Search results for: oral hypoglycemic agent

Authors: Sanjal Gavande, Thomas Mazzuchi, Shahram Sarkani

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In a complex aerospace operational environment, identifying failures in a procedure involving multiple human-machine interactions are difficult. These failures could lead to accidents causing loss of hardware or human life. The likelihood of failure further increases if operational procedures are tested for a novel system with multiple human-machine interfaces and with no prior performance data. The existing approach in the literature of reviewing complex operational tasks in a flowchart or tabular form doesn’t provide any insight into potential system failures due to human decision-making ability. To address these challenges, this research explores an agent-based simulation approach for reliability assessment and fault detection in complex human-machine systems while utilizing a human decision-making model. The simulation will predict the emergent behavior of the system due to the interaction between humans and their decision-making capability with the varying states of the machine and vice-versa. Overall system reliability will be evaluated based on a defined set of success-criteria conditions and the number of recorded failures over an assigned limit of Monte Carlo runs. The study also aims at identifying high-likelihood failure locations for the system. The research concludes that system reliability and failures can be effectively calculated when individual human and machine agent states are clearly defined. This research is limited to the operations phase of a system lifecycle process in an aerospace environment only. Further exploration of the proposed agent-based and human decision-making model will be required to allow for a greater understanding of this topic for application outside of the operations domain.

Keywords: agent-based model, complex human-machine system, human decision-making model, system reliability assessment

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Authors: Xiao-Li Liu, Ling-Yun Zhao, Xing-Jie Liang, Hai-Ming Fan

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Owing to their unique properties, magnetic nanoparticles have been used as diagnostic and therapeutic agents for biomedical applications. Highly monodispersed magnetic nanoparticles with controlled particle size and surface coating have been successfully synthesized as a model system to investigate the effect of surface coating on the T2 relaxivity and specific absorption rate (SAR) under an alternating magnetic field, respectively. Amongst, by using mPEG-g-PEI to solubilize oleic-acid capped 6 nm magnetic nanoparticles, the T2 relaxivity could be significantly increased by up to 4-fold as compared to PEG coated nanoparticles. Moreover, it largely enhances the cell uptake with a T2 relaxivity of 92.6 mM-1s-1 for in vitro cell MRI. As for hyperthermia agent, SAR value increase with the decreased thickness of PEG surface coating. By elaborate optimization of surface coating and particle size, a significant increase of SAR (up to 74%) could be achieved with a minimal variation on the saturation magnetization (<5%). The 19 nm magnetic nanoparticles with 2000 Da PEG exhibited the highest SAR of 930 W•g-1 among the samples, which can be maintained in various simulated physiological conditions. This systematic work provides a general strategy for the optimization of surface coating of magnetic core for high performance MRI contrast agent and hyperthermia agent.

Keywords: magnetic nanoparticles, magnetic hyperthermia, magnetic resonance imaging, surface modification

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Authors: C. Akhras

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Change is the life blood of business. Dynamic factors inspire change yet may act as barriers, influencing the company’s position in the market and challenging its organizational mission and culture. Today, the business context has globalized with business enterprises in the North and South joint in mergers and the East forges a strategic alliance with the West. Moreover, given that very little remains stable in certain industries, national business goals in the millennial marketplaces might be rapid, accelerated, and differentiated growth while distinctive competitive advantage might mark new qualitative excellence in others. In a new age culture marked by change, organizations, leaders, and followers are impacted; indigenous business leaders seem to have a very important role to play in change management. This case study was carried out on 178 business employees employed in local industry to evaluate perceptions of indigenous business leadership, workplace assessment, and organizational change management in the Middle East and North Africa. Three research questions were posed: (1) In your work context, do you think business leaders are essentially changing agents? (2) In your work context, is workplace change more effective in business leaders perceived as a hierarchical change agent rather than those perceived as an empowering change agent? (3) In your work context, is workplace change more efficient in business leaders perceived as a hierarchical change agent rather than those perceived as an empowering change agent? The results of the study and its limitations imposed by time and space indicate that more comprehensive research is required in this area.

