Search results for: therapeutic drug monitoring

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Mamoon Masud, Suleman Mazhar

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Indus river basin’s irrigation system in Pakistan is extremely complex, spanning over 50,000 km. Maintenance and monitoring of this demands enormous resources. This paper describes the development of a streamlined and low-cost autonomous underwater vehicle (AUV) for the monitoring of irrigation canals including water quality monitoring and water theft detection. The vehicle is a hovering-type AUV, designed mainly for monitoring irrigation canals, with fully documented design and open source code. It has a length of 17 inches, and a radius of 3.5 inches with a depth rating of 5m. Multiple sensors are present onboard the AUV for monitoring water quality parameters including pH, turbidity, total dissolved solids (TDS) and dissolved oxygen. A 9-DOF Inertial Measurement Unit (IMU), GY-85, is used, which incorporates an Accelerometer (ADXL345), a Gyroscope (ITG-3200) and a Magnetometer (HMC5883L). The readings from these sensors are fused together using directional cosine matrix (DCM) algorithm, providing the AUV with the heading angle, while a pressure sensor gives the depth of the AUV. 2 sonar-based range sensors are used for obstacle detection, enabling the vehicle to align itself with the irrigation canals edges. 4 thrusters control the vehicle’s surge, heading and heave, providing 3 DOF. The thrusters are controlled using a proportional-integral-derivative (PID) feedback control system, with heading angle and depth being the controller’s input and the thruster motor speed as the output. A flow sensor has been incorporated to monitor canal water level to detect water-theft event in the irrigation system. In addition to water theft detection, the vehicle also provides information on water quality, providing us with the ability to identify the source(s) of water contamination. Detection of such events can provide useful policy inputs for improving irrigation efficiency and reducing water contamination. The AUV being low cost, small sized and suitable for autonomous maneuvering, water level and quality monitoring in the irrigation canals, can be used for irrigation network monitoring at a large scale.

Keywords: the autonomous underwater vehicle, irrigation canal monitoring, water quality monitoring, underwater line tracking

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

Procedia PDF Downloads 218

Authors: D. Velayadum, P. Sthandiwe , N. Maharaj, T. Munien, S. Ndamase, G. Zulu, S. Xulu, F. Oosthuizen

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Introduction and aims of the study: It is the responsibility of the pharmacist to manage drug-related problems in order to ensure the greatest benefit to the patient. In order to prevent drug-related morbidity, pharmacists should be aware of medicines that may contribute to certain drug-related problems due to their pharmacological action. In an attempt to assist healthcare practitioners to prevent drug-related morbidity (PDRM), indicators for prevention have been designed. There are currently no indicators available for primary health care in developing countries like South Africa, where the majority of the population access primary health care. There is, therefore, a need to develop such indicators, specifically with the aim of assisting healthcare practitioners in primary health care. Methods: A literature study was conducted to compile a comprehensive list of PDRM indicators as developed internationally using the search engines Google Scholar and PubMed. MESH term used to retrieve suitable articles was 'preventable drug-related morbidity indicators'. The comprehensive list of PDRM indicators obtained from the literature study was further evaluated for face validity. Face validity was done in duplicate by 2 sets of independent researchers to ensure 1) no duplication of indicators when compiling a single list, 2) inclusion of only medication available in primary healthcare, and 3) inclusion of medication currently available in South Africa. Results: The list of indicators, compiled from PDRM indicators in the USA, UK, Portugal, Australia, India, and Canada contained 324 PDRM. 184 of these indicators were found to be duplicates, and the duplications were omitted, leaving a final list of 140. The 140 PDRM indicators were evaluated for face-validity, and 97 were accepted as relevant to primary health care in South Africa. 43 indicators did not comply with the criteria and were omitted from the final list. Conclusion: This study is a first step in compiling a list of PDRM indicators for South Africa. It is important to take cognizance to the fact the health systems differ vastly internationally, and it is, therefore, important to develop country-specific indicators.

