Search results for: twin therapeutic approach
14895 Influence of Maturity Stage on Nutritional and Therapeutic Potentialities of Solanum anguivi Lam Berries (Gnagnan) Cultivated in CôTe D'Ivoire
Authors: G. Dan Chépo, L. Ban-Koffi, N. Kouassi Kouakou, M. Dje Kouakou, J. Nemlin, A. Sahore Drogba, L. Kouame Patrice
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Solanum anguivi Lam, collectively called Gnagnan in Côte d'Ivoire is an eggplant with nutritional and therapeutic potentialities more or less known. The present study was undertaken to analyze the biochemical composition of berries at the different stages of maturity. Data showed that at the first stage of maturity (green berries), fruits are rich in ascorbic acid (34.48 ± 1.7 mg / 100 g dm), phenolic compounds (956.7 ± 71.14 mg / 100 g dm), iron (467.7 ± 1.84 mg / 100 g dm), magnesium (404.6 ± 16.25 mg / 100 g dm) and potassium (404.64 ± 16.25 mg/100 g dm). However, at the last stage of maturity (red berries), fruits are rich in proteins, cellulose, total sugars, fat and potassium with the values of 22.53 ± 2 g/100 g dm, 19.12 ± 0.35 g/100 g dm, 3.7 ± 0.2 g/100 g dm, 2.65 ± 0.19 g/100 g dm and 2290.84 ± 22.24 mg / 100 g dm, respectively. The chromatography on thin layer revealed the presence of glucose, ribose, xylose, arabinose and fructose at all the maturity stages. Except for alkaloids and gallic tannins, the phytochemical sorting revealed that Gnagnan contain many pharmacological components. According to the maturity stages, orange and red berries showed a higher content in sterols and polyterpens, flavonoids and saponins. The green berries contain most of polyphenols, catechintannins and quinons. As for the yellow berries, they are rich in polyphenols and catechintannins. These data contribute to enhance clinical researches on nutritional and pharmacological properties of S. anguivi Lam.Keywords: Gnagnan, maturity stage, chemical composition, chromatography thin layer, phytochemical sorting
Procedia PDF Downloads 49714894 Targeting Calcium Dysregulation for Treatment of Dementia in Alzheimer's Disease
Authors: Huafeng Wei
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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 18214893 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease
Authors: Huafeng Wei
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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 20814892 Clinical Application of Mesenchymal Stem Cells for Cancer Therapy: A Review of Registered Clinical Trials
Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc
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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials
Procedia PDF Downloads 9214891 Therapeutic Effects of Toll Like Receptor 9 Ligand CpG-ODN on Radiation Injury
Authors: Jianming Cai
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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation
Procedia PDF Downloads 48014890 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer
Authors: Bhumika Wadhwa, Fayaz Malik
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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition
Procedia PDF Downloads 25614889 Eradication of Mental Illness through Buddhism
Authors: Deshar Bashu Dev
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In this modern age, most people in developed and developing countries are affected by mental illness. There are many mental illnesses, and their differing symptoms impact peoples’ lives in different ways. These illnesses affect the way people think and feel, as well as how they behave with others. Mental illness results from compound interactions between the mind, body, and environment. New technologies and sciences make the world a better place. These technologies are becoming smarter and are being developed every day to help make daily life easier However, people suffer from mental illness in every part of the world. The philosophy propounded by the Buddha, Buddhism, teaches that all life is connected, from the microcosm to macrocosm. In the 2,500 years that elapsed since the death of the Buddha, his disciples have spread his teachings and developed sophisticated psycho-therapeutic methodologies. We can find many examples in Buddhist texts and in the modern age where Buddhist philosophy modern science could not solve. The Noble Eightfold Path, which is one of the main philosophies of Buddhism; it eradicates hatred and ill will and cultivates good deeds, kindness, and compassion. Buddhism, as a practice of dialectic conversation and mindfulness training, is full of rich therapeutic tools that the mental health community has adopted to help people. Similarly, Buddhist meditation is very necessary; it purifies thoughts and avoids unnecessary thinking. This research aims to study different causes of mental illness; analyzes the different approaches to eradicate mental illness problems and provides conclusions and recommendations present solutions through Buddhism in this modern age.Keywords: mental illness, Buddhism, mindfulness, Buddhist practices
Procedia PDF Downloads 25314888 Pioneering Technology of Night Photo-Stimulation of the Brain Lymphatic System: Therapy of Brain Diseases during Sleep
Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths
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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.Keywords: brain diseases, brain lymphatic system, phototherapy, sleep
