Search results for: generic drugs
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1468

Search results for: generic drugs

1198 Drug Susceptibility and Genotypic Assessment of Mycobacterial Isolates from Pulmonary Tuberculosis Patients in North East Ethiopia

Authors: Minwuyelet Maru, Solomon Habtemariam, Endalamaw Gadissa, Abraham Aseffa

Abstract:

Background: Tuberculosis is a major public health problem in Ethiopia. The burden of TB is aggravated by emergence and expansion of drug resistant tuberculosis and different lineages of Mycobacterium tuberculosis (M. tuberculosis) have been reported in many parts of the country. Describing strains of Mycobacterial isolates and drug susceptibility pattern is necessary. Method: Sputum samples were collected from smear positive pulmonary TB patients age >= 7 years between October 1, 2012 to September 30, 2013 and Mycobacterial strains isolated on Loweensten Jensen (LJ) media. Each strain was characterized by deletion typing and Spoligotyping. Drug sensitivity testing was determined with the indirect proportion method using Middle brook 7H10 media and association to determine possible risk factors to drug resistance was done. Result: A total of 144 smear positive pulmonary tuberculosis patients were enrolled. The age of participants ranged from 7 to 78 with mean age of 29.22 (±10.77) years. In this study 82.2% (n=97) of the isolates were sensitive to the four first line anti-tuberculosis drugs and resistance to any of the four drugs tested was 17.8% (n=21). A high frequency of any resistance was observed in isoniazid, 13.6%, (n=16) followed by streptomycin, 11.8% (n=14). No significant association of isoniazid resistance with HIV, sex and history of previous TB treatment was observed but there was significant association with age, high between 31-35 years of age (p=0.01). Majority, 89.9% (n=128) of participants were new cases and only 11.1% (n=16) had history of previous TB treatment. No MDR-TB from new cases and 2 MDRTB (13.3%) was isolated from re-treatment cases which was significantly associated with previous TB treatment (p<0.01). Thirty two different types of spoligotype patterns were identified and 74.1% were grouped in to 13 clusters. The dominant strains were SIT 25, 18.1% (n=21), SIT 53, 17.2% (n=20) and SIT 149, 8.6% (n=10). Lineage 4 is the predominant lineage followed by lineage 3 and lineage 7 comprising 65.5% (n=76), 28.4% (n=33) and 6% (n=7) respectively. Majority of strains from lineage 3 and 4 were SIT 25 (63.6%) and SIT 53 (26.3%) whereas SIT 343 was the dominant strain from lineage 7 (71.4%). Conclusion: Wide spread of lineage 3 and lineage 4 of the modern lineage and high number of strain cluster indicates high ongoing transmission. The high proportion resistance to any of the first line anti-tuberculosis drugs may be a potential source in the emergence of MDR-TB. Wide spread of SIT 25 and SIT 53 having a tendency of ease transmission and presence of higher resistance of isoniazid in working and mobile age group, 31-35 years of age may increase risk of drug resistant strains transmission.

Keywords: tuberculosis, drug susceptibility, strain diversity, lineage, Ethiopia, spoligotyping

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1197 Preparation, Characterization, and in-Vitro Drug Release Study of Methotrexate-Loaded Hydroxyapatite-Sodium Alginate Nanocomposites

Authors: Friday G. Okibe, Edit B. Agbaji, Victor O. Ajibola, Christain C. Onoyima

Abstract:

Controlled drug delivery systems reduce dose-dependent toxicity associated with potent drugs, including anticancer drugs. In this research, hydroxyapatite (HA) and hydroxyapatite-sodium alginate nanocomposites (HASA) were successfully prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The FTIR result showed absorption peaks characteristics of pure hydroxyapatite (HA), and also confirmed the chemical interaction between hydroxyapatite and sodium alginate in the formation of the composite. Image analysis from SEM revealed nano-sized hydroxyapatite and hydroxyapatite-sodium alginate nanocomposites with irregular morphologies. Particle size increased with the formation of the nanocomposites relative to pure hydroxyapatite, with no significant change in particles morphologies. Drug loading and in-vitro drug release study were carried out using synthetic body fluid as the release medium, at pH 7.4 and 37 °C and under perfect sink conditions. The result shows that drug loading is highest for pure hydroxyapatite and decreased with increasing quantity of sodium alginate. However, the release study revealed that HASA-5%wt and HASA-20%wt presented better release profile than pure hydroxyapatite, while HASA-33%wt and HASA-50%wt have poor release profiles. This shows that Methotrexate-loaded hydroxyapatite-sodium alginate if prepared under optimal conditions is a potential carrier for effective delivery of Methotrexate.