Keywords: drug-related morbidity, primary healthcare, South Africa, developing countries

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Authors: Jing Hu, Dong Yang

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With the increasingly difficult development and operating environment of exploration, there are many new challenges and difficulties in developing and exploiting oil and gas resources. These include the ability to dynamically monitor wells and provide data and assurance for the completion and production of high-cost and complex wells. A key technology in providing these assurances and maximizing oilfield profitability is real-time permanent reservoir monitoring. The emergence of optical fiber sensing systems has gradually begun to replace traditional electronic systems. Traditional temperature sensors can only achieve single-point temperature monitoring, but fiber optic sensing systems based on the Bragg grating principle have a high level of reliability, accuracy, stability, and resolution, enabling cost-effective monitoring, which can be done in real-time, anytime, and without well intervention. Continuous data acquisition is performed along the entire wellbore. The integrated package with the downhole pressure gauge, packer, and surface system can also realize real-time dynamic monitoring of the pressure in some sections of the downhole, avoiding oil well intervention and eliminating the production delay and operational risks of conventional surveys. Real-time information obtained through permanent optical fibers can also provide critical reservoir monitoring data for production and recovery optimization.

Keywords: PDHM, optical fiber, coiled tubing, photoelectric composite cable, digital-oilfield

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Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

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Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

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Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi

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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.

Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release

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Authors: Hyun-Woo Cho

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Earlier detection of incipient abnormal operations in terms of plant-wide process management is quite necessary in order to improve product quality and process safety. And generating warning signals or alarms for operating personnel plays an important role in process automation and intelligent plant health monitoring. Various methodologies have been developed and utilized in this area such as expert systems, mathematical model-based approaches, multivariate statistical approaches, and so on. This work presents a nonlinear empirical monitoring methodology based on the real-time analysis of massive process data. Unfortunately, the big data includes measurement noises and unwanted variations unrelated to true process behavior. Thus the elimination of such unnecessary patterns of the data is executed in data processing step to enhance detection speed and accuracy. The performance of the methodology was demonstrated using simulated process data. The case study showed that the detection speed and performance was improved significantly irrespective of the size and the location of abnormal events.

Keywords: detection, monitoring, process data, noise

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Authors: Rezvan Najafi, Korosh Heydari, Massoud Saidijam

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5-FU is a chemotherapeutic agent that has been used in colorectal cancer (CRC) treatment. However, it is usually associated with the acquired resistance, which decreases the therapeutic effects of 5-FU. miR-200c is involved in chemotherapeutic drug resistance, but its mechanism is not fully understood. In this study, the effect of inhibition of miR-200c in sensitivity of HCT-116 CRC cells to 5-FU was evaluated. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was evaluated using quantitative real- time PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were analyzed by western blotting. Annexin V and propidium iodide staining assay were applied for apoptosis detection. The caspase-3 activation was evaluated by an enzymatic assay. The results showed LNA-anti-miR-200c inhibited the expression of PTEN and E-cadherin protein, apoptosis and activation of caspase 3 compared with control cells. In conclusion, these results suggest that miR-200c as a prognostic marker can overcome to 5-FU chemoresistance in CRC.

Keywords: colorectal cancer, miR-200c, 5-FU resistance, E-cadherin, PTEN

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Firman Riyudha, Endrik Mifta Shaiful

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The spread of drug users is one kind of behavioral epidemiology that becomes a threat to every country in the world. This problem caused various crisis simultaneously, including financial or economic crisis, social, health, until human crisis. Most drug users are teenagers at school age. A new deterministic model would be constructed to determine the dynamics of the spread of drug users by considering level of education in a susceptible population. Based on the analytical model, two equilibria points were obtained; there were E₀ (zero user) and E₁ (endemic equilibrium). Existence of equilibrium and local stability of equilibria depended on the Basic Reproduction Ratio (R₀). This parameter was defined as the expected rate of secondary prevalence and primary prevalence in virgin population along spreading primary prevalence. The zero-victim equilibrium would be locally asymptotically stable if R₀ < 1 while if R₀ > 1 the endemic equilibrium would be locally asymptotically stable. The result showed that R₀ was proportional to the rate of interaction of each susceptible population based on educational level with the users' population. It is concluded that there was a need to be given a control in interaction, so that drug users population could be minimized. Numerical simulations were also provided to support analytical results.