Procedia PDF Downloads 7214887 Rethinking Riba in an Agency Theoretic Framework: Islamic Banking and Finance beyond Sophistry
Authors: Muhammad Arsalan
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The efficiency of a financial intermediation system is assessed by its ability to achieve allocative efficiency, asset transformation, and the subsequent economic development. Islamic Banking and Finance (IBF) was conceived to serve as an alternate financial intermediation system adherent to the injunctions of Islam. A critical appraisal of the state of contemporary IBF reveals that it neither fulfills the aspirations of Islamic rhetoric nor is efficient in terms of asset transformation and economic development. This paper is an intuitive pursuit to explore the economic rationale of established principles of IBF, and the reasons of the persistent divergence of IBF being accused of ruses and sophistry. Disentangling the varying viewpoints, the underdevelopment of IBF has been attributed to misinterpretation of Riba, which has been explicated through a narrow fiqhi and legally deterministic approach. It presents a critical account of how incorrect conceptualization of the key injunction on Riba, steered flawed institutionalization of an Islamic Financial intermediation system. It also emphasizes on the wrong interpretation of the ontological and epistemological sources of Islamic Law (primarily Riba), that explains the perennial economic underdevelopment of the Muslim world. Deeming ‘a collaborative and dynamic Ijtihad’ as the elixir, this paper insists on the exigency of redefining Riba, i.e., a definition that incorporates the modern modes of economic cooperation and the contemporary financial intermediation ecosystem. Finally, Riba has been articulated in an agency theoretic framework to eschew expropriation of wealth, and assure protection of property rights, aimed at realizing the twin goals of a) Shari’ah adherence in true spirit, b) financial and economic development of the Muslim world.Keywords: agency theory, financial intermediation, Islamic banking and finance, ijtihad, economic development, Riba, information asymmetry
Procedia PDF Downloads 13914886 Leveraging Digital Transformation Initiatives and Artificial Intelligence to Optimize Readiness and Simulate Mission Performance across the Fleet
Authors: Justin Woulfe
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Siloed logistics and supply chain management systems throughout the Department of Defense (DOD) has led to disparate approaches to modeling and simulation (M&S), a lack of understanding of how one system impacts the whole, and issues with “optimal” solutions that are good for one organization but have dramatic negative impacts on another. Many different systems have evolved to try to understand and account for uncertainty and try to reduce the consequences of the unknown. As the DoD undertakes expansive digital transformation initiatives, there is an opportunity to fuse and leverage traditionally disparate data into a centrally hosted source of truth. With a streamlined process incorporating machine learning (ML) and artificial intelligence (AI), advanced M&S will enable informed decisions guiding program success via optimized operational readiness and improved mission success. One of the current challenges is to leverage the terabytes of data generated by monitored systems to provide actionable information for all levels of users. The implementation of a cloud-based application analyzing data transactions, learning and predicting future states from current and past states in real-time, and communicating those anticipated states is an appropriate solution for the purposes of reduced latency and improved confidence in decisions. Decisions made from an ML and AI application combined with advanced optimization algorithms will improve the mission success and performance of systems, which will improve the overall cost and effectiveness of any program. The Systecon team constructs and employs model-based simulations, cutting across traditional silos of data, aggregating maintenance, and supply data, incorporating sensor information, and applying optimization and simulation methods to an as-maintained digital twin with the ability to aggregate results across a system’s lifecycle and across logical and operational groupings of systems. This coupling of data throughout the enterprise enables tactical, operational, and strategic decision support, detachable and deployable logistics services, and configuration-based automated distribution of digital technical and product data to enhance supply and logistics operations. As a complete solution, this approach significantly reduces program risk by allowing flexible configuration of data, data relationships, business process workflows, and early test and evaluation, especially budget trade-off analyses. A true capability to tie resources (dollars) to weapon system readiness in alignment with the real-world scenarios a warfighter may experience has been an objective yet to be realized to date. By developing and solidifying an organic capability to directly relate dollars to readiness and to inform the digital twin, the decision-maker is now empowered through valuable insight and traceability. This type of educated decision-making provides an advantage over the adversaries who struggle with maintaining system readiness at an affordable cost. The M&S capability developed allows program managers to independently evaluate system design and support decisions by quantifying their impact on operational availability and operations and support cost resulting in the ability to simultaneously optimize readiness and cost. This will allow the stakeholders to make data-driven decisions when trading cost and readiness throughout the life of the program. Finally, sponsors are available to validate product deliverables with efficiency and much higher accuracy than in previous years.Keywords: artificial intelligence, digital transformation, machine learning, predictive analytics
