadron therapy. PMMA is also of relevance for microelectronics in CMOS technologies and as a photoresist mask in electron beam lithography. We present a Monte Carlo code that, starting from a realistic description of the energy distribution of the electrons ejected by protons moving through PMMA, simulates the entire cascade of generated secondary electrons. By following in detail the motion of all these electrons, we find the radial distribution of the energy that they deposit in PMMA for several initial proton energies characteristic of the Bragg peak.Keywords: Monte Carlo method, secondary electrons, energetic ions, ion-beam cancer therapy, ionization cross section, polymethylmethacrylate, proton beams, secondary electrons, radial energy distribution
Procedia PDF Downloads 2878950 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats
Authors: Prerna Kalra, Surender Singh
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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity
Procedia PDF Downloads 2928949 Sexual Health and Sexual Risk Behavior of the Youth with HIV Positive in Northeastern Part, Thailand
Authors: Orathai Srithongtham, Ubonsri Thabuddha
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The youth with HIV positive is not difference from the general youth in term of sexual needs. Sexual health is crucial the most to support the youth with HIV positive to be sexual well-being. This study aims to elucidate the sexual health on protection from STDs (Sexual Transmitted Diseases) and HIV transmission and to explain sexual risk behavior of the youth with HIV positive. The target group was the youth with HIV positive about 23 cases from two provinces in northeastern part of Thailand. Qualitative method was applied for collecting data by in-depth interview. Content analysis was use for data analysis. The youth with HIV positive was protection from STDs and HIV transmission by using the condom during sexual activity. The reason to deny the condom use were ashamed, condom is not a part of life, no have fit size, and the youth fear to stigmatized as a mental disorder and fear to stigmatized as going to fuck someone. The youth who trust with nurse in clinic was dare to request the condom by face. Sexual activity without condom use is sexual risk behavior. The major causes were couple trust and the sexual enjoyment first and sexual active competition with friend without condom use. The concern on HIV was the boyfriend or girlfriend not accepts the HIV positive people, worry about the HIV transmutation, and finally not compliance to ARV drug. The youth with HIV positive was lacking of the knowledge on sexual health on the issues of access to condom and the concern to keep on relationship with the boyfriend or girlfriend. This concern issues was led to the non-adherence of ARV drug and HIV distribution. To provide the sexual health service is more essential to the youth with HIV positive.Keywords: sexual health, sexual risk behavior, youth, HIV
Procedia PDF Downloads 4788948 Multi-Criteria Evaluation for the Selection Process of a Wind Power Plant's Location Using Choquet Integral
Authors: Serhat Tüzün, Tufan Demirel
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The objective of the present study is to select the most suitable location for a wind power plant station through Choquet integral method. The problem of selecting the location for a wind power station was considered as a multi-criteria decision-making problem. The essential and sub-criteria were specified and location selection was expressed in a hierarchic structure. Among the main criteria taken into account in this paper are wind potential, technical factors, social factors, transportation, and costs. The problem was solved by using different approaches of Choquet integral and the best location for a wind power station was determined. Then, the priority weights obtained from different Choquet integral approaches are compared and commented on.Keywords: multi-criteria decision making, choquet integral, fuzzy sets, location of a wind power plant
Procedia PDF Downloads 4138947 Accelerated Molecular Simulation: A Convolution Approach
Authors: Jannes Quer, Amir Niknejad, Marcus Weber
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Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling
Procedia PDF Downloads 3298946 The Pharmacogenetics of Type 1 Cannabinoid Receptor (CB1) Gene Associated with Adverse Drug Reactions in Thai Patients
Authors: Kittitara Chunlakittiphan, Patompong Satapornpong
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Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population