Keywords: drug-delivery, hydroxyapatite, methotrexate, nanocomposites, sodium alginate

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1196 Drug-Drug Plasma Protein Binding Interactions of Ivacaftor

Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

Abstract:

Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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1195 The Potential Role of Some Nutrients and Drugs in Providing Protection from Neurotoxicity Induced by Aluminium in Rats

Authors: Azza A. Ali, Abeer I. Abd El-Fattah, Shaimaa S. Hussein, Hanan A. Abd El-Samea, Karema Abu-Elfotuh

Abstract:

Background: Aluminium (Al) represents an environmental risk factor. Exposure to high levels of Al causes neurotoxic effects and different diseases. Vinpocetine is widely used to improve cognitive functions, it possesses memory-protective and memory-enhancing properties and has the ability to increase cerebral blood flow and glucose uptake. Cocoa bean represents a rich source of iron as well as a potent antioxidant. It can protect from the impact of free radicals, reduces stress as well as depression and promotes better memory and concentration. Wheatgrass is primarily used as a concentrated source of nutrients. It contains vitamins, minerals, carbohydrates, amino acids and possesses antioxidant and anti-inflammatory activities. Coenzyme Q10 (CoQ10) is an intracellular antioxidant and mitochondrial membrane stabilizer. It is effective in improving cognitive disorders and has been used as anti-aging. Zinc is a structural element of many proteins and signaling messenger that is released by neural activity at many central excitatory synapses. Objective: To study the role of some nutrients and drugs as Vinpocetine, Cocoa, Wheatgrass, CoQ10 and Zinc against neurotoxicity induced by Al in rats as well as to compare between their potency in providing protection. Methods: Seven groups of rats were used and received daily for three weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except for the control group which received saline. All groups of Al-toxicity model except one group (non-treated) were co-administered orally together with AlCl3 the following treatments; Vinpocetine (20mg/kg), Cocoa powder (24mg/kg), Wheat grass (100mg/kg), CoQ10 (200mg/kg) or Zinc (32mg/kg). Biochemical changes in the rat brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups besides histopathological examinations in different brain regions. Results: Neurotoxicity and neurodegenerations in the rat brain after three weeks of Al exposure were indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the significant decrease in SOD, TAC, BDNF and confirmed by the histopathological changes in the brain. On the other hand, co-administration of each of Vinpocetine, Cocoa, Wheatgrass, CoQ10 or Zinc together with AlCl3 provided protection against hazards of neurotoxicity and neurodegenerations induced by Al, their protection were indicated by the decrease in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the increase in SOD, TAC, BDNF and confirmed by the histopathological examinations of different brain regions. Vinpocetine and Cocoa showed the most pronounced protection while Zinc provided the least protective effects than the other used nutrients and drugs. Conclusion: Different degrees of protection from neurotoxicity and neuronal degenerations induced by Al could be achieved through the co-administration of some nutrients and drugs during its exposure. Vinpocetine and Cocoa provided the most protection than Wheat grass, CoQ10 or Zinc which showed the least protective effects.

Keywords: aluminum, neurotoxicity, vinpocetine, cocoa, wheat grass, coenzyme Q10, Zinc, rats

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1194 Post Coronary Artery Stenting Reflighting: Need for Change in Policy with Changing Antiplatelet Therapy

Authors: Keshavamurthy Ganapathy Bhat, Manvinderpal Singh Marwaha

Abstract:

Background: Coronary artery Disease (CAD) is a common cause of morbidity, mortality and reason for unfitness amongst aircrew. Coronary angioplasty and stenting are the standard of care for CAD. Antiplatelet drugs like Aspirin and Clopidogrel(Dual Antiplatelet therapy) are routinely prescribed post-stenting which are permitted for flying. However, in the recent past, Ticagrelor is being used in place of Clopidogrel as per ACC AHA and ESC guidelines. However Ticagrelor is not permitted for flying. Case Presentation: A 55-year-old pilot suffered Anterior Wall Myocardial Infarction. Angiography showed blockages in Left Anterior Descending Artery(LAD) and Right coronary artery (RCA). He underwent primary angioplasty and stenting LAD and subsequent stenting to RCA. Recovery was uneventful. One year later he was asymptomatic with normal Left ventricular function and no reversible perfusion defect on stress MPI. He had patent stents and coronaries on check angiogram. However, he was not allowed to fly since he was on Ticagrelor. He had to be switched over to Clopidogrel from Ticagrelor one year after stenting to permit him for flying. Similarly, switching had to be done in a 45-year-old pilot. Ticagrelor has been proven to be more effective than clopidogrel and as safe as Clopidogrel in preventing stent thrombosis. If Clopidogrel is being permitted, there is no need to restrict Ticagrelor. Hence "Policy" needs to be changed. Conclusions: Dual Antiplatelet therapy is the standard of care post coronary stenting which has been proved safe and effective. Policy needs to be changed to permit flying with Ticagrelor which is more effective than Clopidogrel and equally safe.