Procedia PDF Downloads 16014885 The Improved Therapeutic Effect of Trans-Cinnamaldehyde on Adipose-Derived Stem Cells without Chemical Induction
Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou
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Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis
Procedia PDF Downloads 25814884 Investigation of FoxM1 Gene Expression in Breast Cancer and Its Relationship with miR-216B-5p Expression Level
Authors: Ramin Mehdiabadi
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Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.Keywords: breast cancer, gene expression, FoxM1, microRNA
Procedia PDF Downloads 5314883 Trigonella foenum-graecum Seeds Extract as Therapeutic Candidate for Treatment of Alzheimer's Disease
Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda
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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice
Procedia PDF Downloads 14714882 Improved Approach to the Treatment of Resistant Breast Cancer
Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova
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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy
Procedia PDF Downloads 27414881 Evaluating the Efficacy of Tasquinimod in Covid-19
Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore
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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod
Procedia PDF Downloads 19514880 Nutritionists' Perspective on the Conception of a Telenutrition Platform for Diabetes Care: Qualitative Study
Authors: Choumous Mannoubi, Dahlia Kairy, Brigitte Vachon
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The use of technology allows clinicians to provide an individualized approach in a cost-effective manner and to reach a broader client base more easily. Such interventions can be effective in ensuring self-management and follow-up of people with diabetes, reducing the risk of complications by improving accessibility to care services, and better adherence to health recommendations. Consideration of users' opinions and fears to inform the design and implementation stages of these telehealth services seems to be essential to improve their acceptance and usability. The objective of this study is to describe the telepractice of nutritionists supporting the therapeutic management of diabetic patients and document the functional requirements of nutritionists for the design of a tele-nutrition platform. To best identify the requirements and constraints of nutritionists, we conducted individual semi-structured interviews with 10 nutritionists who offered tele-nutrition services. Using a qualitative design with a descriptive approach based on the Nutrition Care Process Model (mNCP) framework, we explored in depth the state of nutritionists' telepractice in public and private health care settings, as well as their requirements for teleconsultation. Qualitative analyses revealed that nutritionists primarily used telephone calls during the COVID 19 pandemic to provide teleconsultations. Nutritionists identified the following important features for the design of a tele-nutrition platform: it should support interprofessional collaboration, allow for the development and monitoring of a care plan, integrate with the existing IT environment, be easy to use, accommodate different levels of patient literacy, and allow for easy sharing of educational materials to support nutrition education.Keywords: telehealth, nutrition, diabetes, telenutrition, teleconsultation, telemonitoring
Procedia PDF Downloads 13314879 Unusual Presentation of Colorectal Cancer within Inguinal Hernia: A Systemic Review of Reported Cases
Authors: Sena Park
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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach
Procedia PDF Downloads 10114878 Cell Line Screens Identify Biomarkers of Drug Sensitivity in GLIOMA Cancer
Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail
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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator
Procedia PDF Downloads 40914877 Avoidant Restrictive Food Intake Disorder and Its Impact on Other Eating Disorders
