Search results for: high dosage drugs

Authors: C. Malça, P. Gonçalves, N. Alves, A. Mateus

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Regardless of the manufacturing process used, subtractive or additive, material, purpose and application, produced components are conventionally solid mass with more or less complex shape depending on the production technology selected. Aspects such as reducing the weight of components, associated with the low volume of material required and the almost non-existent material waste, speed and flexibility of production and, primarily, a high mechanical strength combined with high structural performance, are competitive advantages in any industrial sector, from automotive, molds, aviation, aerospace, construction, pharmaceuticals, medicine and more recently in human tissue engineering. Such features, properties and functionalities are attained in metal components produced using the additive technique of Rapid Prototyping from metal powders commonly known as Selective Laser Melting (SLM), with optimized internal topologies and varying densities. In order to produce components with high strength and high structural and functional performance, regardless of the type of application, three different internal topologies were developed and analyzed using numerical computational tools. The developed topologies were numerically submitted to mechanical compression and four point bending testing. Finite Element Analysis results demonstrate how different internal topologies can contribute to improve mechanical properties, even with a high degree of porosity relatively to fully dense components. Results are very promising not only from the point of view of mechanical resistance, but especially through the achievement of considerable variation in density without loss of structural and functional high performance.

Keywords: additive manufacturing, internal topologies, porosity, rapid prototyping, selective laser melting

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Authors: Dib Imane, Chettah Wahid, Khedidja Abdelhamid

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The plain of Gadaïne - Ain Yaghout, located in the wilaya of Batna (Eastern Algeria), experiences intensive human activities, particularly in agricultural practices which are accompanied by an increasing use of chemical fertilizers and manure. These activities lead to a degradation of the quality of water resources. In order to protect the quality of groundwater in this plain and formulate effective strategies to mitigate or avoid any contamination of groundwater, a risk assessment using the European method known as “COSTE Action 620” was applied to the mio-. plio-quaternary aquifer of this plain. Risk assessment requires the identification of existing dangers and their potential impact on groundwater by using a system of evaluation and weighting. In addition, it also requires the integration of the hydrogeological factors that influence the movement of contaminants by means of the intrinsic vulnerability maps of groundwater, which were produced according to the modified DRASTIC method. The overall danger on the plain ranges from very low to high. Farms containing stables, houses detached from the public sewer system, and sometimes manure piles were assigned a weighting factor expressing the highest degree of harmfulness; this created a medium to high danger index. Large areas for agricultural practice and grazing are characterized, successively, by low to very low danger. Therefore, the risks present at the study site are classified according to a range from medium to very high-risk intensity. These classes successively represent 3%, 49%, and 0.2% of the surface of the plain. Cultivated land and farms present a high to very high level of risk successively. In addition, with the exception of the salt mine, which presents a very high level of risk, the gas stations and cemeteries, as well as the railway line, represent a high level of risk.

Keywords: semi-arid, quality of water resources, risk assessment, vulnerability, contaminants

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Authors: Pankaj Prashar, Bimlesh Kumar, Ankita Sood, Anamika Gautam

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Pharmacovigilance (PV) is a rapidly growing discipline in pharmaceutical industries as an integral part of clinical research and drug development over the past few decades. PV carries a breadth of scope from drug manufacturing to its regulation with safer utilization. The fundamental steps of PV not only includes data collection and verification, coding of drugs with adverse drug reactions, causality assessment and timely reporting to the authorities but also monitoring drug manufacturing, safety issues, product quality and conduction of due diligence. Standardization of adverse event information, collaboration of multiple departments in different companies, preparation of documents in accordance to both governmental as well as non-governmental organizations (FDA, EMA, GVP, ICH) are the advancements in discipline of PV. De-harmonization, lack of predictive drug safety models, improper funding by government, non-reporting, and non-acceptability of ADRs by developing countries and reports directly from patients to the monitoring centres respectively are the major road backs of PV. Mandatory pharmacovigilance reporting, frequent inspections, funding by government, educating and training medical students, pharmacists and nurses in this segment can bring about empowerment in PV. This area needs to be addressed with a sense of urgency for the safe utilization of pharmaceuticals.