Keywords: catalyst, change management, business enterprise, workplace assessment

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Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

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Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

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Authors: Haozheng Luo, Ruiyang Qin

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People with visual impairments urgently need assistance, not only on the fundamental tasks such as guiding and retrieving objects but on the advanced like picturing the new environments. More than a guiding dog, they might want such devices that can provide linguistic interaction. Building on this idea, we aim to study the interaction between the robot agent and visually impaired people. In our research, we are going to develop a robot agent that will be able to analyze the test environment and answer the participants’ questions. We also will study the relevant issues regarding the interaction between human beings and the robot agents to figure out which and how the factors will affect the interaction.

Keywords: HRI, video question answering, visual question answering, natural language processing

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Authors: Maha Ali Al-Mohaya, Lubna Majed Al-Otaibi, Ebtissam Nassir Al-Bakr, Abdulrahman Al-Asmari

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Objectives: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods: Forty-two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results: The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P < 0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P > 0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion: It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. Further studies are required using a larger sample size to confirm this association and determine the prognostic values of these findings.

Keywords: oral lichen planus, cytokines, polymorphism, genetic

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Authors: Wanida Wonsawat

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Bioreduction of silver nanoparticles (AgNPs) from silver ions (Ag+) using water extract of Thai basil leaf was successfully carried out. The basil leaf extract provided a reducing agent and stabilizing agent for a synthesis of metal nanoparticles. Silver nanoparticles received from cut and uncut basil leaf was compared. The resulting silver nanoparticles are characterized by UV-Vis spectroscopy. The maximum intensities of silver nanoparticle from cut and uncut basil leaf were 410 and 420, respectively. The techniques involved are simple, eco-friendly and rapid.

Keywords: basil leaves, silver nanoparticles, green synthesis, plant extract

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Authors: Alex Contarino

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Professional sports leagues often have a “free agency” period, during which teams may sign players with expiring contracts.To promote parity, many leagues operate under a salary cap that limits the amount teams can spend on player’s salaries in a given year. Similarly, in fantasy sports leagues, salary cap drafts are a popular method for selecting players. In order to sign a free agent in either setting, teams must bid against one another to buy the player’s services while ensuring the sum of their player’s salaries is below the salary cap. This paper models the bidding process for a free agent as a constrained optimization problem that can be solved using linear programming. The objective is to determine the largest bid that a team should offer the player subject to the constraint that the value of signing the player must exceed the value of using the salary cap elsewhere. Iteratively solving this optimization problem for each available free agent provides teams with an effective framework for maximizing the talent on their rosters. The utility of this approach is demonstrated for team sport roster construction and fantasy sport drafts, using recent data sets from both settings.

Keywords: linear programming, optimization, roster management, salary cap

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

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Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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Authors: Mimoza Canga, Alketa Qafmolla, Vergjini Mulo, Irene Malagnino

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Aim: Assessment of oral health in young people aged 18-29 years after the Covid-19 pandemic in Albania. Materials and methods: The present study was conducted at the University of Medicine in Tirana, Albania, from March 2023 to September 2023. This is s cross-sectional study. In our research, 104 students participated, of which 64 were females (61.5%) and 40 were males (38.5%). In the present survey, the participants were divided into four age groups: 18-20, 21-23, 24-26, and 27-29 years old. Majority of the sample (69%) were 18-20 years. Participants were instructed to complete the questionnaire. The study had no dropouts. The current study was conducted in accordance to Helsinki declaration. Statistical analysis was performed using IBM SPSS Statistics Version 23.0, Microsoft Windows Linux, Chicago, IL, USA. Data were analyzed using analysis of variance (ANOVA). P ≤ 0.05 was considered statistically significant. Results: This study reported that 80 (76.9%) of the participants had passed Covid-19, while 24 (23.1%) of them had not passed Covid-19. Based on our data analysis, 70 (67.3%) of the participants had symptoms such as of fever 38°C- 40.5°C and headache. They stated that were treated with Azithromycin 500 mg tablets, Augmentin 625 mg tablets, Vitamin C 1000 mg, Magnesium, and Vitamin D. 40(38.4%) of the participants noticed hypersensitivity in gums (p = 0.004) and sensitive teeth (p = 0.001) after having passed Covid-19 compared to pre-pandemic. Nearly 40 (38.4%) of the participants who passed Covid-19 were treated with painful relievers for the gums and teeth, such as ibuprofen (Advil), used Sensodyne Toothpaste for sensitive teeth and Clove oil. Conclusion: Within the limitations of this study conducted in Albania, can concluded that Covid-19 has a direct impact on oral health.