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Avoidant Restrictive Food Intake Disorder (ARFID) was included for the first time in DSM-5, replacing the old diagnosis of DSM-4 'Early Childhood Eating Disorder'. An ARFID is characterized by a restrictive/avoidant eating pattern that can lead to severe nutritional deficiency, weight loss, nutritional supplementation dependence, and poor psychosocial functioning. This eating pattern is associated with decreased interest in food, worries about food characteristics or the act of ingestion, and lack of concern with weight or body image. This paper aims to understand the impact of this new diagnosis in other Eating Disorders (ED) prevalence, as well as to compare their therapeutic approaches. Methodology: Literature reviewed by PubMed with the following keywords: 'ARFID', 'Prevalence', and 'Eating Disorders'. We selected articles related to this theme, written since 2016. Results: In a population of children hospitalized with ED, 5% to 14% was diagnosed with ARFID, and, as outpatient treatment, the prevalence was 22%. People diagnosed with ARFID have more prevalence of other comorbidities, especially autism spectrum, are younger, and are more often male. Regarding the treatment of ARFID, it most often required nasogastric feeding, and with less suffering associated with this procedure, compared to AN. Despite these differences, 12% of patients diagnosed with ARFID transited to AN during treatment, suggesting that the first pathology may be a risk factor for the development of AN. Conclusions: The differences identified between ARFID and the other EDs are important when analyzed as differential diagnostic hypotheses and therapeutic approaches. Further study is necessary regarding its prevalence, risk factors, and treatment.Keywords: avoidant restrictive food intake disorder, ARFID, differential diagnoses, eating disorders, prevalence
Procedia PDF Downloads 11114876 Silver Nanoparticles Loaded Cellulose Nanofibers (Cnf)/mesoporous Bioactive Glass Hydrogels For Periodontitis Treatment
Authors: Anika Pallapothu
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Periodontitis, a severe gum disease, poses a significant threat to the integrity of bone and soft tissues supporting teeth, primarily initiated by bacterial accumulation around the gum line. Conventional treatments like scaling/root planning and plaque removal are widely employed, but integrating modern technologies such as nanotechnology holds promise for innovative therapeutic approaches. This study explores the utilization of silver nanoparticles encapsulated within cellulose nanofiber (CNF) and mesoporous bioactive glass hydrogel matrices for periodontitis management. Silver nanoparticles exhibit potent antimicrobial properties by disrupting microbial cell membranes, inducing reactive oxygen species (ROS) generation, and interfering with vital cellular processes like ATP production and nucleic acid synthesis. Mesoporous bioactive glass, renowned for its high surface area, osteoconductive, and bioactivity, presents a favorable platform for pharmaceutical applications. Incorporating CNF enhances the properties of the hydrogel due to its biocompatibility, biodegradability, and water absorption capacity. The proposed composite material is anticipated to exert beneficial effects in periodontitis treatment by demonstrating antibacterial and anti-inflammatory activities, offering a promising avenue for future therapeutic interventions.Keywords: periodontitis, cellulose nanofibers, silver nanoparticles, mesoporous bioactive glass, antibacterial activity, anti-inflammatory activity
Procedia PDF Downloads 5214875 Training Program for Kindergarden Teachers on Learning through Project Approach
Authors: Dian Hartiningsih, Miranda Diponegoro, Evita Eddie Singgih
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In facing the 21st century, children need to be prepared in reaching their optimum development level which encompasses all aspect of growth and to achieve the learning goals which include not only knowledge and skill, but also disposition and feeling. Teachers as the forefront of education need to be equipped with the understanding and skill of a learning method which can prepare the children to face this 21st century challenge. Project approach is an approach which utilizes active learning which is beneficial for the children. Subject to this research are kindergarten teachers at Dwi Matra Kindergarten and Kirana Preschool. This research is a quantitative research using before and after study design. The result suggest that through preliminary training program on learning with project approach, the kindergarten teachers ability to explain project approach including understanding, benefit and stages of project approach have increased significantly, the teachers ability to design learning with project approach have also improved significantly. The result of learning design that the teachers had made shows a remarkable result for the first stage of the project approach; however the second and third design result was not as optimal. Challenges faced in the research will be elaborated further in the research discussion.Keywords: project approach, teacher training, learning method, kindergarten
Procedia PDF Downloads 33114874 Elaboration of Composites with Thermoplastic Matrix Polypropylene Charged by the Polyaniline Synthesized by the Self-Curling Method
Authors: Selma Saadia, Nacira Naar, Ahmed Benaboura