Keywords: antiplatelet drugs, coronary artery disease, stenting, ticagrelor

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1193 A Cros Sectional Observational Study of Prescription Pattern of Gastro-Protective Drugs with Non-Steroidal Anti-Inflammatory Drugs in Nilgiris, India

Authors: B.S. Roopa

Abstract:

Objectives: To investigate the prevalence of concomitant use of GPDs in patients treated with NSAIDs and GPDs in recommended dose and frequency as prophylaxis. And also to know the association between risk factors and prescription of GPDs in patients treated with NSAIDs. Methods: Study was a prospective, observational, cross-sectional survey. Data from patients with prescription of NSAIDs at the out-patient departments of secondary care Hospital, Nilgiris, India were collected in a specially designed proforma for a period of 45 days. Analysis using χ2 tests for discrete variables. Factors that might be associated with prescription of GPD with NSIADs were assessed in multiple logistic regression models. Results: Three hundred and three patients were included in this study, and the rate of GPD prescription was 89.1%. Most of the patients received H2-receptor antagonist, and, to a lesser degree, antacid and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much more likely to be co-prescribed GPD than those who had no history of GI disorders .Compared with patients who were managed in general outpatient clinic, those managed in Secondary care hospital in Nilgrisis, India were more likely to receive GPD. Conclusions: The prescription rate of GPD with NSAIDs is high. Patients were prescribed with H2RA with dose of 150mg twice daily, which are not effective in reducing the risk of NSAIDs induced gastric ulcer. Only the frequency of NSAIDs prescription was considered significant determinant for the co-prescription with GPAs in patients who are < 65 years and ≥ 65 years old.

Keywords: gastro protective agents, non steridol anti inlfammatory agents

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1192 Importance of Human Capital Development and Management in Industries

Authors: Birce Boga Bakirli

Abstract:

In this paper, we investigate ideas on human capital development and management in industries. We structured a model to be able to gather the data from the interviews conducted with worker, specialists and owners of companies. Different aspects of the situation are found in these interviews, and we used the information to model the benefit of the business owners and workers perspectives. These are modelled as a bi-level programming problem. Several instances of the generic cases are solved. The results show the importance of education within and out of the company for workers, and it returns for the company.

Keywords: bi-level programming, corporate strategy, cost tradeoffs, human capital, mixed integer programming, Stackelberg game, supplier relations, strategic planning

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1191 Hexahydropyrimidine-2,4-Diones: Synthesis and Cytotoxic Activity

Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

Abstract:

The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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1190 Maintaining Discipline in Tertiary Institutions in Nigeria

Authors: Ipenyi Peter

Abstract:

Discipline is an issue that tends to undermine the provision of quality education in tertiary institutions in Nigeria. This is because the overall goals of tertiary institutions, as enunciated in the National Policy of Education, can hardly be achieved by all the stakeholders without strict conformity and adherence to the rules and regulations and the ideals of the entire society. The adherence is essential for the general welfare of the society. This paper critically X-rayed the causes of indiscipline in tertiary institutions in Nigeria. Such courses include laxity in home control and parental supervision, school, teacher and societal factors as well as government influence. The paper recommended among others such strategies as enculturation, acculturation as well as the acquisition of a certain number of generic skills for dealing with discipline and ethical issues in tertiary institutions in Nigeria.

Keywords: discipline, education, tertiary institutions, society

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1189 Development and Test of an Open Source PX4 Controler for omnidirectional Unmanned Surface Vehicle

Authors: Norbert Szulc, Cezary Wieczorkowski, Igor Baranowski

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In this paper, a control system that bridges the gap in support for Unmanned Surface Vessels in the PX4 Opensource Autopilot was developed. The system is designed for an omnidirectional water craft with four motors. A modular autopilot architecture design centred around publish-subscribe interprocess communication was used. The paper presents the implementation and integration process of a generic surface vehicle controller capable of driving any configuration of motors through the recently introduced in control allocator in PX4 autopilot. The proposed approach was successfully tested in a case study through implementation on the ASV Perkoz.

Keywords: control system, PX4, drones, rovers, surface vessels, omnidirectional

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1188 Long-Term Economic-Ecological Assessment of Optimal Local Heat-Generating Technologies for the German Unrefurbished Residential Building Stock on the Quarter Level

Authors: M. A. Spielmann, L. Schebek

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In order to reach the long-term national climate goals of the German government for the building sector, substantial energetic measures have to be executed. Historically, those measures were primarily energetic efficiency measures at the buildings’ shells. Advanced technologies for the on-site generation of heat (or other types of energy) often are not feasible at this small spatial scale of a single building. Therefore, the present approach uses the spatially larger dimension of a quarter. The main focus of the present paper is the long-term economic-ecological assessment of available decentralized heat-generating (CHP power plants and electrical heat pumps) technologies at the quarter level for the German unrefurbished residential buildings. Three distinct terms have to be described methodologically: i) Quarter approach, ii) Economic assessment, iii) Ecological assessment. The quarter approach is used to enable synergies and scaling effects over a single-building. For the present study, generic quarters that are differentiated according to significant parameters concerning their heat demand are used. The core differentiation of those quarters is made by the construction time period of the buildings. The economic assessment as the second crucial parameter is executed with the following structure: Full costs are quantized for each technology combination and quarter. The investment costs are analyzed on an annual basis and are modeled with the acquisition of debt. Annuity loans are assumed. Consequently, for each generic quarter, an optimal technology combination for decentralized heat generation is provided in each year of the temporal boundaries (2016-2050). The ecological assessment elaborates for each technology combination and each quarter a Life Cycle assessment. The measured impact category hereby is GWP 100. The technology combinations for heat production can be therefore compared against each other concerning their long-term climatic impacts. Core results of the approach can be differentiated to an economic and ecological dimension. With an annual resolution, the investment and running costs of different energetic technology combinations are quantified. For each quarter an optimal technology combination for local heat supply and/or energetic refurbishment of the buildings within the quarter is provided. Coherently to the economic assessment, the climatic impacts of the technology combinations are quantized and compared against each other.