Procedia PDF Downloads 1028945 Isolated Iterating Fractal Independently Corresponds with Light and Foundational Quantum Problems
Authors: Blair D. Macdonald
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After nearly one hundred years of its origin, foundational quantum mechanics remains one of the greatest unexplained mysteries in physicists today. Within this time, chaos theory and its geometry, the fractal, has developed. In this paper, the propagation behaviour with an iteration of a simple fractal, the Koch Snowflake, was described and analysed. From an arbitrary observation point within the fractal set, the fractal propagates forward by oscillation—the focus of this study and retrospectively behind by exponential growth from a point beginning. It propagates a potentially infinite exponential oscillating sinusoidal wave of discrete triangle bits sharing many characteristics of light and quantum entities. The model's wave speed is potentially constant, offering insights into the perception and a direction of time where, to an observer, when travelling at the frontier of propagation, time may slow to a stop. In isolation, the fractal is a superposition of component bits where position and scale present a problem of location. In reality, this problem is experienced within fractal landscapes or fields where 'position' is only 'known' by the addition of information or markers. The quantum' measurement problem', 'uncertainty principle,' 'entanglement,' and the classical-quantum interface are addressed; these are a problem of scale invariance associated with isolated fractality. Dual forward and retrospective perspectives of the fractal model offer the opportunity for unification between quantum mechanics and cosmological mathematics, observations, and conjectures. Quantum and cosmological problems may be different aspects of the one fractal geometry.Keywords: measurement problem, observer, entanglement, unification
Procedia PDF Downloads 928944 Public Health Campaign to Eradicate Hepatitis C Virus during the Covid-19 Emergency in the North-East of Italy
Authors: Emanuela Zilli, Antonio Madia, Milvia Marchiori, Paola Anello, Chiara Cabbia, Emanuela Velo, Delia Campagnolo, Michele Scomazzon, Emanuela Salvatico, S. Tikvina, Antonio Miotti
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Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). Antiviral medicines can cure more than 95% of cases of hepatitis C infection, but access to diagnosis and treatment remains low. The ULSS 6 Euganea – Health Trust has implemented a campaign to eradicate hepatitis C in the province of Padua (North-East of Italy), which can be subdivided into three areas: North (300.000 inhabitants), Centre (400.000) and South (300.000). In September 2021, the project was launched in the Northern area; a set of brochures was distributed in outpatient services, general practitioners’ clinics and offices, community pharmacy services, social health districts, and through social networks. The Hepatology Service contacted 460 patients selected by the Clinical Laboratory (positivity for HCV antibodies): 83 patients (18.0%) had been already cured of HCV infection, missing or deceased; 377 patients (82.0%) met the criteria to be eligible for HCV eradication therapy and were therefore included in a Day Service specific agenda and followed by a multidisciplinary team of healthcare professionals, with a dedicated telephone line. Haemato-chemical tests, general medical check-ups and ultrasound tests with fibroscan were performed. Patients were tested for Sars-CoV-2 positivity; those not yet vaccinated against Covid-19 were encouraged to complete the vaccination scheme. All 377 patients (100%) received HCV eradication therapy at the community pharmacy service; a detailed explanation of how to take their medication was provided. At the end of the first phase, Covid-19 vaccination rate was 100% (377/377), including patients already vaccinated and new-vaccinated. Check-up appointments were arranged after 2 or 3 months, according to the treatment plan. The awareness campaign and the organization of HCV eradication therapy service by ULSS 6 Euganea are proving to be effective; the project is now going to be applied to Central and Southern areas of the province (1.132 patients).Keywords: public health, HCV-eradication, Covid-19 emergency, health communication strategies
Procedia PDF Downloads 1078943 Development of Wound Dressing System Based on Hydrogel Matrix Incorporated with pH-Sensitive Nanocarrier-Drug Systems
Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta
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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.