Keywords: albania, Covid19, cross-sectional study, oral health

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Authors: Cliff Shunsheng Han

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Identifying the direct allergy cause that can be easily mitigated is the foundation to stop the allergy epidemic that has been started in the seventies. It has confirmed that the personal and social hygiene practices are associated with the allergy prevalence. But direct causes have been found, and proposed translational measures have not been effective. This study, assisted by a particular case of allergies, has seen the direct cause of allergies, developed a valid test resulted in lasting relief for allergies, and constructed theory describing general relationship between microbiota and host immune system. Saliva samples were collected from a subject for three years during which time the person experienced yearlong allergy, seasonal allergy, and remission of allergy symptoms. Bacterial DNA was extracted and 16S rRNA genes were profiled with Illumina sequencing technology. The analyzing results indicate that the possible direct cause of allergy is the lacking probiotic bacteria in the oral cavity, such as genera Streptococcus and Veilonella, that can produce metabolites to pacify immune system. Targeted promotion of those bacteria with a compound designed for them, has led to lasting remissions of allergic rhinitis. During the development of the translational measure, the subject's oral biofilm was completely destructed by a moderate fever due to an unrelated respiratory infection. The incident not only facilitated the development of the heat based microbiota reseeding procedure but also indicated a possible natural switch that subsequently increases the efficacy of the immune system previously restrained by metabolites from microbiota. These results lead to the proposal of a Theory of Negative Trigger (TNT) to describe the relationship between oral probiotics and immune system, in which probiotics are the negative trigger that will release the power of immune system when removed by fever or modern lifestyles. This study could open doors leading to further understanding of how the immune system functions under the influence of microbiota as well as validate simple traditional practices for healthy living.

Keywords: oral microbiome, allergy, immune system, infection

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Authors: Lyamine Guezouli, Kamel Barka, Zineb Seghir

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Wireless sensor and actor networks (WSANs) present a research challenge for different practice areas. Researchers are trying to optimize the use of such networks through their research work. This optimization is done on certain criteria, such as improving energy efficiency, exploiting node heterogeneity, self-adaptability and self-configuration. In this article, we present our proposal for BIFSA (Biologically-Inspired Framework for Wireless Sensor and Actor networks). Indeed, BIFSA is a middleware that addresses the key issues of wireless sensor and actor networks. BIFSA consists of two types of agents: sensor agents (SA) that operate at the sensor level to collect and transport data to actors and actor agents (AA) that operate at the actor level to transport data to base stations. Once the sensor agent arrives at the actor, it becomes an actor agent, which can exploit the resources of the actors and vice versa. BIFSA allows agents to evolve their genetic structures and adapt to the current network conditions. The simulation results show that BIFSA allows the agents to make better use of all the resources available in each type of node, which improves the performance of the network.

Keywords: wireless sensor and actor networks, self-management, genetic algorithm, agent.