Keywords: building sector, economic-ecological assessment, heat, LCA, quarter level

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1187 Effects of Sacubitril and Valsartan on Gut Microbiome

Authors: Wei-Ju Huang, Hung-Pin Hsu

Abstract:

[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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1186 Oral Administration of Azithromycin Ameliorates Trypanosomosis in Trypanosoma congolense and T. Brucei Brucei Infected Mice

Authors: Nthatisi I. Molefe-Nyembe, Keisuke Suganuma, Oriel M. M. Thekisoe, Xuan Xuenan, Noboru Inoue

Abstract:

African trypanosomosis is a devastating disease of animals caused by parasites of the genus Trypanosoma negatively affecting the economic status of more than 36 African countries. Few available drugs for the treatment of trypanosomosis remain inaccessible in remote areas, are associated with severe toxicity and most importantly, resistance has widely developed against their usage. Therefore, safe, effective and easily administrable drugs are urgently in need. The objective of the current study was to determine efficacy of azithromycin (AZM), on T. congolense, T. brucei brucei in vitro and in vivo. A 96 well luciferase assay was conducted to determine the trypanocidal effect of AZM on T. congolense, T. b. brucei and T. evansi as well as the cytotoxicity effect on the MDBK and NIH 3T3 cells. Additionally, TEM analysis was conducted to determine the morphological alteration on the AZM treated samples. Mice were infected with T. congolense and T. b. brucei and orally treated with AZM for 7 and 28 days referred to as the short and the long-term treatment. The in vitro IC50 values of AZM on T. congolense, T. b. brucei and T. evansi was 0.19 ± 0.17; 3.69 ± 2.26 and 1.81 ± 1.82 μg/mL, respectively, while the cytotoxicity effects values were greater than 25 μg/mL. A vacuole-like structure was observed in the TEM imaging of AZM treated T. congolense, while the presence of glycosomes and acidocalcisome-like structured were detected in T. b. brucei samples. In vivo, AZM was more effective against T. congolense infected mice than T. b. brucei. In conclusion, AZM exhibited the trypanocidal effects on T. congolense and T. b. brucei infected mice. However, further studies are necessary to determine the metabolic pathway responsible for the observed efficacy.

Keywords: animal trypanosomosis, azithromycin, oral administration, trypanosoma congolense

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1185 Wind Energy Resources Assessment and Micrositting on Different Areas of Libya: The Case Study in Darnah

Authors: F. Ahwide, Y. Bouker, K. Hatem

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This paper presents long term wind data analysis in terms of annual and diurnal variations at different areas of Libya. The data of the wind speed and direction are taken each ten minutes for a period, at least two years, are used in the analysis. ‘WindPRO’ software and Excel workbook were used for the wind statistics and energy calculations. As for Derna, average speeds are 10 m, 20 m, and 40 m, and respectively 6.57 m/s, 7.18 m/s, and 8.09 m/s. Highest wind speeds are observed at SSW, followed by S, WNW and NW sectors. Lowest wind speeds are observed between N and E sectors. Most frequent wind directions are NW and NNW. Hence, wind turbines can be installed against these directions. The most powerful sector is NW (29.4 % of total expected wind energy), followed by 19.9 % SSW, 11.9% NNW, 8.6% WNW and 8.2% S. Furthermore in Al-Maqrun: the most powerful sector is W (26.8 % of total expected wind energy), followed by 12.3 % WSW and 9.5% WNW. While in Goterria: the most powerful sector is S (14.8 % of total expected wind energy), followed by SSE, SE, and WSW. And Misalatha: the most powerful sector is S, by far represents 28.5% of the expected power, followed by SSE and SE. As for Tarhuna, it is by far SSE and SE, representing each one two times the expected energy of the third powerful sector (NW). In Al-Asaaba: it is SSE by far represents 50% of the expected power, followed by S. It can to be noted that the high frequency of the south direction winds, that come from the desert could cause a high frequency of dust episodes. This fact then, should be taken into account in order to take appropriate measures to prevent wind turbine deterioration. In Excel workbook, an estimation of annual energy yield at position of Derna, Al-Maqrun, Tarhuna, and Al-Asaaba meteorological mast has been done, considering a generic wind turbine of 1.65 MW. (mtORRES, TWT 82-1.65MW) in position of meteorological mast. Three other turbines have been tested. At 80 m, the estimation of energy yield for Derna, Al-Maqrun, Tarhuna, and Asaaba is 6.78 GWh or 3390 equivalent hours, 5.80 GWh or 2900 equivalent hours, 4.91 GWh or 2454 equivalent hours and 5.08 GWh or 2541 equivalent hours respectively. It seems a fair value in the context of a possible development of a wind energy project in the areas, considering a value of 2400 equivalent hours as an approximate limit to consider a wind warm economically profitable. Furthermore, an estimation of annual energy yield at positions of Misalatha, Azizyah and Goterria meteorological mast has been done, considering a generic wind turbine of 2 MW. We found that, at 80 m, the estimation of energy yield is 3.12 GWh or 1557 equivalent hours, 4.47 GWh or 2235 equivalent hours and 4.07GWh or 2033 respectively . It seems a very poor value in the context of possible development of a wind energy project in the areas, considering a value of 2400 equivalent hours as an approximate limit to consider a wind warm economically profitable. Anyway, more data and a detailed wind farm study would be necessary to draw conclusions.

