Search results for: drug therapy problem

Authors: Mohammad Mehdi Mazarei, Ali Asghar Behroozpoor

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In this paper, we define an optimization problem corresponding to smooth and nonsmooth functions which its optimal solution is the first derivative of these functions in a domain. For this purpose, a linear programming problem corresponding to optimization problem is obtained. The optimal solution of this linear programming problem is the approximate generalized first derivative. In fact, we approximate generalized first derivative of nonsmooth functions as tailor series. We show the efficiency of our approach by some smooth and nonsmooth functions in some examples.

Keywords: general derivative, linear programming, optimization problem, smooth and nonsmooth functions

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Authors: H. Mousavi, M. Sharifi, H. Pourvaziri

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Redundancy Allocation Problem (RAP) is a well-known mathematical problem for modeling series-parallel systems. It is a combinatorial optimization problem which focuses on determining an optimal assignment of components in a system design. In this paper, to be more practical, we have considered the problem of redundancy allocation of series system with interval valued reliability of components. Therefore, during the search process, the reliabilities of the components are considered as a stochastic variable with a lower and upper bounds. In order to optimize the problem, we proposed a simulated annealing based on cloud theory (CBSAA). Also, the Monte Carlo simulation (MCS) is embedded to the CBSAA to handle the random variable components’ reliability. This novel approach has been investigated by numerical examples and the experimental results have shown that the CBSAA combining MCS is an efficient tool to solve the RAP of systems with interval-valued component reliabilities.

Keywords: redundancy allocation problem, simulated annealing, cloud theory, monte carlo simulation

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Authors: Sunidhi Sood, Drashti Narendrakumar Shah, Aakarsh Sharma, Nirali Harsh Panchal, Maria Karizhenskaia

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Cancer is a global health concern, causing a significant number of deaths, with chemotherapy being a standard treatment method. However, chemotherapy often induces side effects that profoundly impact the physical and emotional well-being of patients, lowering their overall quality of life (QoL). This research aims to investigate the potential of music and art therapy as holistic adjunctive therapy for cancer patients undergoing chemotherapy, offering non-pharmacological support. This is achieved through a comprehensive review of existing literature with a focus on the following themes, including stress and anxiety alleviation, emotional expression and coping skill development, transformative changes, and pain management with mood upliftment. A systematic search was conducted using Medline, Google Scholar, and St. Lawrence College Library, considering original, peer-reviewed research papers published from 2014 to 2023. The review solely incorporated studies focusing on the impact of music and art therapy on the health and overall well-being of cancer patients undergoing chemotherapy in North America. The findings from 16 studies involving pediatric oncology patients, females affected by breast cancer, and general oncology patients show that music and art therapies significantly reduce anxiety (standardized mean difference: -1.10) and improve perceived stress (median change: -4.0) and overall quality of life in cancer patients undergoing chemotherapy. Furthermore, music therapy has demonstrated the potential to decrease anxiety, depression, and pain during infusion treatments (average changes in resilience scale: 3.4 and 4.83 for instrumental and vocal music therapy, respectively). This data calls for consideration of the integration of music and art therapy into supportive care programs for cancer patients undergoing chemotherapy. Moreover, it provides guidance to healthcare professionals and policymakers, facilitating the development of patient-centered strategies for cancer care in Canada. Further research is needed in collaboration with qualified therapists to examine its applicability and explore and evaluate patients' perceptions and expectations in order to optimize the therapeutic benefits and overall patient experience. In conclusion, integrating music and art therapy in cancer care promises to substantially enhance the well-being and psychosocial state of patients undergoing chemotherapy. However, due to the small population size considered in existing studies, further research is needed to bridge the knowledge gap and ensure a comprehensive, patient-centered approach, ultimately enhancing the quality of life (QoL) for individuals facing the challenges of cancer treatment.