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Authors: Sadaf Salek

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Introduction: Cats are susceptible to various health conditions, and one such ailment that can affect their oral health is epulis in their lips. Epulis refers to a benign tumor or growth that can develop in different areas of a cat's mouth, including the lips. While epulis is not life-threatening, it can still cause discomfort and affect a cat's overall quality of life. This essay aims to delve into the causes, symptoms, and treatment options for epulis in cat's lips, shedding light on this lesser-known oral condition. Causes: Epulis in a cat's lips can have several causes. Firstly, genetic predisposition plays a significant role, with certain breeds being more prone to developing these growths. Secondly, chronic irritation to the mouth, such as from dental diseases or foreign objects, can also contribute to the development of epulis. Lastly, hormonal imbalances, specifically an excess of estrogen, have been associated with the occurrence of these tumors in cats. Understanding these causes can help cat owners take preventive measures to reduce the risk of epulis in their feline companions. Symptoms: Identifying the symptoms of epulis in a cat's lips is vital for early intervention and effective treatment. The most common symptoms include swelling, redness, and the presence of a visible growth or lump on the lip. Cats with epulis may also exhibit drooling, difficulty eating, and a reluctance to groom themselves. Any change in eating habits or oral behavior should not be overlooked and prompt a visit to the veterinarian for a thorough examination. Treatment ptions: When it comes to treating epulis in a cat's lips, various options are available, depending on the size, location, and characteristics of the growth. The primary treatment involves surgical removal of the tumor. This procedure should be performed by a qualified veterinarian, ensuring complete excision of the mass while preserving as much healthy tissue as possible. In some cases, radiation therapy may be necessary, especially if the tumor is large or aggressive. Additionally, a veterinarian may recommend oral hygiene care and regular dental cleaning to prevent further growths and maintain the cat's oral health. Prevention and Care: Preventing epulis in a cat's lips is not always possible, especially if genetic factors are involved. However, certain preventive measures can minimize the risk of these growths. Maintaining good oral hygiene through regular brushing and the use of appropriate dental products can help prevent chronic irritation and dental diseases. Routine veterinary check-ups should also include thorough oral examinations to detect any abnormal growths or changes in the mouth at an early stage. Pet owners should be observant and seek veterinary care promptly for any signs of discomfort or changes in eating habits. Conclusion: Epulis in a cat's lips is a condition that requires attention and proper treatment. Understanding the causes, identifying symptoms, and exploring treatment options are of utmost importance to help improve a cat's oral health and overall well-being.

Keywords: fibroma, cat, lip, epulis

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Authors: Gajera Lalit, Shah Pranav, Shah Shailesh

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Venlafaxine hydrochloride has a short elimination half-life of 5 ± 2 hr, and absorption window in the upper part of gastrointestinal tract. The conventional tablets need to be administered two to three times a day and possess an oral bioavailability of 45%. The purpose of this study was to formulate gastroretentive effervescent floating tablets of Venlafaxine HCl. Different grades of HPMC namely K15M, K4M, K100M and E15LV were employed as swelling polymers whereas sodium bicarbonate was employed as gas generating agent. The direct compression method was employed for the formulation of tablets. The tablets were evaluated in terms of hardness, friability, weight variation, drug content, water uptake, in-vitro floating behavior and in-vitro drug release study. All the formulations exhibited very short floating lag time of < 1 min and total floating time of 12 hr. Formulation L3 containing 25 mg and 75 mg of HPMC E15 LV and HPMC K15M respectively exhibited complete drug release within 12 hrs.

Keywords: venlafaxine HCl, hydroxyl propyl methylcellulose, floating gastro retentive tablets, in-vitro drug release, non-fickian diffusion

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Authors: Ga-Young Lee, Hyun-Man Kim

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The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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Authors: Kimutai Joan Jepkorir, Moturi Wilkister Nyaora

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The practice of open defecation can be devastating for human health as well as the environment, and this practice persistence could be due to ingrained habits that individuals continue to engage in despite having a better alternative. Safe disposal of human excreta is essential for public health protection. This study sought to find if open defecation relates to fecal-oral infections in Burat and Ngaremara Wards in Isiolo County. This was achieved through conducting a cross-sectional study. Simple random sampling technique was used to select 385 households that were used in the study. Data collection was done by use of questionnaires and observation checklists. The result show that 66% of the respondents disposed-off fecal matter in a safe manner, whereas 34% disposed-off fecal matter in unsafe manner through open defecation. The prevalence proportions per 1000 of diarrhea and intestinal worms among children under-5 years of age were 142 and 21, respectively. The prevalence proportions per 1000 of diarrhea and typhoid among children over-5 years of age were 20 and 20, respectively.