Procedia PDF Downloads 1478942 Epigenetic Drugs for Major Depressive Disorder: A Critical Appraisal of Available Studies
Authors: Aniket Kumar, Jacob Peedicayil
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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder
Procedia PDF Downloads 1898941 Efficacy and Mechanisms of Acupuncture for Depression: A Meta-Analysis of Clinical and Preclinical Evidence
Authors: Yimeng Zhang
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Major depressive disorder (MDD) is a prevalent mental health condition with a substantial economic impact and limited treatment options. Acupuncture has gained attention as a promising non-pharmacological intervention for alleviating depressive symptoms. However, its mechanisms and clinical effectiveness remain incompletely understood. This meta-analysis aims to (1) synthesize existing evidence on the mechanisms and clinical effectiveness of acupuncture for depression and (2) compare these findings with pharmacological interventions, providing insights for future research. Evidence from animal models and clinical studies indicates that acupuncture may enhance hippocampal and network neuroplasticity and reduce brain inflammation, potentially alleviating depressive disorders. Clinical studies suggest that acupuncture can effectively relieve primary depression, particularly in milder cases, and is beneficial in managing post-stroke depression, pain-related depression, and postpartum depression, both as a standalone and adjunctive treatment. Notably, combining acupuncture with antidepressant pharmacotherapy appears to enhance treatment outcomes and reduce medication side effects, addressing a critical issue in conventional drug therapy's high dropout rates. This meta-analysis, encompassing 12 studies and 710 participants, draws data from eight digital databases (PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP) covering the period from 2012 to 2022. Utilizing Stata software 15.0, the meta-analysis employed random-effects and fixed-effects models to assess the distribution of depression in Traditional Chinese Medicine (TCM). The results underscore the substantial evidence supporting acupuncture's beneficial effects on depression. However, the small sample sizes of many clinical trials raise concerns about the generalizability of the findings, indicating a need for further research to validate these outcomes and optimize acupuncture's role in treating depression.Keywords: Chinese medicine, acupuncture, depression, meta-analysis
Procedia PDF Downloads 378940 Estimating the Efficiency of a Meta-Cognitive Intervention Program to Reduce the Risk Factors of Teenage Drivers with Attention Deficit Hyperactivity Disorder While Driving
Authors: Navah Z. Ratzon, Talia Glick, Iris Manor
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Attention Deficit Hyperactivity Disorder (ADHD) is a chronic disorder that affects the sufferer’s functioning throughout life and in various spheres of activity, including driving. Difficulties in cognitive functioning and executive functions are often part and parcel of the ADHD diagnosis, and thus form a risk factor in driving. Studies examining the effectiveness of intervention programs for improving and rehabilitating driving in typical teenagers have been conducted in relatively small numbers; while studies on similar programs for teenagers with ADHD have been especially scarce. The aim of the present study has been to examine the effectiveness of a metacognitive occupational therapy intervention program for reducing risk factors in driving among teenagers with ADHD. The present study included 37 teenagers aged 17 to 19. They included 23 teenagers with ADHD divided into experimental (11) and control (12) groups; as well as 14 non-ADHD teenagers forming a second control group. All teenagers taking part in the study were examined in the Tel Aviv University driving lab, and underwent cognitive diagnoses and a driving simulator test. Every subject in the intervention group took part in 3 assessment meetings, and two metacognitive treatment meetings. The control groups took part in two assessment meetings with a follow-up meeting 3 months later. In all the study’s groups, the treatment’s effectiveness was tested by comparing monitoring results on the driving simulator at the first and second evaluations. In addition, the driving of 5 subjects from the intervention group was monitored continuously from a month prior to the start of the intervention, a month during the phase of the intervention and another month until the end of the intervention. In the ADHD control group, the driving of 4 subjects was monitored from the end of the first evaluation for a period of 3 months. The study’s findings were affected by the fact that the ADHD control group was different from the two other groups, and exhibited ADHD characteristics manifested by impaired executive functions and lower metacognitive abilities relative to their peers. The study found partial, moderate, non-significant correlations between driving