Keywords: wind turbines, wind data, energy yield, micrositting

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1184 Efficacy of Comprehensive Diabetic Care Program with the Reduction of HbA1c in Overweight Type II Diabetes Mellitus Patients: A Retrospective Study

Authors: Rohit Sane, Pravin Ghadigaonkar, Purvi Ahuja, Suvarna Tirmare, Archana Kelhe, Kranti Shinde, Rahul Mandole

Abstract:

To evaluate the efficacy of Comprehensive Diabetic Care Program with the reduction of HbA1c in overweight Diabetes Mellitus Type II patients retrospectively. Methods: Retrospective study was carried out on 34 overweight type II diabetic patients (Mean Age = 54.58 ±11.38 yrs). A total of 34 patients were enrolled after screening of 68 patients (HbA1c 7-10%). The patients were on concomitant drugs namely insulin (11.76%), DPP-4 inhibitor (17.64%), Biguanide (55.88%), Sulfonylurea (52.94%), thiazolidinedione (11.76%), other medications (20.58%) and no allopathic medications (14.70%). The patients were given Comprehensive Diabetic Care Program consisting of panchkarma procedures namely snehana (external oleation), swedana (passive heat therapy) and basti (enema), which was completed in 15 sittings. During the therapy and next 90 days, the patients followed low carbohydrate and moderate protein & fat diet. The primary endpoint of this study was the evaluation of reduction in HbA1c at the end of the follow-up after 90 days. Results: Thirty-four overweight type II diabetic patients (mean age: 54.58[±11.38], HbA1c[7-10%], 67.64% male and 32.35% female) were enrolled in the study. A significant reduction was observed in HbA1c levels (14.30%, p<0.05) at the end of the 90 days follow-up as compared to baseline. Also, BMI was reduced by 5.87%. There was reduction in the usage of the concomitant drugs namely insulin (2.94%), DPP-4 inhibitor (2.94%), Biguanide (32.35%), Sulfonylurea (35.29%), thiazolidinedione (5.88%), other medications(17.64%) and no allopathic medications (32.35%). Conclusion: The results of the study highlight not only in the reduction of HbA1c, but also in BMI and drug tapering of the CDC program in the overweight type II diabetic patients with HbA1c (7-10%).

Keywords: HbA1c, low carb diet, Panchakarma therapy, Type II Diabetes

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1183 Evaluation of Gingival Hyperplasia Caused by Medications

Authors: Ilma Robo, Saimir Heta, Greta Plaka, Vera Ostreni

Abstract:

Purpose: Drug gingival hyperplasia is an uncommon pathology encountered during routine work in dental units. The purpose of this paper is to present the clinical appearance of gingival hyperplasia caused by medications. There are already three classes of medications that cause hyperplasia and based on data from the literature, the clinical cases encountered and included in this study have been compared. Materials and Methods: The study was conducted in a total of 311 patients, out of which 182 patients were included in our study, meeting the inclusion criteria. After each patient's history was recorded and it was found that patients were in their knowledge of chronic illness, undergoing treatment of gingivitis hypertrophic drugs was performed with a clinical examination of oral cavity and assessment by vertical and horizontal evaluation according to the periodontal indexes. Results: Of the data collected during the study, it was observed that 97% of patients with gingival hyperplasia are treated with nifedipine. 84% of patients treated with selected medicines and gingival hyperplasia in the oral cavity has been exposed at time period for more than 1 year and 1 month. According to the GOI, in the first rank of this index are about 21% of patients, in the second rank are 52%, in the third rank are 24% and in the fourth grade are 3%. According to the horizontal growth index of gingival hyperplasia, grade 1 included about 61% of patients and grade 2 included about 39% of patients with gingival hyperplasia. Bacterial index divides patients by degrees: grading 0 - 8.2%, grading 1 - 32.4%, grading 2 - 14% and grading 3 - 45.1%. Conclusions: The highest percentage of gingival hyperplasia caused by drugs is due to dosing of nifedipine for a duration of dosing and application for systemic healing for more than 1 year.