Keywords: faecal-oral infections, open defecation, prevalence proportion, sanitation

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Authors: Ragy Raafat Gaber Attaalla

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PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

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Authors: Adam Beaunoyer, Cory Beaunoyer, Mohammed Elmorsy, Hanan Saleh

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This research aims to create a reinforcement learning agent capable of racing in challenging simulated environments with a low collision count. We present a reinforcement learning agent that can navigate challenging tracks using both a Deep Q-Network (DQN) and a Soft Actor-Critic (SAC) method. A challenging track includes curves, jumps, and varying road widths throughout. Using open-source code on Github, the environment used in this research is based on the 1995 racing game WipeOut. The proposed reinforcement learning agent can navigate challenging tracks rapidly while maintaining low racing completion time and collision count. The results show that the SAC model outperforms the DQN model by a large margin. We also propose an alternative multiple-car model that can navigate the track without colliding with other vehicles on the track. The SAC model is the basis for the multiple-car model, where it can complete the laps quicker than the single-car model but has a higher collision rate with the track wall.

Keywords: reinforcement learning, soft actor-critic, deep q-network, self-driving cars, artificial intelligence, gaming

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Authors: Yoshinori Matsuura, Saori Iwanaga

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The Great East Japan Earthquake occurred at 14:46 on Friday, March 11, 2011. It was the most powerful known earthquake to have hit Japan. The earthquake triggered extremely destructive tsunami waves of up to 40.5 meters in height. We focus on the ship’s evacuation from tsunami. Then we analyze about ships evacuation from tsunami using multi-agent simulation and we want to prepare for a coming earthquake. We developed a simulation model of ships that set sail from the port in order to evacuate from the tsunami considering the ship carrying dangerous goods.

Keywords: Ship’s evacuation, multi-agent simulation, tsunami

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Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

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Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

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Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Mhuji Kilonzo

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Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

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Authors: Albert Bou, Sebastian Dittert, Gianni de Fabritiis

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Advancing reinforcement learning (RL) requires tools that are flexible enough to easily prototype new methods while avoiding impractically slow experimental turnaround times. To match the first requirement, the most popular RL libraries advocate for highly modular agent composability, which facilitates experimentation and development. To solve challenging environments within reasonable time frames, scaling RL to large sampling and computing resources has proved a successful strategy. However, this capability has been so far difficult to combine with modularity. In this work, we explore design choices to allow agent composability both at a local and distributed level of execution. We propose a versatile approach that allows the definition of RL agents at different scales through independent, reusable components. We demonstrate experimentally that our design choices allow us to reproduce classical benchmarks, explore multiple distributed architectures, and solve novel and complex environments while giving full control to the user in the agent definition and training scheme definition. We believe this work can provide useful insights to the next generation of RL libraries.

Keywords: deep reinforcement learning, Python, PyTorch, distributed training, modularity, library

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Authors: Yasir Karabacak

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Objective: The aim of periodontal therapy is to control and eliminate inflammation in order halt disease progression. The initial periodontal therapy (IPT) including scaling and root planing (SRP) can control periodontal disease in most cases of periodontitis; also maintaining good oral hygiene by the patient is fundamental. The aim of this case report is to present IPT and to present 3-month follow-up results in a patient with periodontitis. Materials and Methods IPT of a 63-year-old non-smoker male with generalized periodontitis is presented. The patient had no history of systemic disease. The intraoral examination reveals marked gingival inflammation as well as plaque accumulation and significant calculus deposits. On radiographic examination, severe bone loss was evident. The patient was diagnosed with generalized advanced periodontitis. Initial periodontal therapy including oral hygiene instructions and quadrant-based SRP under local anesthesia was performed using hand and ultrasonic instruments. No antibiotics were prescribed. The patient was recalled 4 weeks after IPT. Results Favorable clinical improvement was obtained. Gingival inflammation was resolved significantly. A reduction of the mean probing depth from 2.4 mm at baseline to 1.9 mm was observed. The patient presented with a good standard of oral hygiene. The plaque scores decreased from 54.0% at baseline to 17.0%. In addition, the percentage of sites with bleeding on probing decreased from 80.0% at baseline to 44.0%. The patient was scheduled for maintenance therapy every three months. Conclusion: The level of oral hygiene has a great impact on periodontal treatment outcome and supports periodontal therapy properly.