Keywords: drugs users, level education, mathematical model, stability

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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Authors: Prakash Singh

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Many schools throughout the world are facing constant pressure to cope with the violence and drug abuse of learners who show little or no respect for acceptable and desirable social norms. These delinquent learners tend to harbour feelings of being beyond reproach because they strongly believe that it is well within their rights to engage in violent and destructive behaviour. Knives, guns, and other weapons appear to be more readily used by them on the school premises than before. It is known that learners smoke, drink alcohol, and use drugs during school hours, hence, their ability to concentrate, work, and learn, is affected. They become violent and display disruptive behaviour in their classrooms as well as on the school premises, and this atrocious behaviour makes it possible for drug dealers and gangsters to gain access onto the school premises. The primary purpose of this exploratory quantitative study was therefore to establish how tobephobia (TBP), caused by school violence and drug abuse, affects teaching and learning in schools. The findings of this study affirmed that poor discipline resulted in producing poor quality education. Most of the teachers in this study agreed that educating learners who consumed alcohol and other drugs on the school premises resulted in them suffering from TBP. These learners are frequently abusive and disrespectful, and resort to violence to seek attention. As a result, teachers feel extremely demotivated and suffer from high levels of anxiety and stress. The word TBP will surely be regarded as a blessing by many teachers throughout the world because finally, there is a word that will make people sit up and listen to their problems that cause real fear and anxiety in schools.

Keywords: aims and objectives of quality education, debilitating effects of tobephobia, fear of failure associated with education, learners' violent behaviour and drug abuse

Procedia PDF Downloads 275

Authors: Talita Veldsman, Elzette Fritz

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Many children attending special education present with sensory integration difficulties that hamper their learning and behaviour. These learners can benefit from therapeutic interventions as part of their classroom curriculum that can address sensory development and allow for holistic development to take place. A research study was conducted by utilizing socio-drama as a therapeutic intervention in the classroom in order to develop sensory integration skills. The use of socio-drama as therapeutic intervention proved to be a successful multi-disciplinary approach where education and psychology could build a bridge of growth and integration. The paper describes how socio-drama was used in the classroom and how these sessions were designed. The research followed a qualitative approach and involved six Afrikaans-speaking children attending special secondary school in the age group 12-14 years. Data collection included observations during the session, reflective art journals, semi-structured interviews with the teacher and informal interviews with the adolescents. The analysis found improved self-confidence, better social relationships, sensory awareness and self-regulation in the participants after a period of a year.

Keywords: education, sensory integration, sociodrama, classroom intervention, psychology

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Authors: Chandra Prayaga, Lakshmi Prayaga, Aaron Wade, Kyle Rank, Gopi Shankar Mallu, Sri Satya, Harsha Pola

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In today's tech-driven world, where connectivity shapes our daily lives, maintaining physical and emotional health is crucial. Athletic trainers play a vital role in optimizing athletes' performance and preventing injuries. However, a shortage of trainers impacts the quality of care. This study introduces a vision-based exercise monitoring system leveraging Google's MediaPipe library for precise tracking of bicep curl exercises and simultaneous posture monitoring. We propose a three-stage methodology: landmark detection, side detection, and angle computation. Our system calculates angles at the elbow, wrist, neck, and torso to assess exercise form. Experimental results demonstrate the system's effectiveness in distinguishing between good and partial repetitions and evaluating body posture during exercises, providing real-time feedback for precise fitness monitoring.

Keywords: physical health, athletic trainers, fitness monitoring, technology driven solutions, Google’s MediaPipe, landmark detection, angle computation, real-time feedback

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Authors: Maciej Zaręba, Sławomir Lasota

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Understanding the dependencies between the input signal, that controls the production system and signals, that capture its output, is of a great importance in intelligent systems. The method for identification of the relationship between signals in continuous monitoring of production systems is described in the paper. The method discovers the correlation between changes in the states derived from input signals and resulting changes in the states of output signals of the production system. The method is able to handle system inertia, which determines the time shift of the relationship between the input and output.