Keywords: drug gingival hyperplasia, horizontal growth index, vertical growth index

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1182 Practical Techniques of Improving State Estimator Solution

Authors: Kiamran Radjabli

Abstract:

State Estimator became an intrinsic part of Energy Management Systems (EMS). The SCADA measurements received from the field are processed by the State Estimator in order to accurately determine the actual operating state of the power systems and provide that information to other real-time network applications. All EMS vendors offer a State Estimator functionality in their baseline products. However, setting up and ensuring that State Estimator consistently produces a reliable solution often consumes a substantial engineering effort. This paper provides generic recommendations and describes a simple practical approach to efficient tuning of State Estimator, based on the working experience with major EMS software platforms and consulting projects in many electrical utilities of the USA.

Keywords: convergence, monitoring, state estimator, performance, troubleshooting, tuning, power systems

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1181 Towards a Goal-Question-Metric Based Approach to Assess Social Sustainability of Software Systems

Authors: Rahma Amri, Narjès Bellamine Ben Saoud

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Sustainable development or sustainability is one of the most urgent issues in actual debate in almost domains. Particularly the significant way the software pervades our live should make it in the center of sustainability concerns. The social aspects of sustainability haven’t been well studied in the context of software systems and still immature research field that needs more interest among researchers’ community. This paper presents a Goal-Question-Metric based approach to assess social sustainability of software systems. The approach is based on a generic social sustainability model taken from Social sciences.

Keywords: software assessment approach, social sustainability, goal-question-metric paradigm, software project metrics

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1180 Critical Core Skills Profiling in the Singaporean Workforce

Authors: Bi Xiao Fang, Tan Bao Zhen

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Soft skills, core competencies, and generic competencies are exchangeable terminologies often used to represent a similar concept. In the Singapore context, such skills are currently being referred to as Critical Core Skills (CCS). In 2019, SkillsFuture Singapore (SSG) reviewed the Generic Skills and Competencies (GSC) framework that was first introduced in 2016, culminating in the development of the Critical Core Skills (CCS) framework comprising 16 soft skills classified into three clusters. The CCS framework is part of the Skills Framework, and whose stated purpose is to create a common skills language for individuals, employers and training providers. It is also developed with the objectives of building deep skills for a lean workforce, enhance business competitiveness and support employment and employability. This further helps to facilitate skills recognition and support the design of training programs for skills and career development. According to SSG, every job role requires a set of technical skills and a set of Critical Core Skills to perform well at work, whereby technical skills refer to skills required to perform key tasks of the job. There has been an increasing emphasis on soft skills for the future of work. A recent study involving approximately 80 organizations across 28 sectors in Singapore revealed that more enterprises are beginning to recognize that soft skills support their employees’ performance and business competitiveness. Though CCS is of high importance for the development of the workforce’s employability, there is little attention paid to the CCS use and profiling across occupations. A better understanding of how CCS is distributed across the economy will thus significantly enhance SSG’s career guidance services as well as training providers’ services to graduates and workers and guide organizations in their hiring for soft skills. This CCS profiling study sought to understand how CCS is demanded in different occupations. To achieve its research objectives, this study adopted a quantitative method to measure CCS use across different occupations in the Singaporean workforce. Based on the CCS framework developed by SSG, the research team adopted a formative approach to developing the CCS profiling tool to measure the importance of and self-efficacy in the use of CCS among the Singaporean workforce. Drawing on the survey results from 2500 participants, this study managed to profile them into seven occupation groups based on the different patterns of importance and confidence levels of the use of CCS. Each occupation group is labeled according to the most salient and demanded CCS. In the meantime, the CCS in each occupation group, which may need some further strengthening, were also identified. The profiling of CCS use has significant implications for different stakeholders, e.g., employers could leverage the profiling results to hire the staff with the soft skills demanded by the job.

Keywords: employability, skills profiling, skills measurement, soft skills

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1179 Lean Models Classification: Towards a Holistic View

Authors: Y. Tiamaz, N. Souissi

Abstract:

The purpose of this paper is to present a classification of Lean models which aims to capture all the concepts related to this approach and thus facilitate its implementation. This classification allows the identification of the most relevant models according to several dimensions. From this perspective, we present a review and an analysis of Lean models literature and we propose dimensions for the classification of the current proposals while respecting among others the axes of the Lean approach, the maturity of the models as well as their application domains. This classification allowed us to conclude that researchers essentially consider the Lean approach as a toolbox also they design their models to solve problems related to a specific environment. Since Lean approach is no longer intended only for the automotive sector where it was invented, but to all fields (IT, Hospital, ...), we consider that this approach requires a generic model that is capable of being implemented in all areas.