Keywords: pharmacovigilance, regulatory, adverse event, drug safety

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Authors: Naima Bouslah, Leila Bounabi, Farid Ouazib, Nabila Haddadine

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Conventional release dosage forms are known to provide an immediate release of the drug. Controlling the rate of drug release from polymeric matrices is very important for a number of applications, particularly in the pharmaceutical area. Hydrogels are polymers in three-dimensional network arrangement, which can absorb and retain large amounts of water without dissolution. They have been frequently used to develop controlled released formulations for oral administration because they can extend the duration of drug release and thus reduce dose to be administrated improving patient compliance. Tramadol is an opioid pain medication used to treat moderate to moderately severe pain. When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour. In the present work, we synthesized pH-responsive hydrogels of (hydroxyl ethyl methacrylate-co-acrylic acid), (HEMA-AA) for control drug delivery of tramadol in the gastro-intestinal tractus. The hydrogels with different acrylic acid content, were synthesized by free radical polymerization and characterized by FTIR spectroscopy, X ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). FTIR spectroscopy has shown specific hydrogen bonding interactions between the carbonyl groups of the hydrogels and hydroxyl groups of tramadol. Both the XRD and DSC studies revealed that the introduction of tramadol in the hydrogel network induced the amorphization of the drug. The swelling behaviour, absorptive kinetics and the release kinetics of tramadol in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 7.4) were also investigated. The hydrogels exhibited pH-responsive behavior in the swelling study. The (HEMA-AA) hydrogel swelling was much higher in pH =7.4 medium. The tramadol release was significantly increased when pH of the medium was changed from simulated gastric fluid (pH 1.2) to simulated intestinal fluid (pH 7.4). Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated.

Keywords: biopolymres, drug delivery, hydrogels, tramadol

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Authors: Wang Zhaoming, Shao Shegang, Chen Xiaorong, Qi Yanan, Tian Lei, Wang Jian

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This study conducts a comparative analysis of the spectral curves of asphalt pavements at various aging stages to improve road information extraction from high-resolution remote sensing imagery. By examining the distinguishing capabilities and spectral characteristics, the research aims to establish a pavement information extraction methodology based on China's high-resolution satellite images. The process begins by analyzing the spectral features of asphalt pavements to construct a spectral assessment model suitable for evaluating pavement health. This model is then tested at a national highway traffic testing site in China, validating its effectiveness in distinguishing different pavement aging levels. The study's findings demonstrate that the proposed model can accurately assess road health, offering a valuable tool for road maintenance planning and infrastructure management.

Keywords: spectral analysis, asphalt pavement aging, high-resolution remote sensing, pavement health assessment

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Authors: Deokyeong Choe, Sung Hun Youn, Younggon Kim, Chul Soo Shin

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L-Cysteine is extensively used as a supplement of pharmaceuticals, cosmetics, food and feed additives. It has obtained industrially by hydrolysis of human hair and poultry feathers. However, there are some problems such as the restriction of using materials from animals and the intractable waste pollution. The enzymatic conversion has been regarded as an environmental-friendly method. Currently, the biggest bottle-neck of enzymatic conversion is the low yield of L-cysteine due to the low substrate solubility. In this study, the method of enhancing the solubility of the substrate D,L-2-amino-Δ2-thiazoline-4-carboxylicacid (ATC) was developed and the enzymatic reaction at high concentration levels was performed. A large amount of substrate in aqueous solutions was dissolved by pH control using salts. As the pH of the solution increased, the solubility of ATC increased. It was thought that a shift of ATC from acid form (-COOH) to dissociated carboxylic group (-COO-) would improve its hydrophilicity leading to solubility increase. The highest solubility of ATC was 610 mM at pH 10.5, whereas the maximum reaction rate was obtained at pH 8.3. As a result, a high L-cysteine yield of 250 mM was achieved at pH 9.1, which was obtained from a combination of optimum pH conditions for ATC solubility and enzymatic conversion. This yield corresponds to approximately 18 times of that in previous reports.