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This work is dedicated to the elaboration of composites (PP/PANI) with Polypropylene (PP) as thermoplastic polymer and the polyaniline (PANI) as electric charge doped with sulfanilic acid (PANI-As). These realized formulations are intended for the antistatic domain. The used conductive polymer is synthesized by the method self-curling which proved the obtaining of the nanoparticles of PANI in regular morphological forms. The PANI and PP composites are fabricated into a film by a twin-screw extruding. Several methods of characterization are proposed: spectroscopic, thermal, and electric. The realized composites proved a pseudo-homogeneous aspect and the threshold percolation study, showed that the formulation with 7% of PANI presents a better formulation which can be used in the antistatic domain.Keywords: extruding, PANI, Polypropylene, sulfanilic acid, self-Curling
Procedia PDF Downloads 24414873 Targetting T6SS of Klebsiella pneumoniae for Assessment of Immune Response in Mice for Therapeutic Lead Development
Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri
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Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG
Procedia PDF Downloads 10214872 Ionic Liquids-Polymer Nanoparticle Systems as Breakthrough Tools to Improve the Leprosy Treatment
Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida
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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility
Procedia PDF Downloads 15014871 Hydrotherapy with Dual Sensory Impairment (Dsi)-Deaf and Blind
Authors: M. Warburton
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Background: Case study examining hydrotherapy for a person with DSI. A 46 year-old lady completely deaf and blind post congenital rubella syndrome. Touch becomes the primary information gathering sense to optimise function in life. Communication is achieved via tactile finger spelling and signals onto her hand and skin. Hydrotherapy may provide a suitable mobility environment and somato-sensory input to people, and especially DSI persons. Buoyancy, warmth, hydrostatic pressure, viscosity and turbulence are elements of hydrotherapy that may offer a DSI person somato-sensory input to stimulate the mechanoreceptors, thermoreceptors and proprioceptors and offer a unique hydro-therapeutic environment. Purpose: The purpose of this case study was to establish what measurable benefits could be achieved from hydrotherapy with a DSI person. Methods: Hydrotherapy was provided for 8-weeks, 2 x week, 35-minute session duration. Pool temperature 32.5 degrees centigrade. Pool length 25-metres. Each session consisted of mobility encouragement and supervision, and activities to stimulate the somato-sensory system utilising aquatic properties of buoyancy, turbulence, viscosity, warmth and hydrostatic pressure. Somato-sensory activities focused on stimulating touch and tactile exploration including objects of various shape, size, weight, contour, texture, elasticity, pliability, softness and hardness. Outcomes were measured by the Goal Attainment Scale (GAS) and included mobility distance, attendance, and timed tactile responsiveness to varying objects. Results: Mobility distance and attendance exceeded baseline expectations. Timed tactile responsiveness to varying objects also changed positively from baseline. Average scale scores were 1.00 with an overall GAS t-score of 63.69. Conclusions: Hydrotherapy can be a quantifiable physio-therapeutic option for persons with DSI. It provides a relatively safe environment for mobility and allows the somato-sensory system to be fully engaged - important for the DSI population. Implications: Hydrotherapy can be a measurable therapeutic option for a DSI person. Physiotherapists should consider hydrotherapy for DSI people. Hydrotherapy can offer unique physical properties for the DSI population not available on land.Keywords: chronic, disability, disease, rehabilitation
Procedia PDF Downloads 35514870 Evaluation of Cryoablation Procedures in Treatment of Atrial Fibrillation from 3 Years' Experiences in a Single Heart Center
Authors: J. Yan, B. Pieper, B. Bucsky, B. Nasseri, S. Klotz, H. H. Sievers, S. Mohamed
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Cryoablation is evermore applied for interventional treatment of paroxysmal (PAAF) or persistent atrial fibrillation (PEAF). In the cardiac surgery, this procedure is often combined with coronary arterial bypass graft (CABG) and valve operations. Three different methods are feasible in this sense in respect to practicing extents and mechanisms such as lone left atrial cryoablation, Cox-Maze IV and III in our heart center. 415 patients (68 ± 0.8ys, male 68.2%) with predisposed atrial fibrillation who initially required either coronary or valve operations were enrolled and divided into 3 matched groups according to deployed procedures: CryoLA-group (cryoablation of lone left atrium, n=94); Cox-Maze-IV-group (n=93) and Cox-Maze-III-group (n=8). All patients additionally received closure of the left atrial appendage (LAA) and regularly underwent three-year ambulant follow-up assessments (3, 6, 9, 12, 18, 24, 30 and 36 months). Burdens of atrial fibrillation were assessed directly by means of cardiac monitor (Reveal XT, Medtronic) or of 3-day Holter electrocardiogram. Herewith, attacks frequencies of AF and their circadian patterns were systemically analyzed. Furthermore, anticoagulants and regular rate-/rhythm-controlling medications were evaluated and listed in terms of anti-rate and anti-rhythm regimens. Concerning PAAF treatment, Cox Maze IV procedure provided therapeutically acceptable effect as lone left atrium (LA) cryoablation did (5.25 ± 5.25% vs. 