Keywords: initial periodontal, therapy and follow-up in a periodontitis, patient, a case report

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Authors: Siti Navila

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Hedging as a kind of pragmatic competence is an essential part in achieving the goal in communication, especially in academic discourse where the process of sharing knowledge among academic community takes place. Academic discourse demands an appropriateness and modesty of an author or speaker in stating arguments, to name but few, by considering the politeness, being cautious and tentative, and differentiating personal opinions and facts in which these aspects can be achieved through hedging. This study was conducted to find the hedging devices used by students as well as to analyze how they use them in their oral presentation. Some oral presentations from English Department students of the State University of Jakarta on their Academic Presentation course final test were recorded and explored formally and functionally. It was found that the most frequent hedging devices used by students were shields from all hedging devices that students commonly used when they showed suggestion, stated claims, showed opinion to provide possible but still valid answer, and offered the appropriate solution. The researcher suggests that hedging can be familiarized in learning, since potential conflicts that is likely to occur while delivering ideas in academic contexts such as disagreement, criticism, and personal judgment can be reduced with the use of hedging. It will also benefit students in achieving the academic competence with an ability to demonstrate their ideas appropriately and more acceptable in academic discourse.

Keywords: academic discourse, hedging, hedging devices, lexical hedges, Meyer classification

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Authors: Shivayogi Charantimath

Abstract:

Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1^st and 2^nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1^st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1^st and 2^nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1^st week and 53.6% for 2^nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1^st week and 33.3% in 2^nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1^st week follow up and 0.000 for 2^nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

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Authors: L. K. Karimova, K. I. Shariukova, A. A. Kirpichnikova, E. A. Razuvalova

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This article deals with technology of virtual reconstruction of Kazan Imperial University of XIX - early XX centuries. The paper describes technologies of 3D-visualization of high-resolution models of objects of university space, creation of multi-agent system and connected with these objects organized database of historical sources, variants of use of technologies of immersion into the virtual environment.

Keywords: 3D-reconstruction, multi-agent system, database, university space, virtual reconstruction, virtual heritage

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Authors: Wafa Ghonaim

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Though quite fast on growth, Islamic financing at large, and its diverse instruments, is a controversial matter among scholars. This is evident from the ongoing debates on its Shariah compliance. Arguments, however, are inciting doubts and concerns among clients about its credibility, which is harming this lucrative sector. The work here investigates, particularly, some issues related to the Tawarruq instrument. The work examines the issues of linking Murabaha and Wakala contracts, the reselling of commodities to same traders, and the transfer of ownerships. The work affirms that a multi-agent smart electronic market design would facilitate Shariah compliance. The smart market exploits the rational decision-making capabilities of autonomous proxy agents that enable the clients, traders, brokers, and the bank buy and sell commodities, and manage transactions and cash flow. The smart electronic market design delivers desirable qualities that terminate the need for Wakala contracts and the reselling of commodities to the same traders. It also resolves the ownership transfer issues by allowing stakeholders to trade independently. The bank administers the smart electronic market and assures reliability of trades, transactions and cash flow. A multi-agent simulation is presented to validate the concept and processes. We anticipate that the multi-agent smart electronic market design would deliver Shariah compliance of personal financing to the aspiration of scholars, banks, traders and potential clients.

Keywords: Islamic finance, share'ah compliance, smart electronic markets design, multiagent systems

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Authors: Stefano A. Denes, Riccardo Tieghi, Giovanni Elia

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The buccal fat pad is a well-established tool in oral and maxillofacial surgery and its use has proved of value for the closure of oroantral communications. Oroantral communication may be a common complication after sequestrectomy in "Bisphosphonate-related osteonecrosis of the jaws". We report a clinical case of a 70-year-old female patient in bisphosphonate therapy presented with right maxillary sinusitis and oroantral communication after implants insertion. The buccal fat pad was used to close the defect. The case had an uneventful postoperative healing without dehiscence, infection and necrosis. We postulate that the primary closure of the site with buccal fat pad may ensure a sufficient blood supply and adequate protection for an effective bone-healing response to occur.

Keywords: buccal fat pad, oroantral communication, oral surgery, dehiscence

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Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

Abstract:

Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology

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