Keywords: D, L-2-amino-Δ2-thiazoline-4-carboxylicacid, enzymatic conversion, high-substrate solubilization, L-Cysteine

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Authors: Yuan Wan, Shumei Cui, Shaopeng Wu

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Toroidal windings were taken advantage of to reduce of axial length of the motor, so as to match the applications that have severe restrictions on the axial length. But slotting in the out edge of the stator will decrease the heat-dissipation capacity of the water cooling of the housing. Besides, the windings in the outer slots will increase the copper loss, which will further increase the difficult for heat dissipation of the motor. At present, carbon-fiber composite retaining sleeve are increasingly used to be mounted over the magnets to ensure the rotor strength at high speeds. Due to the poor thermal conductivity of carbon-fiber sleeve, the cooling of the rotor becomes very difficult, which may result in the irreversible demagnetization of magnets for the excessively high temperature. So it is necessary to analyze the temperature rise of such motor. This paper builds a computational fluid dynamic (CFD) model of a toroidal-winding high-speed permanent magnet synchronous motor (PMSM) with water cooling of housing and forced air cooling of rotor. Thermal analysis was carried out based on the model and the factors that affects the temperature rise were investigated. Then thermal optimization for the prototype was achieved. Finally, a small-size prototype was manufactured and the thermal analysis results were verified.

Keywords: thermal analysis, temperature rise, toroidal windings, high-speed PMSM, CFD

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Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Mina Gholampour, Majid Saffarinia, Tayebeh Mohtashami, Amin Asadi Hieh

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The study aimed to assess the impact of positive psychology education on the social well-being of high school girls experiencing premenstrual syndrome (PMS). The statistical population comprised high school girls with PMS, with 30 randomly selected participants divided into two groups: 15 in the experimental group and 15 in the control group. The research employed a pre-test and post-test design using a standard questionnaire to evaluate premenstrual syndrome symptoms over a 7-day period before menstruation to a maximum of 2 days after menstruation, along with the Social Keys welfare questionnaire. During the study, the experimental group underwent an 8-session positive psychology group program. Data analysis was conducted using analysis of covariance. The results indicated a significant positive effect of positive psychology training on enhancing the social well-being of girls (p < 0.05). In conclusion, the findings suggest that positive psychology interventions can effectively increase social well-being among high school girls experiencing premenstrual syndrome.

Keywords: positive psychology, premenstrual syndrome, social welfare, girls

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Authors: Anthony Chidi Ezika, Gbolahan Joseph Adekoya, Emmanuel Rotimi Sadiku, Yskandar Hamam, Suprakas Sinha Ray

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High-energy-density polymer/ceramic composites require a high breakdown strength and dielectric constant. Interface polarization and electric percolation are responsible for the high dielectric constant. In order to create composite dielectrics, high conductivity ceramic particles are combined with polymers to increase the dielectric constant. In this study, bonding and the non-uniform distribution of charges in the ceramic/ceramic interface zone are investigated using density functional theory (DFT) modeling. This non-uniform distribution of charges is intended to improve the ceramic/ceramic interface's dipole polarization (dielectric response). The interfacial chemical bond formation can also improve the structural stability of the hybrid filler and, consequently, of the composite films. To comprehend the electron-transfer process, the density of state and electron localization function of the PPy with hybrid fillers are also studied. The polymer nanocomposite is anticipated to provide a suitable dielectric response for energy storage applications.

Keywords: energy storage, V₂C/ ZnS hybrid, polypyrrole, MXene, nanocomposite, dielectric

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Authors: Mohammad Hamed Asosheh

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The development of nanobiomaterials has opened new avenues in the field of biomedical engineering, offering unparalleled possibilities for advanced therapeutic applications. This study explores the synthesis and characterization of a distinct class of nanobiomaterials designed to enhance drug delivery systems and support tissue engineering. By integrating biodegradable polymers with bioactive nanoparticles, we have engineered a multifunctional platform that ensures controlled drug release, targeted delivery, and improved biocompatibility. Our findings demonstrate that these nanobiomaterials not only exhibit excellent mechanical properties but also promote cell proliferation and differentiation, making them ideal candidates for regenerative medicine. Furthermore, in vitro and in vivo assessments reveal that the engineered materials significantly reduce cytotoxicity while enhancing the therapeutic efficacy of encapsulated drugs. This research presents a promising approach to addressing current challenges in drug delivery and tissue regeneration, with the potential to revolutionize the treatment of chronic diseases and injury repair. Future work will focus on optimizing the material composition for specific clinical applications and conducting large-scale studies to evaluate long-term safety and effectiveness.