skills and cognitive functions, executive functions, and perceptions and attitudes towards driving. According to the driving simulator test results and the limited sampling results of actual driving, it was found that a metacognitive occupational therapy intervention may be effective in reducing risk factors in driving among teenagers with ADHD relative to their peers with and without ADHD. In summary, the results of the present study indicate a positive direction that speaks to the viability of using a metacognitive occupational therapy intervention program for reducing risk factors in driving. A further study is required that will include a bigger number of subjects, add actual driving monitoring hours, and assign subjects randomly to the various groups.Keywords: ADHD, driving, driving monitoring, metacognitive intervention, occupational therapy, simulator, teenagers
Procedia PDF Downloads 3078939 Reclaiming the Lost Jewish Identity of a Second Generation Holocaust Survivor Raised as a Christian: The Role of Art and Art Therapy
Authors: Bambi Ward
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Children of Holocaust survivors have been described as inheriting their parents’ trauma as a result of ‘vicarious memory’. The term refers to a process whereby second generation Holocaust survivors subconsciously remember aspects of Holocaust trauma, despite not having directly experienced it. This can occur even when there has been a conspiracy of silence in which survivors chose not to discuss the Holocaust with their children. There are still people born in various parts of the world such as Poland, Hungary, other parts of Europe, USA, Canada and Australia, who have only learnt of their Jewish roots as adults. This discovery may occur during a parent’s deathbed confession, or when an adult child is sorting through the personal belongings of a deceased family member. Some Holocaust survivors chose to deny their Jewish heritage and raise their children as Christians. Reasons for this decision include the trauma experienced during the Holocaust for simply being Jewish, the existence of anti-Semitism, and the desire to protect one’s self and one’s family. Although there has been considerable literature written about the transgenerational impact of trauma on children of Holocaust survivors, there has been little scholarly investigation into the effects of a hidden Jewish identity on these children. This paper presents a case study of an adult child of Hungarian Holocaust survivors who was raised as a Christian. At the age of eight she was told about her family’s Jewish background, but her parents insisted that she keep this a secret, even if asked directly. She honoured their request until she turned forty. By that time she had started the challenging process of reclaiming her Jewish identity. The paper outlines the tension between family loyalty and individual freedom, and discusses the role that art and art therapy played in assisting the subject of the case study to reclaim her Jewish identity and commence writing a memoir about her spiritual journey. The main methodology used in this case study is creative practice-led research. Particular attention is paid to the utilisation of an autoethnographic approach. The autoethnographic tools used include reflective journals of the subject of the case study. These journals reflect on the subject’s collection of autobiographical data relating to her family history, and include memories, drawings, products of art therapy, diaries, letters, photographs, home movies, objects, and oral history interviews with her mother. The case study illustrates how art and art therapy benefitted a second generation Holocaust survivor who was brought up having to suppress her Jewish identity. The process allowed her to express subconscious thoughts and feelings about her identity and free herself from the burden of the long term secret she had been carrying. The process described may also be of assistance to other traumatised people who have been trying to break the silence and who are seeking to express themselves in a positive and healing way.Keywords: art, hidden identity, holocaust, silence
Procedia PDF Downloads 2408938 Methodology for Risk Assessment of Nitrosamine Drug Substance Related Impurities in Glipizide Antidiabetic Formulations
Authors: Ravisinh Solanki, Ravi Patel, Chhaganbhai Patel