Keywords: manufacturing operation management, signal relationship, continuous monitoring, production systems

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Authors: Sunil Kamboj, Suman Bala, Vipin Saini

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Niosomes were formulated with an aim of enhancing the oral bioavailability of losartan potassium and formulated in different molar ratios of surfactant, cholesterol and dicetyl phosphate. The formulated niosomes were found in range of 54.98 µm to 107.85 µm in size. Formulations with 1:1 ratio of surfactant and cholesterol have shown maximum entrapment efficiencies. Niosomes with sorbitan monostearate showed maximum drug release and zero order release kinetics, at the end of 24 hours. The in vivo study has shown the significant enhancement in oral bioavailability of losartan potassium in rats, after a dose of 10 mg/kg. The average relative bioavailability in relation with pure drug solution was found 2.56, indicates more than two fold increase in oral bioavailability. A significant increment in MRT reflects the release retarding ability of the vesicles. In conclusion, niosomes could be a promising delivery of losartan potassium with improved oral bioavailability and prolonged release profiles.

Keywords: non-ionic surfactant vesicles, losartan potassium, oral bioavailability, controlled release

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Authors: Hatim Laalej, Salvador Sumohano-Verdeja, Thomas McLeay

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Monitoring of tool wear in milling operations is essential for achieving the desired dimensional accuracy and surface finish of a machined workpiece. Although there are numerous statistical models and artificial intelligence techniques available for monitoring the wear of cutting tools, these techniques cannot pin point which cutting edge of the tool, or which insert in the case of indexable tooling, is worn or broken. Currently, the task of monitoring the wear on the tool cutting edges is carried out by the operator who performs a manual inspection, causing undesirable stoppages of machine tools and consequently resulting in costs incurred from lost productivity. The present study is concerned with the development of a flute tracking system to segment signals related to each physical flute of a cutter with three flutes used in an end milling operation. The purpose of the system is to monitor the cutting condition for individual flutes separately in order to determine their progressive wear rates and to predict imminent tool failure. The results of this study clearly show that signals associated with each flute can be effectively segmented using the proposed flute tracking system. Furthermore, the results illustrate that by segmenting the sensor signal by flutes it is possible to investigate the wear in each physical cutting edge of the cutting tool. These findings are significant in that they facilitate the online condition monitoring of a cutting tool for each specific flute without the need for operators/engineers to perform manual inspections of the tool.

Keywords: machining, milling operation, tool condition monitoring, tool wear prediction

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

Abstract:

Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

Procedia PDF Downloads 137

Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh

Abstract:

The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.

Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers

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Authors: Amira Zrelli, Tahar Ezzedine

Abstract:

Routing protocol may enhance the lifetime of sensor network, it has a highly importance, especially in wireless sensor network (WSN). Therefore, routing protocol has a big effect in these networks, thus the choice of routing protocol must be studied before setting up our network. In this work, we implement the routing protocol collect tree protocol (CTP) which is one of the hierarchic protocols used in structural health monitoring (SHM). Therefore, to evaluate the performance of this protocol, we choice to work with Contiki system and Cooja simulator. By throughput and RSSI evaluation of each node, we will deduce about the utility of CTP in structural monitoring system.

Keywords: CTP, WSN, SHM, routing protocol

Procedia PDF Downloads 288

Authors: K. Bensafia, A. Mansour, G. Le Maillot, B. Clement, O. Reynet, P. Ariès, S. Haddab

Abstract:

This paper presents a system designed for wireless acquisition, the recording of electrocardiogram (ECG) signals and the monitoring of the heart’s health during surgery. This wireless recording system allows us to visualize and monitor the state of the heart’s health during a surgery, even if the patient is moved from the operating theater to post anesthesia care unit. The acquired signal is transmitted via a Bluetooth unit to a PC where the data are displayed, stored and processed. To test the reliability of our system, a comparison between ECG signals processed by a conventional ECG monitoring system (Datex-Ohmeda) and by our wireless system is made. The comparison is based on the shape of the ECG signal, the duration of the QRS complex, the P and T waves, as well as the position of the ST segments with respect to the isoelectric line. The proposed system is presented and discussed. The results have confirmed that the use of Bluetooth during surgery does not affect the devices used and vice versa. Pre- and post-processing steps are briefly discussed. Experimental results are also provided.