Keywords: nanobiomaterials, drug delivery systems, therapeutic efficacy, bioactive nanoparticles

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Authors: Pattanapon Kayansamruaj, Ha Thanh Dong, Nopadon Pirarat, Channarong Rodkhum

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Streptococcus iniae (SI) is a devastating pathogenic bacteria causing heavy mortality in farmed fish. The application of commercialized bacterin vaccine has been reported failures as the outbreaks of the new serotype of SI were emerged in farms after vaccination and subsequently caused severe losses. In the present study, we attempted to develop effective DNA vaccines against SI infection using Nile tilapia (Oreochromis niloticus) as an animal model. Two monovalent DNA vaccines were constructed by the insertion of coding sequences of cell wall-associated virulence factors-encoding genes, comprised of eno (α-enolase) and mtsB (hydrophobic membrane protein), into cytomegalovirus expression vector (pCI-neo). In the animal trial, 30-g Nile tilapia were injected intramuscularly with 15 µg of each vaccine (mock vaccine group was injected by naked pCI-neo) and maintained for 35 days prior challenging with pathogenic SI at the dosage of 107 CFU/fish. At 13 days post-challenge, the relative percent survival of pEno, pMtsB and mock vaccine were 57%, 45% and 27%, respectively. The expression levels of immune responses-associated genes, namely, IL1β, TNF-α, TGF-β, COX2, IL-6, IL-12 and IL-13, were investigated from the spleen of experimental animal at 7 days post-vaccination (PV) and 7 days post-challenge (PC) using quantitative RT-PCR technique. Generally, at 7 days PV, the pEno vaccinated group exhibited highest level of up-regulation (1.7 to 2.9 folds) of every gene, but TGF-β, comparing to pMtsB and mock vaccine groups. However, at 7 days PC, pEno group showed significant up-regulation (1.4 to 8.5 folds) of immune-related genes as similar as mock vaccine group, while pMtsB group had lowest level of up-regulation (0.7 to 3.3 folds). Summarily, this study indicated that the pEno and pMtsB vaccines could elicit the immune responses of the fish and the magnitude of gene expression at 7 days PV was also consistent with the protection level conferred by the vaccine.

Keywords: gene expression, DNA vaccine, Nile tilapia, Streptococcus iniae

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Authors: Dongping Fang, Lian Duan, Xiaojing Yuan, Mike Xu, Allyn Klunder, Kevin Tan, Suiting Cao, Yeqing Ji

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Accurate prediction of a medical condition with straight clinical evidence is a long-sought topic in the medical management and health insurance field. Although great progress has been made with machine learning algorithms, the medical community is still, to a certain degree, suspicious about the model's accuracy and interpretability. This paper presents an innovative hierarchical attention deep learning model to achieve good prediction and clear interpretability that can be easily understood by medical professionals. This deep learning model uses a hierarchical attention structure that matches naturally with the medical history data structure and reflects the member’s encounter (date of service) sequence. The model attention structure consists of 3 levels: (1) attention on the medical code types (diagnosis codes, procedure codes, lab test results, and prescription drugs), (2) attention on the sequential medical encounters within a type, (3) attention on the medical codes within an encounter and type. This model is applied to predict the occurrence of stage 3 chronic kidney disease (CKD3), using three years’ medical history of Medicare Advantage (MA) members from a top health insurance company. The model takes members’ medical events, both claims and electronic medical record (EMR) data, as input, makes a prediction of CKD3 and calculates the contribution from individual events to the predicted outcome. The model outcome can be easily explained with the clinical evidence identified by the model algorithm. Here are examples: Member A had 36 medical encounters in the past three years: multiple office visits, lab tests and medications. The model predicts member A has a high risk of CKD3 with the following well-contributed clinical events - multiple high ‘Creatinine in Serum or Plasma’ tests and multiple low kidneys functioning ‘Glomerular filtration rate’ tests. Among the abnormal lab tests, more recent results contributed more to the prediction. The model also indicates regular office visits, no abnormal findings of medical examinations, and taking proper medications decreased the CKD3 risk. Member B had 104 medical encounters in the past 3 years and was predicted to have a low risk of CKD3, because the model didn’t identify diagnoses, procedures, or medications related to kidney disease, and many lab test results, including ‘Glomerular filtration rate’ were within the normal range. The model accurately predicts members A and B and provides interpretable clinical evidence that is validated by clinicians. Without extra effort, the interpretation is generated directly from the model and presented together with the occurrence date. Our model uses the medical data in its most raw format without any further data aggregation, transformation, or mapping. This greatly simplifies the data preparation process, mitigates the chance for error and eliminates post-modeling work needed for traditional model explanation. To our knowledge, this is the first paper on an interpretable deep-learning model using a 3-level attention structure, sourcing both EMR and claim data, including all 4 types of medical data, on the entire Medicare population of a big insurance company, and more importantly, directly generating model interpretation to support user decision. In the future, we plan to enrich the model input by adding patients’ demographics and information from free-texted physician notes.