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Purpose: The purpose of this study is to develop a methodology for the risk assessment and evaluation of nitrosamine impurities in Glipizide antidiabetic formulations. Nitroso compounds, including nitrosamines, have emerged as significant concerns in drug products, as highlighted by the ICH M7 guidelines. This study aims to identify known and potential sources of nitrosamine impurities that may contaminate Glipizide formulations and assess their presence. By determining observed or predicted levels of these impurities and comparing them with regulatory guidance, this research will contribute to ensuring the safety and quality of combination antidiabetic drug products on the market. Factors contributing to the presence of genotoxic nitrosamine contaminants in glipizide medications, such as secondary and tertiary amines, and nitroso group-complex forming molecules, will be investigated. Additionally, conditions necessary for nitrosamine formation, including the presence of nitrosating agents, and acidic environments, will be examined to enhance understanding and mitigation strategies. Method: The methodology for the study involves the implementation of the N-Nitroso Acid Precursor (NAP) test, as recommended by the WHO in 1978 and detailed in the 1980 International Agency for Research on Cancer monograph. Individual glass vials containing equivalent to 10mM quantities of Glipizide is prepared. These compounds are dissolved in an acidic environment and supplemented with 40 mM NaNO2. The resulting solutions are maintained at a temperature of 37°C for a duration of 4 hours. For the analysis of the samples, an HPLC method is employed for fit-for-purpose separation. LC resolution is achieved using a step gradient on an Agilent Eclipse Plus C18 column (4.6 X 100 mm, 3.5µ). Mobile phases A and B consist of 0.1% v/v formic acid in water and acetonitrile, respectively, following a gradient mode program. The flow rate is set at 0.6 mL/min, and the column compartment temperature is maintained at 35°C. Detection is performed using a PDA detector within the wavelength range of 190-400 nm. To determine the exact mass of formed nitrosamine drug substance related impurities (NDSRIs), the HPLC method is transferred to LC-TQ-MS/MS with the same mobile phase composition and gradient program. The injection volume is set at 5 µL, and MS analysis is conducted in Electrospray Ionization (ESI) mode within the mass range of 100−1000 Daltons. Results: The samples of NAP test were prepared according to the protocol. The samples were analyzed using HPLC and LC-TQ-MS/MS identify possible NDSRIs generated in different formulations of glipizide. It was found that the NAP test generated a various NDSRIs. The new finding, which has not been reported yet, discovered contamination of Glipizide. These NDSRIs are categorised based on the predicted carcinogenic potency and recommended its acceptable intact in medicines. The analytical method was found specific and reproducible.Keywords: NDSRI, nitrosamine impurities, antidiabetic, glipizide, LC-MS/MS
Procedia PDF Downloads 378937 Post-Traumatic Stress Disorder and Problem Alcohol Use in Women: Systematic Analysis
Authors: Neringa Bagdonaite
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Study Aims: The current study aimed to systematically analyse various research done in the area of female post-traumatic stress disorder (PTSD) and alcohol abuse, and to critically review these results on the basis of theoretical models as well as answer following questions: (I) What is the reciprocal relationship between PTSD and problem alcohol use among females; (II) What are the moderating/mediating factors of this relationship? Methods: The computer bibliographic databases Ebsco, Scopus, Springer, Web of Science, Medline, Science Direct were used to search for scientific articles. Systematic analyses sample consisted of peer-reviewed, English written articles addressing mixed gender and female PTSD and alcohol abuse issues from Jan 2012 to May 2017. Results: Total of 1011 articles were found in scientific databases related to searched keywords of which 29 met the selection criteria and were analysed. The results of longitudinal studies indicate that (I) various trauma, especially interpersonal trauma exposure in childhood is linked with increased risk of revictimization in later life and problem alcohol use; (II) revictimization in adolescence or adulthood, rather than victimization in childhood has a greater impact on the onset and progression of problematic alcohol use in adulthood. Cross-sectional and epidemiological studies also support significant relationships between female PTSD and problem alcohol use. Regards to the negative impact of alcohol use on PTSD symptoms results are yet controversial; some evidence suggests that alcohol does not exacerbate symptoms of PTSD over time, while others argue that problem alcohol use worsens PTSD symptoms and is linked to chronicity of both disorders, especially among women with previous alcohol use problems. Analysis of moderating/mediating factors of PTSD and problem alcohol use revealed, that higher motives/expectancies, specifically distress coping motives for alcohol use significantly moderates the relationship between PTSD and problematic alcohol use. Whereas negative affective states mediate relationship between symptoms of PTSD and alcohol use, but only among woman with alcohol use problems already developed. Conclusions: Interpersonal trauma experience, especially in childhood and its reappearance in lifetime is linked with PTSD symptoms and problem drinking among women. Moreover, problem alcohol use can be both a cause and a consequence of trauma and PTSD, and if used for coping it, increases the likelihood of chronicity of both disorders. In order to effectively treat both disorders, it’s worthwhile taking into account this dynamic interplay of women's PTSD symptoms and problem drinking.Keywords: female, trauma, post-traumatic stress disorder, problem alcohol use, systemic analysis