Keywords: electrocardiography, monitoring, surgery, wireless system

Procedia PDF Downloads 363

Authors: J. M. de Luis Ruiz, P. M. Sierra García, R. P. García, R. P. Álvarez, F. P. García, E. C. López

Abstract:

Given the evolution of viaducts, structural health monitoring requires more complex techniques to define their state. two alternatives can be distinguished: experimental and operational modal analysis. Although accelerometers or Global Positioning System (GPS) have been applied for the monitoring of structures under exploitation, the dynamic monitoring during the stage of construction is not common. This research analyzes whether GPS data can be applied to certain dynamic geometric controls of evolving structures. The fundamentals of this work were applied to the New Bridge of Cádiz (Spain), a worldwide milestone in bridge building. GPS data were recorded with an interval of 1 second during the erection of segments and turned to the frequency domain with Fourier transform. The vibration period and amplitude were contrasted with those provided by the finite element model, with differences of less than 10%, which is admissible. This process provides a vibration record of the structure with GPS, avoiding specific equipment.

Keywords: Fourier transform, global position system, operational modal analysis, structural health monitoring

Procedia PDF Downloads 237

Authors: Semiu Bello

Abstract:

Since the discovery of HIV/AIDS in 1981, it has been a major global challenge and its ravaging consequences have had negative imprints on both the affected and infected people. The challenge of HIV/AIDS does not only affect the developing countries of the world, the developed nations have had their share of the experiences. The disease has, therefore, attracted the attentions of national governments and international donor agencies with huge financial investments toward the eradication of the virus and its global menace. Socially, however, people living with HIV/AIDS have had to battle with an array of social challenges in regards to the infection; the social stigmas, which seem to be more prevalent in underdeveloped and developing societies. The social stigmas with which people living with HIV/AIDS have suffered from include, but not limited, to social isolation, group avoidance, loss of jobs, public ridicule and non-appointment to official and government positions. Given this background, this study examines the roles of therapeutic communication otherwise called patient-provider communication within a clinical environment, focusing on Olabisi Onabanjo University Teaching Hospital (OOUTH) Sagamu, Nigeria as a case study. In other words, this study will investigate the level of interpersonal communication, interactions, and relationships that often take place between people living with HIV/AIDS and health care providers including doctors, nurses and social workers. This study will methodologically adopt the in-depth interview to interview six members of people living with HIV/AIDS at OOUTH. The dimensions of the data will determine the policy prescriptions of this study, which as envisage, may contribute to the improved use of therapeutic communication by health care providers and may thereof improve the psychology of people living with HIV/AIDS in the face of any social stigma.

Keywords: health care providers, people living with HIV/AIDS, social stigma, therapeutic communication

Procedia PDF Downloads 227

Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

Abstract:

The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

Procedia PDF Downloads 312

Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

Abstract:

Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

Procedia PDF Downloads 124

Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

Abstract:

Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

Procedia PDF Downloads 605

Authors: Hyun-Woo Cho

Abstract:

The monitoring of industrial production quality has to be implemented to alarm early warning for unusual operating conditions. Furthermore, identification of their assignable causes is necessary for a quality control purpose. For such tasks many multivariate statistical techniques have been applied and shown to be quite effective tools. This work presents a process data-based monitoring scheme for production processes. For more reliable results some additional steps of noise filtering and preprocessing are considered. It may lead to enhanced performance by eliminating unwanted variation of the data. The performance evaluation is executed using data sets from test processes. The proposed method is shown to provide reliable quality control results, and thus is more effective in quality monitoring in the example. For practical implementation of the method, an on-line data system must be available to gather historical and on-line data. Recently large amounts of data are collected on-line in most processes and implementation of the current scheme is feasible and does not give additional burdens to users.

Keywords: detection, filtering, monitoring, process data

Procedia PDF Downloads 551