Keywords: anxiety, cancer, chemotherapy, depression, music and art therapy, pain management, quality of life

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Nathalie Bolding, Marta Montero, Joaquim Cevallos, Juan F. Martin-Lazaro

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Background: Inhaled epoprostenol (iEPO) have been shown to improve PaO2:FiO2 (PF) in combination with bronchodilators (BD). However, there is not an available device to deliver these two therapies concomitantly. We describe a new method to provide this therapy successfully. Objective: To evaluate the response to continuous nebulization of iEPO and intermittent nebulization of Salbutamol/Ipratropium bromide in adults with severe respiratory failure through a double mesh nebulisation in tandem. Methods: This observational study included two mechanical ventilated adults under hourly ventilatory, gasometrical and clinical measurements during 48h. Both had severe respiratory failure treated with continuous iEPO (50 – 200 micrograms/h) and BD (Salbutamol 2.5 mg and Ipratropium bromide 500 mcg every 6 hours) through double mesh nebulisation (Aerogen solo®) placed in tandem in the dry side of the humidificator. The primary endpoints were the variables associated with a positive response to this tandem nebulised therapy (PaFiO2 index, ROX index). Secondary endpoints were laboratory (ABG) clinical and ventilatory variables. Statistical analysis (SPSS v29) included linear regression and ANOVA. Results: The patients included (n=2) survived, both extubated, one after ECMO therapy. Severe acute respiratory failure had a positive response rate to continuous iEPO and intermittent BD: PaFiO2 increased (7.40 to 30.91; P75: 27%) as well as ROX index (2.91 to 11.43; P75: 33%). There was a linear correlation of improvement between iEPO with PaFiO2 (ANOVA, r=0.393, p<0.002) and ROX (r=0.419, p<0.001). iEPO+BD therapy did not show any complications. Conclusion: Continuous and intermittent mesh tandem nebulisation can be effectively delivered with this method with a positive effect in ventilatory parameters without observed complications. Randomised studies will be able to provide reassurance in this new therapy.

Keywords: tandem, mesh, nebulisers, pulmonary, vasoldilators, bronchodilators, respiratory, failure

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Authors: Atiqah Binti Ab Aziz

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Background: It has been estimated that about 250 million people all over the world suffer from osteoarthritis (OA). Thus, OA is a major health problem in urgent need of better treatment. Problem statement: Current therapies for OA can temporarily relieve clinical symptoms and for pain management, rather than preventing or curing OA. Total knee replacement performed at the end stage of the disease is considered the only cure available. Objectives: This article aimed to explore the potential of treating osteoarthritis via the CRISPR Cas system. Methods: Articles that relate to the application of the CRISPR Cas system in osteoarthritis were extracted, categorized, and reviewed through the PRISMA method using PubMed, an engine published from November 2016 to November 2021. Results: There were 30 articles screened. Articles that fall under the categories of non-English articles, full articles that were not available, articles that were not an original articles were excluded. Ultimately, 13 articles were reviewed. Discussion: This review provides an information on the introduction of CRISPR and discussed on their mechanism of actions in extracted studies for OA treatment. Conclusions: It can be seen that not many medical research utilize the CRISPR Cas system as part of the method in the treatment of OA. Hence exploring the extent of the usage of the CRISPR Cas system in OA treatment is important to determine the research gap and point out at which of the research is needed further investigation to avoid redundancy of existing research and ensure the novelty of the research.

Keywords: osteoarthritis, treatment, CRISPR, review, therapy

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Authors: Ambika Selvaraj

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Magnetic iron oxide nanoparticles (IO) of < 20nm (superparamagnetic) become promising tool in cancer therapy, and integrated nanodevices for cancer detection and screening. The obstacles include particle heterogeneity and cost. It can be overcome by developing monodispersed nanoparticles in economical approach. We have successfully synthesized < 7 nm IO by low temperature controlled technique, in which Fe0 is sandwiched between stabilizer and Fe2+. Size analysis showed the excellent size control from 31 nm at 33°C to 6.8 nm at 10°C. Resultant monodispersed IO were found to be stable for > 50 reuses, proved its applicability in biomedical applications.

Keywords: low temperature synthesis, hybrid iron nanoparticles, cancer therapy, biomedical applications

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Authors: Yasin I. Tayem, Jamil Ahmed, Mahmood Bahzad, Abdullah Alnama, Fahad Al Asfoor, Mahmood A. Jalil, Mohammed Radhi, Ahmed Alenezi, Khalid A. J. Al-Khaja