Procedia PDF Downloads 1848936 In vitro and in vivo Anticancer Activity of Nanosize Zinc Oxide Composites of Doxorubicin
Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan
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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide
Procedia PDF Downloads 4128935 Electrophoretic Changes in Testis and Liver of Mice after Exposure to Diclofenac Sodium
Authors: Deepak Mohan, Sushma Sharma, Mohammad Asif
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Diclofenac sodium being one of the most common non-steroidal anti-inflammatory drugs is normally used as painkiller and to reduce inflammation. The drug is known to alter the enzymatic activities of acid and alkaline phosphatase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminases. The drug also results in change in the concentration of proteins and lipids in the body. The present study is an attempt to study different biochemical changes electrophoretically due to administration of different doses of diclofenac (4mg/kg/body weight and 14mg/kg/body weight) on liver and testes of mice from 7-28 days of investigation. Homogenization of the tissue was done, supernatant separated was loaded in the gel and native polyacrylamide gel electrophoresis was conducted. Diclofenac administration resulted in alterations of all these biochemical parameters which were observed in native polyacrylamide gel electrophoretic studies. The severe degenerative changes as observed during later stages of the experiment showed correlation with increase or decrease in the activities of all the enzymes studied in the present investigation. Image analysis of gel in liver showed a decline of 7.4 and 5.3 % in low and high dose group after 7 days whereas a decline of 9.6 and 7.5% was registered after 28 days of investigation. Similar analysis for testis also showed an appreciable decline in the activity of alkaline phosphatase after 28 days. Gel analysis of serum was also performed to find a correlation in the enzymatic activities between the tissue and blood.Keywords: diclofenac, inflammation, polyacrylamide, phosphatase
Procedia PDF Downloads 1558934 The Effectiveness of the Recovering from Child Abuse Programme (RCAP) for the Treatment of CPTSD: A Pilot Study
Authors: Siobhan Hegarty, Michael Bloomfield, Kim Entholt, Dorothy Williams, Helen Kennerley
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Complex Post-Traumatic Stress Disorder (CPTSD) confers greater risk of poor outcomes than does Post-Traumatic Stress Disorder (PTSD). Despite this, the current treatment guidelines for CPTSD aim to reduce only the ‘core’ symptoms of re-experiencing, hyper-vigilance and avoidance, while not addressing the Disturbances of Self Organisation (DSO) symptoms that distinguish this novel diagnosis from PTSD. The Recovering from Child Abuse Programme (RCAP) is a group protocol, based on the principles of cognitive behavioural therapy (CBT). Preliminary evidence suggests the program is effective at reducing DSO symptoms. This pilot study is the first to investigate the potential effectiveness of the RCAP for the specific treatment of CPTSD. This study was conducted as a service evaluation in a secondary care, traumatic stress service. Treatment was delivered once a week, in two-hour sessions, to ten existing female CPTSD patients of the service, who had experienced sexual abuse in childhood. The programme was administered by two therapists and two additional facilitators, following the RCAP protocol manual. Symptom severity was measured before the administration of therapy and was tracked across a range of measures (International Trauma Questionnaire; Patient Health Questionnaire; Community Assessment of Psychic Experience; Work and Social Adjustment Scale) at five time points, over the course of treatment. Qualitative appraisal of the programme was gathered via weekly feedback forms and from audio-taped recordings of verbal feedback given during group sessions. Preliminary results suggest the programme causes a slight reduction in CPTSD and depressive symptom severity and preliminary qualitative analysis suggests that the RCAP is both helpful and acceptable to group members. Final results and conclusions will follow completed thematic analysis of results.Keywords: Child sexual abuse, Cognitive behavioural therapy, Complex post-traumatic stress disorder, Recovering from child abuse programme
Procedia PDF Downloads 1368933 Changing Trends in the Use of Induction Agents for General Anesthesia for Cesarean Section
Authors: Mahmoud Hassanin, Amita Gupta