Keywords: deep learning, interpretability, attention, big data, medical conditions

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Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

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Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.

Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract

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Authors: P. Murugesan, G. Venkateswaran, V. A. Shanmuga Selvan

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Water used for brewing tea plays a major role in the quality of tea. Water with higher hardness gives very dark coloured brew. This study was conducted to determine the effect of water hardness and free residual chlorine on the quality of black tea liquor. Theaflavin (TF) and Thearubigin (TR) levels are lower in comparison with the tea brewed in distilled water. At the same time, there is an increase in High Polymerized Substance (HPS) and Total Liquor Colour (TLC). While water with higher hardness has a negative impact on tea brew, water with high concentration of free residual chlorine did not affect the quality of tea brew.

Keywords: Theaflavin, Thearubigin, high polymerised substance, total liquor colour, hardness, residual chlorine

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Authors: Ezzati Givi M., Ezzatigivi N., Eimani H.

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Trigeminal Neuralgia (TN) consists of painful attacks often triggered with general activities, which cause impairment and disability. The first line of treatment consists of pharmacotherapy. However, the occurrence of many side-effects limits its application. Acute pain relief is crucial for titrating oral drugs and making time for neurosurgical intervention. This study aimed to examine the long-term anesthetic effect of QX-314 and capsaicin in trigeminal neuralgia using an animal model. TN was stimulated by surgical constriction of the infraorbital nerve in rats. After seven days, anesthesia infiltration was done, and the duration of mechanical allodynia was compared. Thirty-five male Wistar rats were randomly divided into seven groups as follows: control (normal saline); lidocaine (2%); QX314 (30 mM); lidocaine (2%)+QX314 (15 mM); lidocaine (2%)+QX314 (22 mM); lidocaine (2%)+QX314 (30 mM); and lidocaine (2%)+QX314 (30 mM) +capsaicin (1μg). QX314 in combination with lidocaine significantly increased the duration of anesthesia, which was dose-dependent. The combination of lidocaine+QX314+capsaicin could significantly increase the duration of anesthesia in trigeminal neuralgia. In the present study, we demonstrated that the combination of QX-314 with lidocaine and capsaicin produced a long-lasting, reversible local anesthesia and was superior to lidocaine alone in the fields of the duration of trigeminal neuropathic pain blockage.

Keywords: trigeminal neuralgia, capsaicin, lidocaine, long-lasting

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Authors: Penchuk A. Vovkanych

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The adaptive changes in the respiratory system provide the background for the increase of aerobic capacity and sport results on the middle and long distances runners. Effect of such adaptive changes in the sport orienteering remains poorly investigated. Therefore our study was undertaken to reveal the adaptive changes in the respiration indices of high skilled orienteer athletes.

Keywords: adaptation, external, functional state, respiration, running, sport orienteering

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Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Farhina Haque, Chanyeop Park

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The high efficiency, high field, and high power density provided by wide bandgap (WBG) semiconductors and advanced power electronic converter (PEC) topologies enabled the dynamic control of power in medium to high voltage systems. Although WBG semiconductors outperform the conventional Silicon based devices in terms of voltage rating, switching speed, and efficiency, the increased voltage handling properties, high dv/dt, and compact device packaging increase local electric fields, which are the main causes of partial discharge (PD) in the advanced medium and high voltage applications. PD, which occurs actively in voids, triple points, and airgaps, is an inevitable dielectric challenge that causes insulation and device aging. The aging process accelerates over time and eventually leads to the complete failure of the applications. Hence, it is critical to mitigating PD. Sharp edges, airgaps, triple points, and bubbles are common defects that exist in any medium to high voltage device. The defects are created during the manufacturing processes of the devices and are prone to high-electric-field-induced PD due to the low permittivity and low breakdown strength of the gaseous medium filling the defects. A contemporary approach of mitigating PD by neutralizing electric fields in high power density applications is introduced in this study. To neutralize the locally enhanced electric fields that occur around the triple points, airgaps, sharp edges, and bubbles, electrets are developed and incorporated into high voltage applications. Electrets are electric fields emitting dielectric materials that are embedded with electrical charges on the surface and in bulk. In this study, electrets are fabricated by electrically charging polyvinylidene difluoride (PVDF) films based on the widely used triode corona discharge method. To investigate the PD mitigation performance of the fabricated electret films, a series of PD experiments are conducted on both the charged and uncharged PVDF films under square voltage stimuli that represent PWM waveform. In addition to the use of single layer electrets, multiple layers of electrets are also experimented with to mitigate PD caused by higher system voltages. The electret-based approach shows great promise in mitigating PD by neutralizing the local electric field. The results of the PD measurements suggest that the development of an ultimate solution to the decades-long dielectric challenge would be possible with further developments in the fabrication process of electrets.