Keywords: lean approach, lean models, classification, dimensions, holistic view

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1178 Development of the Drug Abuse Health Information System in Thai Community

Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Sivaporn Aungwattana, Decha Tamdee, Wongamporn Pinyavong

Abstract:

Drug addiction represents one of the most important public health issues in both developed and developing countries. The purpose of this study was to develop a drug abuse health information in a community in Northern Thailand using developmental research design. The developmental researchers performed four phases to develop drug abuse health information, including 1) synthesizing knowledge related to drug abuse prevention and identifying the components of drug abuse health information; 2) developing the system in mobile application and website; 3) implementing drug abuse health information in the rural community; and 4) evaluating the feasibility of drug abuse health information. Data collection involved both qualitative and quantitative procedures. The qualitative data and quantitative data were analyzed using content analysis and descriptive statistics, respectively. The findings of this study showed that drug abuse health information consisted of five sections, including drug-related prevention knowledge for teens, drug-related knowledge for adults and professionals, the database for drug dependence treatment centers, self-administered questionnaires, and supportive counseling sections. First, in drug-related prevention knowledge for teens, the developmental researchers designed four infographics and animation to provide drug-related prevention knowledge, including types of illegal drugs, causes of drug abuse, consequences of drug abuse, drug abuse diagnosis and treatment, and drug abuse prevention. Second, in drug-related knowledge for adults and professionals, the developmental researchers developed many documents in a form of PDF file to provide drug-related knowledge, including types of illegal drugs, causes of drug abuse, drug abuse prevention, and relapse prevention guideline. Third, database for drug dependence treatment centers included the place, direction map, operation time, and the way for contacting all drug dependence treatment centers in Thailand. Fourth, self-administered questionnaires comprised preventive drugs behavior questionnaire, drug abuse knowledge questionnaire, the stages of change readiness and treatment eagerness to drug use scale, substance use behaviors questionnaire, tobacco use behaviors questionnaire, stress screening, and depression screening. Finally, for supportive counseling, the developmental researchers designed chatting box through which each user could write and send their concerns to counselors individually. Results from evaluation process showed that 651 participants used drug abuse health information via mobile application and website. Among all users, 48.8% were males and 51.2% were females. More than half (55.3%) were 15-20 years old and most of them (88.0%) were Buddhists. Most users reported ever getting knowledge related to drugs (86.1%), and drinking alcohol (94.2%) while some of them (6.9%) reported ever using tobacco. For satisfaction with using the drug abuse health information, more than half of users reflected that the contents of drug abuse health information were interesting (59%), up-to date (61%), and highly useful to their self-study (59%) at high level. In addition, half of them were satisfied with the design in terms of infographics (54%) and animation (51%). Thus, this drug abuse health information can be adopted to explore drug abuse situation and serves as a tool to prevent drug abuse and addiction among Thai community people.

Keywords: drug addiction, health informatics, big data, development research

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1177 A Reduced Distributed Sate Space for Modular Petri Nets

Authors: Sawsen Khlifa, Chiheb AMeur Abid, Belhassan Zouari

Abstract:

Modular verification approaches have been widely attempted to cope with the well known state explosion problem. This paper deals with the modular verification of modular Petri nets. We propose a reduced version for the modular state space of a given modular Petri net. The new structure allows the creation of smaller modular graphs. Each one draws the behavior of the corresponding module and outlines some global information. Hence, this version helps to overcome the explosion problem and to use less memory space. In this condensed structure, the verification of some generic properties concerning one module is limited to the exploration of its associated graph.

Keywords: distributed systems, modular verification, petri nets, state space explosition

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1176 Antibacterial Effect of Hydroalcoholic Extract of Salvia Officinalis and, Mentha Pulegium on Three Strains of Streptococcus Mutants, Lactobacillus Rhamnosus and, Actinomyces Viscosus Dental Caries in-vitro

Authors: H. Nabahat, E. Amiri, F. AzaditalabDavoudabadi, N. Zaeri

Abstract:

Tooth decay is one of the most common forms of oral and dental illness in the world, which causes huge costs of treatment, especially in high-risk groups such as people with oral dry mouth, prevention and control of it are very important. The use of traditional treatments such as extraction of drugs from medicinal plants is of paramount importance to Iran and the international community as well. The present study was conducted with the aim of investigating the antibacterial effect of the extract of Salvia officinalis and Mentha pulegium, which are the most commonly used drugs in the treatment of oral and teeth bacterial (Streptococcus mutant, Lactobacillus rhamnosis, and Actinomyces viscosis) in vitro method. In this experimental study, two herbs of Salvia and Mentha were prepared by maceration of hydroalcoholic extract, and the antibacterial effect was evaluated by broth macro dilution on streptococcal mutagen bacteria, lactobacillus rhamnosis, and viscose actinomycosis. The results were analyzed by the Whitney Mann test (P > 0.05). The results showed that the minimum inhibitory concentration (MIC) of the salmonella extract for Streptococcus mutan were 6.25 and 12.5 μg/ml, respectively, for lactobacillus of 1.56 and 3.12 μg/ml, respectively, and for actinomycosis viscose, The order of 12.5 and 100 μg/ml was obtained. As a result, broth macro dilution showed that both extracts of Salvia and Mentha had an inhibitory effect on all three species of bacteria. This effect for Salvia was significantly (P < 0.05) more than Mentha and was within the concentration range of both the extracts and had a bactericidal effect on all three bacteria.