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Background: During current practice, Thiopentone is not cost-effectively added to resources wastage, risk of drug error with antibiotics, short shelf life, infection risk, and risk of delay while preparing during category one cesarean section. There is no significant difference or preference to the other alternative as per current use. Aims and Objectives: Patient safety, Cost-effective use of trust resources, problem awareness, Consider improvising on the current practice. Methods: In conjunction with the local department survey results, many studies support the change. Results: More than 50%(15 from 29) are already using Propofol, more than 75% of the participant are willing to shift to Propofol if it becomes standard, and the cost analysis also revealed that Thiopentone 10 X500=£60 Propofol 10X200= £5.20, Cost of Thiopentone/year =£2190. Approximately GA in a year =35-40 could cost approximately £20 Propofol, given it is a well-established practice. We could save not only money, but it will be environmentally friendly also to avoid adding any carbon footprints. Recommendation: Thiopentone is rarely used as an induction agent for the category one Caesarean section in our obstetric emergency theatres. Most obstetric anesthetists are using Propofol. Keep both Propofol and thiopentone(powder not withdrawn) in the cat one cesarean section emergency drugs tray ready until the department completely changes the practice protocol. A further retrospective study is required to compare the outcomes for these induction agents through the local database.Keywords: thiopentone, propofol, category 1 caesarean, induction agents
Procedia PDF Downloads 1438932 Innovation in the Provision of Medical Services in the Field of Qualified Sports and Services Related to the Therapy of Metabolism Disorders and the Treatment of Obesity
Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok
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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.Keywords: innovation of medical services, sport, obesity, innovation
Procedia PDF Downloads 1288931 Multi-Institutional Report on Toxicities of Concurrent Nivolumab and Radiation Therapy
Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes
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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation
Procedia PDF Downloads 3938930 Inducible Trans-Encapsidation System for Temporal Separation of Hepatitis C Virus Life Cycle
Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu
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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.Keywords: assembly inhibitors, core protein, HCV, trans-complementation
Procedia PDF Downloads 2938929 Clarification of Taxonomic Confusions among Adulterated Drugs Coffee Seena and Seena Weed through Systematic and Pharmaceutical Markers
Authors: Shabnum Shaheen, Nida Haroon, Farah Khan, Sumera Javad, Mehreen Jalal, Samina Sarwar
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Coffee Senna is pharmaceutically very important and used for multiple health disorders such as gastric pains, indigestion, snakebites, asthma and fever, tuberculosis and menstrual problems. However, its immense medicinal value and great demand lead to adulteration issue which could be injurious for users. Some times its adulterant Seena weed (Senna occidentalis L.) is used as its substitute which definitely not as effective as Coffee Senna. Hence, the present study was undertaken to provide some tools for systematic and pharmaceutical authentication of a shrubby plant Coffee Senna (Cassia occidentalis Linn.). These parameters included macro and micro morphological characters, anatomical and palynomorph characterization, solubility, fluorescence and phytochemical analysis. By the application of these parameters acquired results revealed that, these two plants are distinct from each other. The Coffee Seena was found to be an annual shrub with trilobed pollen, diacytic, paracytic and anisocytic stomata whereas the Seena weed stands out as an annual or perennial herb with spheroidal and circular pollen and paracytic type of stomata. The powdered drug of Coffee seena is dark grayish green whereas the powdered drug of Seena weed is light green in color. These findings are constructive in authentic identification of these plants.Keywords: coffee senna, Senna weed, taxonomic evaluation, pharmaceutical markers
Procedia PDF Downloads 5168928 Proposing Problem-Based Learning as an Effective Pedagogical Technique for Social Work Education
Authors: Christine K. Fulmer
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Social work education is competency based in nature. There is an expectation that graduates of social work programs throughout the world are to be prepared to practice at a level of competence, which is beneficial to both the well-being of individuals and community. Experiential learning is one way to prepare students for competent practice. The use of Problem-Based Learning (PBL) is a form experiential education that has been successful in a number of disciplines to bridge the gap between the theoretical concepts in the classroom to the real world. PBL aligns with the constructivist theoretical approach to learning, which emphasizes the integration of new knowledge with the beliefs students already hold. In addition, the basic tenants of PBL correspond well with the practice behaviors associated with social work practice including multi-disciplinary collaboration and critical thinking. This paper makes an argument for utilizing PBL in social work education.Keywords: social work education, problem-based learning, pedagogy, experiential learning, constructivist theoretical approach