Keywords: electrets, high power density, partial discharge, triode corona discharge

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Authors: Joseph Carl Macalintal, Erlinda Armovit

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Magnesium sulfate has been a mainstay in the management of preeclampsia and is associated with a decreased incidence of morbidity and mortality. The syndrome has an unpredictable course, sometimes rapidly evolving to full-blown disease. In patients with deteriorating status, it is indicated to terminate the pregnancy via cesarean section. The anesthesiologists would prefer to have the procedure done under regional anesthesia; however, there may be cases when neuraxial anesthesia is contraindicated, or a general anesthesia would permit prompt delivery of the fetus. A patient with severe preeclampsia was given magnesium sulfate intrapartum, wherein a primary cesarean section was indicated for arrest in cervical dilatation, and was performed under general anesthesia. The patient developed acute respiratory failure and the causes of this occurrence were investigated in this report. It was later found out that neither the hypermagnesemia nor the muscle relaxant alone caused the patient’s condition but the interaction between the two. The patient was managed expectantly at the intensive care unit (ICU) and was eventually extubated during the 1st post-operative day. Knowledge of this drug interaction would allow obstetricians to advise their patients and their family about the possibility of prolonged intubation and ICU admission. This would also bring to the anesthesiologists’ attention the need to decrease the dose of muscle relaxant and to prepare drugs for immediate decurarisation.

Keywords: eclampsia, magnesium sulfate, preeclampsia, rocuronium bromide

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Authors: J. Punj, R. K. Pandey, V. Darlong, K. Thangavel

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Background: Dural puncture epidural (DPE) technique has been introduced recently for labour analgesia however, no study has compared ropivacaine and levobupivacaine for the same. Methods: The primary aim of the study was to compare time to onset of the Numerical Pain Rating Score (NPRS) ≤ 1 in labour analgesia with both drugs. After obtaining ethics and patient consent, ASA I and ASA II parturient with single foetus in vertex presentation and cervical dilatation <5.0 cm were included. DPE was performed with 16/ 26 G combined spinal epidural (CSE) technique, and parturients randomized into two groups. In Group R ( Ropivacaine) 20 ml 0.125% ropivacaine+ fentanyl 2µg/ml was injected to a maximum of 20 ml in 20 minutes and in Group L (Levobupivacaine), 20 ml 0.125% levobupivacaine + fentanyl 2µg/ml was injected. Outcomes were assessed at 0.5,2,4,6,8,10,12,14,16,18,20 and 30 minutes, then every 90 minutes until delivery. Appropriate statistical analysis was done, and p value of <0.05 was considered statistically significant. Results: The median time to onset of NPRS ≤1 in both groups was comparable (group R= 16 minutes vs group L= 18 minutes (p = 0.076). Volume of drug for NPR ≤1 in both groups was also comparable (Group R 15.95± 2.03 ml vs Group L 16.35 ± 1.34 ml (p=0.47). Conclusion: DPE with 16 G epidural needle and 26 gauge spinal needle with both 0.125% ropivacaine and 0.125% levobupivacaine results in similar efficacy of labour analgesia.