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Drug-drug interactions (DDIs) represent a significant cause of patient’s morbidity and mortality. The rate of DDIs is rapidly increasing worldwide with the increasing proportion of ageing population and frequent requirement of polypharmacy-prescription of multiple drugs to treat comorbidities. Prescribing physicians are responsible for checking their prescriptions for the presence and severity of DDIs. However, since a large number of new drugs are approved and marketed every year, new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely only upon their previous knowledge of medicine to avoid potential DDIs. The aim of this study was to explore the perceptions of physicians working at primary healthcare centers in Bahrain towards DDIs and how they manage them during their practice. Methodology: In this cross-sectional study, physicians working at all governmental primary healthcare centers in Bahrain were invited to voluntarily, privately and anonymously respond to a self-administered questionnaire. The questionnaire aims to assess their self-reported knowledge of DDIs and how they check for them in their practice. The participants were requested to provide socio demographic data and information related to their attitudes towards DDIs including strategies they employ for detecting and managing them, and their awareness of drugs which commonly cause DDIs. At the end of the questionnaire, an open-ended item was added to allow participants to further add any comment. Findings and Conclusions: The study is going on currently, and the results and conclusions will be presented at the conference.

Keywords: awareness, drug interactions, health centres, physicians

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Authors: M. Helen

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Chemical graph serves as a convenient model for any real or abstract chemical system. Dendrimers are novel three dimensional hyper branched globular nanopolymeric architectures. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Dendrimers like poly L lysine (PLL), poly-propylene imine (PPI) and poly-amidoamine (PAMAM), etc., are used as gene carrier in drug delivery system because of their chemical characteristics. These characteristics of chemical compounds are analysed using topological indices (invariants under graph isomorphism) such as Wiener index, Zagreb index, etc., Prof. V. R. Kulli motivated by the application of Zagreb indices in finding the total π energy and derived Gourava indices which is an improved version over Zagreb indices. In this paper, we study the structure of PLL-Dendrimer that has the following applications: reduction in toxicity, colon delivery, and topical delivery. Also, we determine first and second Gourava indices, first and second hyper Gourava indices, product and sum connectivity Gourava indices for PLL-Dendrimer. Gourava Indices have found applications in Quantitative Structure-Property Relationship (QSPR)/ Quantitative Structure-Activity Relationship (QSAR) studies.

Keywords: connectivity Gourava indices, dendrimer, Gourava indices, hyper GouravaG indices

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Authors: Jessica Gladden

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Yoga has been accepted in the majority of communities in the United States as a method of assisting individuals with improving their physical health. Both community yoga classes and yoga-based therapy have been shown to be highly useful for individual’s mental health. Yoga-based therapy has been supported by research to be an evidence-based practice for individuals experiencing anxiety, depression, and disordered eating and for those experiencing post traumatic stress disorder in the wake of trauma. Many individuals who have experienced trauma, as well as other mental health diagnoses, are either very disconnected from their physical bodies or feel unsafe in their bodies. Yoga can be a method of creating safety and control in the body. This is recommended by some of the leading researchers in trauma therapy as a beginning step towards finding safety in the body in order to begin to work on the additional mental health challenges before addressing other long-term challenges. Unfortunately, yoga for physical and mental health is underutilized in black and brown communities despite the research regarding the benefits. Very few studies have examined the barriers to access to yoga for black, brown, and indigenous individuals. This study interviewed 15 yoga practitioners who identified as black or brown and explored the barriers they see in their communities related to accessing yoga and yoga-based services. Several of the themes reported include not feeling welcome, cost of services, time, and cultural/ religious components. Methods for reducing barriers will also be discussed.

Keywords: yoga, sport, barrier, black

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Authors: H.Karnezi, K. Tierney

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Childhood fears that persist over time and interfere with the children’s normal functioning may have detrimental effects on their social and emotional development. Cognitive behavior therapy is considered highly effective in treating fears and anxieties. However, given that many childhood fears are based on fantasy, the applicability of CBT may be hindered by cognitive immaturity. Furthermore, a lack of motivation to engage in therapy is another commonly encountered obstacle. The purpose of this study was to introduce and evaluate a more developmentally appropriate intervention model, specifically designed to provide phobic children with the motivation to overcome their fears. To this end, principles and techniques from cognitive and behavior therapies are incorporated into the ‘Drama in Education’ model. The Cognitive Behaviour Drama (CBD) method involves using the phobic children’s creativity to involve them in the therapeutic process. The children are invited to engage in exciting fictional scenarios tailored around their strengths and special interests. Once their commitment to the drama is established, a problem that they will feel motivated to solve is introduced. To resolve it, the children will have to overcome a number of obstacles culminating in an in vivo confrontation with the fear stimulus. The study examined the application of the CBD model in three single cases. Results in all three cases shown complete elimination of all fear-related symptoms. Preliminary results justify further evaluation of the Cognitive Behaviour Drama model. It is time and cost-effective, ensuring the clients' immediate engagement in the therapeutic process.