Procedia PDF Downloads 3158927 Parameter Estimation of False Dynamic EIV Model with Additive Uncertainty
Authors: Dalvinder Kaur Mangal
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For the past decade, noise corrupted output measurements have been a fundamental research problem to be investigated. On the other hand, the estimation of the parameters for linear dynamic systems when also the input is affected by noise is recognized as more difficult problem which only recently has received increasing attention. Representations where errors or measurement noises/disturbances are present on both the inputs and outputs are usually called errors-in-variables (EIV) models. These disturbances may also have additive effects which are also considered in this paper. Parameter estimation of false EIV problem using equation error, output error and iterative prefiltering identification schemes with and without additive uncertainty, when only the output observation is corrupted by noise has been dealt in this paper. The comparative study of these three schemes has also been carried out.Keywords: errors-in-variable (EIV), false EIV, equation error, output error, iterative prefiltering, Gaussian noise
Procedia PDF Downloads 4978926 A Multi-Criteria Model for Scheduling of Stochastic Single Machine Problem with Outsourcing and Solving It through Application of Chance Constrained
Authors: Homa Ghave, Parmis Shahmaleki
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This paper presents a new multi-criteria stochastic mathematical model for a single machine scheduling with outsourcing allowed. There are multiple jobs processing in batch. For each batch, all of job or a quantity of it can be outsourced. The jobs have stochastic processing time and lead time and deterministic due dates arrive randomly. Because of the stochastic inherent of processing time and lead time, we use the chance constrained programming for modeling the problem. First, the problem is formulated in form of stochastic programming and then prepared in a form of deterministic mixed integer linear programming. The objectives are considered in the model to minimize the maximum tardiness and outsourcing cost simultaneously. Several procedures have been developed to deal with the multi-criteria problem. In this paper, we utilize the concept of satisfaction functions to increases the manager’s preference. The proposed approach is tested on instances where the random variables are normally distributed.Keywords: single machine scheduling, multi-criteria mathematical model, outsourcing strategy, uncertain lead times and processing times, chance constrained programming, satisfaction function
Procedia PDF Downloads 2658925 Production of Camel Nanobodies against of Anti-Morphine-3-Glucuronide for the Development of a Biosensor for Detecting Illicit Drug
Authors: Shirin Jalili, Sadegh Hasannia, Hadi Shirzad, Afshin Khara
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Morphine is one of the most medicinally important analgesics and narcotics. Structurally, it is classified as an alkaloid because of the presence of nitrogen. Its structure is similar to that of codeine, thebaine, and heroin. An immunoassay to accurately discriminate between these analogous alkaloids would be highly beneficial. A key factor for such an assay is specificity with high sensitivity, which is totally dependent on the antibody employed. However, most antibodies against haptens are polyclonal serum antibodies that exhibit significant cross-reactivities with closely related compounds. The camel-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity, possessing unique properties compared to other conventional antibodies. In this study, a library containing the VHH genes of a camel immunized with with morphine conjugated BSA following phage display technology was generated. By screening the camel-derived variable region of the heavy chain cDNA phage display library with the ability to bind the desired hapten, we obtained some nanobodies that recognize this hapten. Phage display expression of the Nbs from this library and pannings against this hapten resulted in a clear enrichment of four distinct Nb-displaying phages with specificity for morphine that could be a potential target site for the development of new strategies for the development of a biosensor for detecting illicit drug.Keywords: phage display, nanobody, Morphine-3, glucuronide, ELISA, biosensor
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