Keywords: dural puncture epidural, labour analgesia, obstetric analgesia, hypotension

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Authors: Raul G. Angeles

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The Philippine government instituted major reforms in its educational system. The Department of Education pushes the K to 12 program that makes kindergarten mandatory and adds two years of senior high school to the country's basic education. In essence, the students’ stay in basic education particularly those who are supposedly going to college is extended. The majority of the students expressed that they will be taking the Academic Track of the Senior High School curriculum specifically the Science, Technology, Engineering and Mathematics (STEM) and General Academic (GA) strands. Almost certainly, instruction should match the students' styles and thus through this descriptive study a city survey was conducted to explore the teaching strategies preferences of junior high school students and teachers who will be promoted to senior high school during the Academic Year 2016-2017. This study was conducted in selected public and private secondary schools in Metro Manila. Questionnaires were distributed to students and teachers; and series of follow-up interviews were also carried out to generate additional information. Preferences of students are centered on employing innovations such as technology, cooperative and problem-based learning. While the students will still be covered by basic education their interests in science are sparking to a point where the usual teaching styles may no longer work to them and for that cause, altering the teaching methods is recommended to create a teacher-student style matching. Other effective strategies must likewise be implemented.

Keywords: curriculum development, effective teaching strategies, problem-based learning, senior high school, science education, technology

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Authors: Lina Martinez, Juan David Rivera Acevedo, Isabella Franco

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The informal economy plays a significant role in the job market in Colombia. Cali, the third largest city in the country, is characterized by a high percentage of socially and economically vulnerable population groups who take part in the urban informal economy, with street vending as their primary source of income. This paper studies the socio-economic dimensions of street vendors in Cali. In particular, it examines why they are unable to capitalize on their comparatively high earnings and are not likely to escape poverty even though they usually profit from government welfare and tax evasion due to the non-regulated character of informality. The analysis of an observational study and two surveys with 637 and 300 participants show that street vending is a cash-based day-to-day activity. Since most of the street vendors do not have access to formal banking systems, they depend on payday loans with incomparably high interest rates which absorb a large share of their income and maintain a continuous indebtedness. This is one of the main reasons why they are unable to improve their living conditions. However, the daily cash flow masks the high opportunity cost of loans and long-term deficits.

Keywords: Colombia, informal economy, payday loans, street vendors

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Authors: Yufeng Li, Yinan Ma, Jing Wu, Chengnian Long

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Infrared object detection aims at separating small and dim target from clutter background and its capabilities extend beyond the limits of visible light, making it invaluable in a wide range of applications such as improving safety, security, efficiency, and functionality. However, existing methods are usually sensitive to the noise of the input infrared image, leading to a decrease in target detection accuracy and an increase in the false alarm rate in high-noise environments. To address this issue, an infrared small target detection algorithm called YOLO-IR is proposed in this paper to improve the robustness to high infrared noise. To address the problem that high noise significantly reduces the clarity and reliability of target features in infrared images, we design a soft-threshold coordinate attention mechanism to improve the model’s ability to extract target features and its robustness to noise. Since the noise may overwhelm the local details of the target, resulting in the loss of small target features during depth down-sampling, we propose a deep and shallow feature fusion neck to improve the detection accuracy. In addition, because the generalized Intersection over Union (IoU)-based loss functions may be sensitive to noise and lead to unstable training in high-noise environments, we introduce a Wasserstein-distance based loss function to improve the training of the model. The experimental results show that YOLO-IR achieves a 5.0% improvement in recall and a 6.6% improvement in F1-score over existing state-of-art model.

Keywords: infrared small target detection, high noise, robustness, soft-threshold coordinate attention, feature fusion

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Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki

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Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution

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Authors: Syed Adnan, Javed Iqbal

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In urban and rural areas groundwater is the most economic natural source of drinking. Groundwater resources of Pakistan are degraded due to high population growth and increased industrial development. A study was conducted in district Peshawar to assess groundwater vulnerable zones using GIS based DRASTIC model. Six input parameters (groundwater depth, groundwater recharge, aquifer material, soil type, slope and hydraulic conductivity) were used in the DRASTIC model to generate the groundwater vulnerable zones. Each parameter was divided into different ranges or media types and a subjective rating from 1-10 was assigned to each factor where 1 represented very low impact on pollution potential and 10 represented very high impact. Weight multiplier from 1-5 was used to balance and enhance the importance of each factor. The DRASTIC model scores obtained varied from 47 to 147. Using quantile classification scheme these values were reclassified into three zones i.e. low, moderate and high vulnerable zones. The areas of these zones were calculated. The final result indicated that about 400 km2, 506 km2, and 375 km2 were classified as low, moderate, and high vulnerable areas, respectively. It is recommended that the most vulnerable zones should be treated on first priority to facilitate the inhabitants for drinking purposes.