Keywords: phobias, autism, intervention, drama

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Authors: Rajni Kant Panik

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The aim of the present study was to develop and evaluate mupirocin loaded nanoparticle incorporated into hydrogel as an infected wound healer. Incorporated Nanoparticle in hydrogel provides a barrier that effectively prevents the contamination of the wound and further progression of infection to deeper tissues. Hydrogel creates moist healing environment on wound space with good fluid absorbance. Nanoparticles were prepared by double emulsion solvent evaporation method using different ratios of PLGA polymer and the hydrogels was developed using sodium alginate and gelatin. Further prepared nanoparticles were then incorporated into the hydrogels. The formulations were characterized by FT-IR and DSC for drug and polymer compatibility and surface morphology was studied by TEM. Nanoparticle hydrogel were evaluated for their size, shape, encapsulation efficiency and for in vitro studies. The FT-IR and DSC confirmed the absence of any drug polymer interaction. The average size of Nanoparticle was found to be in range of 208.21-412.33 nm and shape was found to be spherical. The maximum encapsulation efficiency was found to be 69.03%. The in vitro release profile of Nanoparticle incorporated hydrogel formulation was found to give sustained release of drug. Antimicrobial activity testing confirmed that encapsulated drug preserve its effectiveness. The stability study confirmed that the formulation prepared were stable. Present study complements our finding that mupirocin loaded Nanoparticle incorporated into hydrogel has the potential to be an effective and safe novel addition for the release of mupirocin in sustained manner, which may be a better option for the management of wound. These finding also supports the progression of antibiotic via hydrogel delivery system is a novel topical dosage form for the management of wound.

Keywords: hydrogel, nanoparticle, PLGA, wound healing

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Authors: N. F. Jamaluddin, N. A. H. Aizam

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This paper explains the educational timetabling problem, a type of scheduling problem that is considered as one of the most challenging problem in optimization and operational research. The university examination timetabling problem (UETP), which involves assigning a set number of exams into a set number of timeslots whilst fulfilling all required conditions, has been widely investigated. The limitation of available timeslots and resources with the increasing number of examinations are the main reasons in the difficulty of solving this problem. Dynamical change in the examination scheduling system adds up the complication particularly in coping up with the demand and new requirements by the communities. Our objective is to investigate these demands and requirements with subjects taken from Universiti Malaysia Terengganu (UMT), through questionnaires. Integer linear programming model which reflects the preferences obtained to produce an effective examination timetabling was formed.

Keywords: demands, educational timetabling, integer linear programming, scheduling, university examination timetabling problem (UETP)

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Authors: Uyanga Sukhbaatar, Ahmed Lbath, Mendamar Majig

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The Orienteering Problem is the most known example to start modeling tourist trip design problem. In order to meet tourist’s interest and constraint the OP is becoming more and more complicate to solve. The Multi Constraint Team Orienteering Problem with Time Windows is the last extension of the OP which differentiates from other extensions by including more extra associated constraints. The goal of the MCTOPTW is maximizing tourist’s satisfaction score in same time not to violate any of these constraints. This paper presents a genetic algorithmic approach to tackle the MCTOPTW. The benchmark data from literature is tested by our algorithm and the performance results are compared.

Keywords: multi constraint team orienteering problem with time windows, genetic algorithm, tour planning system

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Authors: Arpita Roy, Navneeta Bharadvaja

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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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Authors: Swapnila V. Vanshiv, Hemant P. Joshi, Atul B. Aware

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Current study illustrates the formulation of floating microspheres for purpose of gastroretention of Dipyridamole which shows pH dependent solubility, with the highest solubility in acidic pH. The formulation involved hollow microsphere preparation by using solvent evaporation technique. Concentrations of rate controlling polymer, hydrophilic polymer, internal phase ratio, stirring speed were optimized to get desired responses, namely release of Dipyridamole, buoyancy of microspheres, entrapment efficiency of microspheres. In the formulation, the floating microspheres were prepared by using ethyl cellulose as release retardant and HPMC as a low density hydrophilic swellable polymer. Formulated microspheres were evaluated for their physical properties such as particle size and surface morphology by optical microscopy and SEM. Entrapment efficiency, floating behavior and drug release study as well the formulation was evaluated for in vivo gastroretention in rabbits using gamma scintigraphy. Formulation showed 75% drug release up to 10 hr with entrapment efficiency of 91% and 88% buoyancy till 10 hr. Gamma scintigraphic studies revealed that the optimized system was retained in the gastric region (stomach) for a prolonged period i.e. more than 5 hr.