Keywords: antibacterial effect, dental bacteria, herbal extracts , salvia officinalis, mentha pulegium

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1175 DPAGT1 Inhibitors: Discovery of Anti-Metastatic Drugs

Authors: Michio Kurosu

Abstract:

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

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

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1174 Hybrid-Nanoengineering™: A New Platform for Nanomedicine

Authors: Mewa Singh

Abstract:

Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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1173 A Computational Study Concerning the Biological Effects of the Most Commonly Used Phthalates

Authors: Dana Craciun, Daniela Dascalu, Adriana Isvoran

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Phthalates are a class of plastic additives that are used to enhance the physical properties of plastics and as solvents in paintings and some of them proved to be of particular concern for the human health. There are insufficient data concerning the health risks of phthalates and further research on evaluating their effects in humans is needed. As humans are not volunteers for such experiments, computational analysis may be used to predict the biological effects of phthalates in humans. Within this study we have used some computational approaches (SwissADME, admetSAR, FAFDrugs) for predicting the absorption, distribution, metabolization, excretion and toxicity (ADME-Tox) profiles and pharmacokinetics for the most common used phthalates. These computational tools are based on quantitative structure-activity relationship modeling approach. The predictions are further compared to the known effects of each considered phthalate in humans and correlations between computational results and experimental data are discussed. Our data revealed that phthalates are a class of compounds reflecting high toxicity both when ingested and when inhaled, but by inhalation their toxicity is even greater. The predicted harmful effects of phthalates are: toxicity and irritations of the respiratory and gastrointestinal tracts, dyspnea, skin and eye irritations and disruption of the functions of liver and of the reproductive system. Many of investigated phthalates are predicted to be able to inhibit some of the cytochromes involved in the metabolism of numerous drugs and consequently to affect the efficiency of administrated treatments for many diseases and to intensify the adverse drugs reactions. The obtained predictions are in good agreement with clinical data concerning the observed effects of some phthalates in cases of acute exposures. Our study emphasizes the possible health effects of numerous phthalates and underlines the applicability of computational methods for predicting the biological effects of xenobiotics.

Keywords: phthalates, ADME-Tox, pharmacokinetics, biological effects

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1172 An Analysis of Legal and Ethical Implications of Sports Doping in India

Authors: Prathyusha Samvedam, Hiranmaya Nanda

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Doping refers to the practice of using drugs or practices that enhance an athlete's performance. This is a problem that occurs on a worldwide scale and compromises the fairness of athletic tournaments. There are rules that have been created on both the national and international levels in order to prevent doping. However, these rules sometimes contradict one another, and it is possible that they don't do a very good job of prohibiting people from using PEDs. This study will contend that India's inability to comply with specific Code criteria, as well as its failure to satisfy "best practice" standards established by other countries, demonstrates a lack of uniformity in the implementation of anti-doping regulations and processes among nations. Such challenges have the potential to undermine the validity of the anti-doping system, particularly in developing nations like India. This article on the legislative framework in India governing doping in sports is very important. To begin, doping in sports is a significant problem that affects the spirit of fair play and sportsmanship. Moreover, it has the potential to jeopardize the integrity of the sport itself. In addition, the research has the potential to educate policymakers, sports organizations, and other stakeholders about the current legal framework and how well it discourages doping in athletic competitions. This article is divided into four distinct sections. The first section offers an explanation of what doping is and provides some context about its development throughout time. Followed the role of anti-doping authorities and the responsibilities they perform are investigated. Case studies and the research technique that will be employed for the study are in the third section; finally, the results are presented in the last section. In conclusion, doping is a severe problem that endangers the honest competition that exists within sports.

Keywords: sports law, doping, NADA, WADA, performance enhancing drugs, anti-doping bill 2022

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1171 Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder

Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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1170 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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1169 The Gold Standard Treatment Plan for Vitiligo: A Review on Conventional and Updated Treatment Methods

Authors: Kritin K. Verma, Brian L. Ransdell

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White patches are a symptom of vitiligo, a chronic autoimmune dermatological condition that causes a loss of pigmentation in the skin. Vitiligo can cause issues of self-esteem and quality of life while also progressing the development of other autoimmune diseases. Current treatments in allopathy and homeopathy exist; some treatments have been found to be toxic, whereas others have been helpful. Allopathy has seemed to offer several treatment plans, such as phototherapy, skin lightening preparations, immunosuppressive drugs, combined modality therapy, and steroid medications to improve vitiligo. This presentation will review the FDA-approved topical cream, Opzelura, a JAK inhibitor, and its effects on limiting vitiligo progression. Meanwhile, other non-conventional methods, such as Arsenic Sulphuratum Flavum used in homeopathy, will be debunked based on current literature. Most treatments still serve to arrest progression and induce skin repigmentation. Treatment plans may differ between patients due to depigmentation location on the skin. Since there is no gold standard plan for treating patients with vitiligo, the oral presentation will review all topical and systemic pharmacological therapies that fight the depigmentation of the skin and categorize their validity from a systematic review of the literature. Since treatment plans are limited in nature, all treatment methods will be mentioned and an attempt will be made to make a golden standard treatment process for these patients.

Keywords: vitiligo, phototherapy, immunosuppressive drugs, skin lightening preparations, combined modality therapy, arsenic sulphuratum flavum, homeopathy, allopathy, golden standard, Opzelura

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