Keywords: DRASTIC model, groundwater vulnerability, GIS in groundwater, drinking sources

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Authors: Soner Guler, Eylem Guzel, Mustafa Gülen

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Recently, concrete-filled steel tube columns are highly popular in high-rise buildings. The main aim of this study is to evaluate the axial load capacities of circular high strength concrete-filled steel tube columns according to Eurocode 4 (EC4) and American Concrete Institute (ACI) design codes. The axial load capacities of fifteen concrete-filled steel tubes stub columns were compared with design codes EU4 and ACI. The results showed that the EC4 overestimate the axial load capacity for all the specimens.

Keywords: concrete-filled steel tube column, axial load capacity, Eurocode 4, ACI design codes

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Authors: Mayandi Ramanathan

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Gas turbine blades see the most aggressive thermal stress conditions within the engine, due to high Turbine Entry Temperatures in the range of 1500 to 1600°C. The blades rotate at very high rotation rates and remove a significant amount of thermal power from the gas stream. At high temperatures, the major component failure mechanism is a creep. During its service over time under high thermal loads, the blade will deform, lengthen and rupture. High strength and stiffness in the longitudinal direction up to elevated service temperatures are certainly the most needed properties of turbine blades and gas turbine components. The proposed advanced Ti alloy material needs a process that provides a strategic orientation of metallic ordering, uniformity in composition and high metallic strength. The chemical composition of the proposed Ti alloy material (25% Ta/(Al+Ta) ratio), unlike Ti-47Al-2Cr-2Nb, has less excess Al that could limit the service life of turbine blades. Properties and performance of Ti-47Al-2Cr-2Nb and Ti-6Al-4V materials will be compared with that of the proposed Ti alloy material to generalize the performance metrics of various gas turbine components. This paper will involve the summary of the effects of additive manufacturing and heat treatment process conditions on the changes in the phase composition, grain structure, lattice structure of the material, tensile strength, creep strain rate, thermal expansion coefficient and fracture toughness at different temperatures. Based on these results, additive manufacturing and heat treatment process conditions will be optimized to fabricate turbine blade with Ti-43Al matrix alloyed with an optimized amount of refractory Ta metal. Improvement in service temperature of the turbine blades and corrosion resistance dependence on the coercivity of the alloy material will be reported. A correlation of phase composition and creep strain rate will also be discussed.

Keywords: high temperature materials, aerospace, specific strength, creep strain, phase composition

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Authors: Piotr Fiszeder, Marcin Fałdziński, Peter Molnár

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The dynamic conditional correlation model of Engle (2002) is one of the most popular multivariate volatility models. However, this model is based solely on closing prices. It has been documented in the literature that the high and low price of the day can be used in an efficient volatility estimation. We, therefore, suggest a model which incorporates high and low prices into the dynamic conditional correlation framework. Empirical evaluation of this model is conducted on three datasets: currencies, stocks, and commodity exchange-traded funds. The utilisation of realized variances and covariances as proxies for true variances and covariances allows us to reach a strong conclusion that our model outperforms not only the standard dynamic conditional correlation model but also a competing range-based dynamic conditional correlation model.

Keywords: volatility, DCC model, high and low prices, range-based models, covariance forecasting

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Authors: Hadi Rouhi Belvirdi, Davoud Beheshtizadeh

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The increasing demand for sustainable construction materials has led to a growing interest in high-strength recycled concrete (HSRC). Utilizing recycled materials not only reduces waste but also minimizes the depletion of natural resources. This study explores the application of artificial intelligence (AI) techniques to model and predict the properties of HSRC. In the past two decades, the production levels in various industries and, consequently, the amount of waste have increased significantly. Continuing this trend will undoubtedly cause irreparable damage to the environment. For this reason, engineers have been constantly seeking practical solutions for recycling industrial waste in recent years. This research utilized the results of the compressive strength of 90-day high-strength recycled concrete. The method for creating recycled concrete involved replacing sand with crushed glass and using glass powder instead of cement. Subsequently, a feedforward artificial neural network was employed to model the compressive strength results for 90 days. The regression and error values obtained indicate that this network is suitable for modeling the compressive strength data.

Keywords: high-strength recycled concrete, feedforward artificial neural network, regression, construction materials

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