Keywords: Dipyridamole microspheres, gastroretention, HPMC, optimization method

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Manjusha R. Vagal, Shyam K. Shrivastava, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Reena Engineer, Amita Maheshwari, Atul Buduk

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Vaginal stenosis is a common side effect associated with pelvic radiotherapy in cervical cancer patients which contributes negatively to woman’s health and prevents adequate vaginal/cervical examination. Vaginal dilation with a dilator is routine practice and is internationally advocated as a prophylactic measure to preserve vaginal patency. This retrospective study was carried out with the aim to know the usefulness of vaginal dilation following pelvic radiation therapy in cervical cancer patients in India. Data from medical records of 183 cervical cancer patients, which met the study criteria, were collected related to the stage of the disease, treatment received, commencement period of dilation post radiation therapy, sexual status and side effects associated to dilation practice. Data related to vaginal dimensions as per the length of insertion of a small, medium and large dilator were collected on regular follow-ups until 36 months and/or more. Vaginal dimensions as measured with the length of medium dilator insertion were used for analysis of dilation therapy results using paired t-test. Patients who underwent vaginal dilation with dilator maintained vaginal patency, also the mean vaginal length significantly increased, from 8.02 cm ± 2.69 to 9.96 ± 2.89 cm with a p value <0.001. There was no significant difference found on vaginal patency with different intervals of initiation of dilation therapy. At the third year and more following dilation therapy, significant increase in vaginal length observed with a p value of 0.0001 in both sexually active and inactive patients. Compilation of vaginal dosage during brachytherapy was inadequate, and hence, the secondary objective of the study to determine the effect of radiotherapy on the outcome of rehabilitation intervention was not studied in detail. This retrospective study has found that dilation therapy with vaginal dilators post pelvic radiotherapy is effective in preventing vaginal stenosis and improving vaginal patency and cannot be substituted with vaginal intercourse. Sexual quality of life assessment in the Indian population needs much attention.

Keywords: dilator, sexually active, vaginal dilation, vaginal stenosis

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Authors: B. Özlük, A. Karaaslan

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This study has been conducted as a supplementary and relationship seeking study with the purpose of measuring the tendency and success of support among peers amid nursing students studying at university in solving interpersonal problems. The population of the study (N:279) is comprised of nursing students who are studying at one state and one private university in the province of Konya, while its sample is comprised of 231 nursing students who agreed to take part in the study voluntarily. As a result of this study, it has been determined that the peer support and interpersonal problem solving characteristics among students were at medium levels and that the interpersonal problem solving skills of students studying in the third year were higher than those of first and second year students. While the interpersonal problem solving characteristics of students who are aged 20 and over were found to be higher, no difference could be determined in terms of the interpersonal problem solving skills and tendencies among students, based on their gender and where they reside. A positive – to a medium degree – and significant relationship was determined between peer support and interpersonal problem solving skills, and it is possible to say that as peer support increases, so do the skills and tendencies to solve problems.

Keywords: nursing students, peer support, interpersonal problem, problem solving

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Elham Kazemi

Abstract:

Quadratic Assignment Problem (QAP) is one the combinatorial optimization problems about which research has been done in many companies for allocating some facilities to some locations. The issue of particular importance in this process is the costs of this allocation and the attempt in this problem is to minimize this group of costs. Since the QAP’s are from NP-hard problem, they cannot be solved by exact solution methods. Cuckoo Optimization Algorithm is a Meta-heuristicmethod which has higher capability to find the global optimal points. It is an algorithm which is basically raised to search a continuous space. The Quadratic Assignment Problem is the issue which can be solved in the discrete space, thus the standard arithmetic operators of Cuckoo Optimization Algorithm need to be redefined on the discrete space in order to apply the Cuckoo Optimization Algorithm on the discrete searching space. This paper represents the way of discretizing the Cuckoo optimization algorithm for solving the quadratic assignment problem.