10.39 ± 9.96% AF-burden, p > 0.05). Interestingly, Cox Maze III method presented a better short-term effect in the PEAF therapy in comparison to lone cryoablation of LA and Cox Maze IV (0.25 ± 0.23% vs. 15.31 ± 5.99% and 9.10 ± 3.73% AF-burden within the first year, p < 0.05). But this therapeutic advantage went lost during ongoing follow-ups (26.65 ± 24.50% vs. 8.33 ± 8.06% and 15.73 ± 5.88% in 3rd follow-up year). In this way, lone LA-cryoablation established its antiarrhythmic efficacy and 69.5% patients were released from the Vit-K-antagonists, while Cox Maze IV liberated 67.2% patients from continuous anticoagulant medication. The AF-recurrences mostly performed such attacks property as less than 60min duration for all 3 procedures (p > 0.05). In the sense of the circadian distribution of the recurrence attacks, weighted by ongoing follow-ups, lone LA cryoablation achieved and stabilized the antiarrhythmic effects over time, which was especially observed in the treatment of PEAF, while Cox Maze IV and III had their antiarrhythmic effects weakened progressively. This phenomenon was likewise evaluable in the therapy of circadian rhythm of reverting AF-attacks. Furthermore, the strategy of rate control was much more often applied to support and maintain therapeutic successes obtained than the one of rhythm control. Derived from experiences in our heart center, lone LA cryoablation presented equivalent effects in the treatment of AF in comparison to Cox Maze IV and III procedures. These therapeutic successes were especially investigable in the patients suffering from persistent AF (PEAF). Additional supportive strategies such as rate control regime should be initialized and implemented to improve the therapeutic effects of the cryoablations according to appropriate criteria.Keywords: AF-burden, atrial fibrillation, cardiac monitor, COX MAZE, cryoablation, Holter, LAA
Procedia PDF Downloads 20414869 Immunoliposomes Conjugated with CD133 Antibody for Targeting Melanoma Cancer Stem Cells
Authors: Chuan Yin
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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.Keywords: cancer stem cells, melanoma, immunoliposomes, CD133
Procedia PDF Downloads 38214868 Stability and Sensitivity Analysis of Cholera Model with Treatment Class
Authors: Yunusa Aliyu Hadejia
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Cholera is a gastrointestinal disease caused by a bacterium called Vibrio Cholerae which spread as a result of eating food or drinking water contaminated with feaces from an infected person. In this work we proposed and analyzed the impact of isolating infected people and give them therapeutic treatment, the specific objectives of the research was to formulate a mathematical model of cholera transmission incorporating treatment class, to make analysis on stability of equilibrium points of the model, positivity and boundedness was shown to ensure that the model has a biological meaning, the basic reproduction number was derived by next generation matrix approach. The result of stability analysis show that the Disease free equilibrium was both locally and globally asymptotically stable when R_0< 1 while endemic equilibrium has locally asymptotically stable when R_0> 1. Sensitivity analysis was perform to determine the contribution of each parameter to the basic reproduction number. Numerical simulation was carried out to show the impact of the model parameters using MAT Lab Software.Keywords: mathematical model, treatment, stability, sensitivity
Procedia PDF Downloads 9914867 The Limits of the Effectiveness of Digital Advertising: Demonstration by the Economic Approach of Measuring Advertising Effectiveness
Authors: Barkaoui Asma
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In our article, we use the economic approach of measuring advertising effectiveness to show the margin of advertising spread gained through digital communication. For economists, profit maximization depends on determining the optimal advertising budget. For this, they use the theories of the marginalist current to determine when the maximum level of benefits is reached. Using the economic approach we show the significant return on investment for advertisers. We then discuss the risks of perception of advertising pressure by consumers.Keywords: digital advertising, economic approach, effectiveness, pressure
Procedia PDF Downloads 30414866 Tensile strength and Elastic Modulus of Nanocomposites Based on Polypropylene/Linear Low Density Polyethylene/Titanium Dioxide Nanoparticles
Authors: Faramarz Ashenai Ghasemi, Ismail Ghasemi, Sajad Daneshpayeh
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In this study, tensile strength and elastic modulus of nanocomposites based on polypropylene/ linear low density polyethylene/ nano titanium dioxide (PP/LLDPE/TiO2) were studied. The samples were produced using a co-rotating twin screw extruder including 0, 2, 4 Wt .% of nano particles, and 20, 40, 60 Wt.% of LLDPE. The styrene-ethylene-butylene-styrene (SEBS) was used as comptabiliser. Tensile strength and elastic modulus were evaluated. The results showed that modulus was increased by 7% with addition of nano particles in comparison to PP/LLDPE. In addition, tensile strength was decreased.Keywords: PP/LLDPE/TiO2, nanocomposites, elastic modulus, tensile strength
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