Keywords: Quadratic Assignment Problem (QAP), Discrete Cuckoo Optimization Algorithm (DCOA), meta-heuristic algorithms, optimization algorithms

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Authors: Mir Mohammad Reza Hosseini

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In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

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Authors: Takahiro Hino, Michiharu Maeda

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Particle swarm optimization (PSO) is an optimization approach that achieves the social model of bird flocking and fish schooling. PSO works in continuous space and can solve continuous optimization problem with high quality. Set-based particle swarm optimization (SPSO) functions in discrete space by using a set. SPSO can solve combinatorial optimization problem with high quality and is successful to apply to the large-scale problem. In this paper, we present an algorithm of SPSO with status memory to decide the position based on the previous position for solving traveling salesman problem (TSP). In order to show the effectiveness of our approach. We examine SPSOSM for TSP compared to the existing algorithms.

Keywords: combinatorial optimization problems, particle swarm optimization, set-based particle swarm optimization, traveling salesman problem

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Authors: Lalitchandra J. Shah, Katarzyna Bialek, Melinda L. Clarke, Jessica L. Jansson

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Handwriting is essential to academic success; however, the current literature is limited in the identification of pre-handwriting skills. The purpose of this study was to identify the pre-handwriting skills, which occupational therapy practitioners deem important to handwriting success, as well as those which aid in intervention planning. The online survey instrument consisted of 33 questions that assessed various skills related to the development of handwriting, as well as captured demographic information. Both occupational therapists and occupational therapy assistants were included in the survey study. The survey found that the respondents were in agreement that purposeful scribbling, the ability of a child to copy (vertical/horizontal lines, circle, squares, and triangles), imitating an oblique cross, cognitive skills (attention, praxis, self-regulation, sequencing), grasp patterns, hand dominance, in hand manipulation skills (shift, translation, rotation), bilateral integration, stabilization of paper, crossing midline, and visual perception were important indicators of handwriting readiness. The results of the survey support existing research regarding the skills necessary for the successful development of handwriting in children.

Keywords: development, handwriting, occupational therapy, visual perceptual skills

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Authors: Emily Purdom, Rachel Robinson

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As the number of students worldwide requiring speech-language therapy, occupational therapy and mental health services during their school day increases, innovation is becoming progressively more important to meet the demand. Telepractice can be used to reach a greater number of students requiring specialized therapy while maintaining the highest quality of care. It can be provided in a way that is not only effective but ultimately more convenient for student, teacher and therapist without the added burden of travel. Teletherapy eradicates many hurdles to traditional on-site service delivery and helps to solve the pervasive shortage of certified professionals. Because location is no longer a barrier to specialized education plans for students with disabilities when teletherapy is conducted, there are many advantages that can be deployed. Increased frequency of engagement is possible along with students receiving specialized care from a clinician that may not be in their direct area. Educational teams, including parents, can work together more easily and engage in face-to-face, student-centered collaboration through videoconference. Practical strategies will be provided for connecting students with qualified therapists without the typical in-person dynamic. In most cases, better therapy outcomes are going to be achieved when treatment is most convenient for the student and educator. This workshop will promote discussion in the field of education to increase advocacy for remote service delivery. It will serve as a resource for those wanting to expand their knowledge of options for students with special needs afforded through innovation.

Keywords: education technology, innovation, student support services, telepractice

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Karen Hong

Abstract:

Smart tactile textiles are a series of textile-based products that incorporates smart embedded technology to be utilized as tactile therapeutic applications for 2 main groups of target users. The first group of users will be children with sensory processing disorder who are suffering from tactile sensory dysfunction. Children with tactile sensory issues may have difficulty tolerating the sensations generated from the touch of certain textures on the fabrics. A series of smart tactile textiles, collectively known as ‘Tactile Toys’ are developed as tactile therapy play objects, exposing children to different types of touch sensations within textiles, enabling them to enjoy tactile experiences together with interactive play which will help them to overcome fear of certain touch sensations. The second group of users will be the elderly or geriatric patients who are suffering from deteriorating sense of touch. One of the common consequences of aging is suffering from deteriorating sense of touch and a decline in motoric function. With the focus in stimulating the sense of touch for this particular group of end users, another series of smart tactile textiles, collectively known as ‘Tactile Aids’ are developed also as tactile therapy. This range of products can help to maintain touch sensitivity and at the same time allowing the elderly to enjoy interactive play to practice their hand-eye coordination and enhancing their motor skills. These smart tactile textile products are being designed and tested out by the end users and have proofed their efficacy as tactile therapy enabling the users to lead a better quality of life.

Keywords: smart textiles, embedded technology, tactile therapy, tactile aids, tactile toys

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Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

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Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

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Authors: Nyimas Annissa Mutiara Andini

Abstract:

There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

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