Search results for: drug susceptibility

Authors: Janneth Gonzalez, Marco Avila, George Barreto

Abstract:

GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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Authors: Satendra Pal Singh, Dalip Kr. Kakru, Jyoti Mishra, Rajesh Thakur, Tarana Sarwat

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COVID-19 is still an intrigue as far as morbidity or mortality is concerned. The rate of recovery varies from person to person, & it depends upon the accessibility of the healthcare system and the roles played by the physicians and caregivers. It is envisaged that with the passage of time, people would become immune to this virus, and those who are vulnerable would sustain themselves with the help of vaccines. The proposed study deals with the severeness of COVID-19 is associated with some specific biomarkers linked to correlate age and gender. We will be assessing the overall homeostasis of the persons who were affected by the coronavirus infection and also of those who recovered from it. Some people show more severe effects, while others show very mild symptoms, however, they show low CT values. Thus far, it is unclear why the new strain of Covid has different effects on different people in terms of age, gender, and ABO blood typing. According to data, the fatality rate with heart disease was 10.5 percent, 7.3 percent were diabetic, and 6 percent who are already infected from other comorbidities. However, some COVID-19 cases are worse than others & it is not fully explainable as of date. Overall data show that the ABO blood group is effective or prone to the risk of SARS-COV2 infection, while another study also shows the phenotypic effects of the blood group related to covid. It is an accepted fact that females have more strong immune systems than males, which may be related to the fact that females have two ‘X’ chromosomes, which might contain a more effective immunity booster gene on the X chromosome, and are capable to protect the female. Also specific sex hormones also induce a better immune response in a specific gender. This calls for in-depth analysis to be able to gain insight into this dilemma. COVID-19 is still not fully characterized, and thus we are not very familiar with its biology, mode of infection, susceptibility, and overall viral load in the human body. How many virus particles are needed to infect a person? How, then, comorbidity contribute to coronavirus infection? Since the emergence of this virus in 2020, a large number of papers have been published, and seemingly, vaccines have been prepared. But still, a large number of questions remain unanswered. The proneness of humans for infection by covid-19 needs to be established to be able to develop a better strategy to fight this virus. Our study will be on the Impact of demography on the Severity of covid-19 infection & at the same time, will look into gender-specific sensitivity of Covid-19 and the Operational variation of different biochemical markers in Covid-19 positive patients. Besides, we will be studying the co-relation, if any, of COVID severity & ABO Blood group type and the occurrence of the most common blood group type amongst positive patience.

Keywords: coronavirus, ABO blood group, age, gender

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Authors: Atena Naeimi, Mehri-Sadat Ekrami-Kakhki

Abstract:

Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 have received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials. Fe3O4–ZnO nanostructures were synthesized via a surfactant-free ultrasonic reaction at room temperatures. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite 1 g of Fe3O4 nanostructures were dispersed in 100 mL of distilled water. 0.25 g of Zn (NO3)2 and 20 mL of NH3 solution 1 M were then slowly added to the solution under ultrasonic irradiation. The product was centrifuged, washed with distilled water and dried in the air. The photocatalytic behaviour of Fe3O4–ZnO nanoparticles was evaluated using the degradation of a methyl orange aqueous solution under ultraviolet light irradiation. As time increased, more and more methyl orange was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The methyl orange concentration decreased rapidly with increasing UV-irradiation time.

Keywords: nanocomposite, ultrasonic, paramagnetic, photocatalytic

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Authors: Neda Gegar Goshe, Hossein Rassi

Abstract:

The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The biotransformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose .This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.

Keywords: Streptomyces fradiae, eryK and eryG genes, tylosin, antibiotics

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Authors: Katya E. Manalastas

Abstract:

This thesis is a dialogue with Freud about vulnerability and any forms of transience we encounter in life. This study argues that Freud’s Ethics of Finitude, which is framed within the psychoanalytic context, is a critical theory about how human beings fail to become what they are because of their attachment to their illusions—to their visions of perfection and immortality. Freud’s Ethics of Finitude positions itself between our detachment to ideals and recognition of our own death through our loved one. His texts portray the predicament of the finite individual who suffers from feelings of guilt and anxiety because of his failure to live up to the demands of his idealistic civilized society. The civilized society has overestimated men’s susceptibility to culture. It imposes excessive sublimation, conformity to rigid moral ideals, and instinctive repression to manage human aggression. However, by doing this, civilization becomes a main source of men’s suffering. The lack of instinctive freedom will result in a community of tamed but unhappy people. Civilization has also constructed theories and measures to rule out death and pain from the realities of life. Therefore, a man lives his life repressing his instincts and ignorant of his own mortality. For Freud, war and neurosis are just few of the consequences of a civilization that imprisons the individual from cultural hypocrisy instead of giving more play to truthfulness. The occurrence of Great War destroyed our pride in the attainments of civilization and let loose the hostile impulses within us which we thought had been totally eradicated by means of instinctive repression and sublimation. War destroyed most of the things that we had loved and showed us the impermanence of all the things that we had deemed perfect and everlasting. This chaotic event also revealed the damaging impact of our attachment to past values that no longer bind us; our futile attempts to escape suffering; and our refusal to confront the painfulness of loss and mourning. With this given backdrop, this study launches Freud’s Ethics of Finitude—which culminates not in the submission of an individual to the unquestioned authority nor in the blind optimism and love for illusory happiness but in the pedagogy of mourning which brings forth the authentic education of man towards the truth about himself. His Ethics of Finitude is a form of labor in and through which the individual steps out of the realm of illusions and ideals that hinder him to confront his imperfections and accept the difficulties of existence. Through his analysis of the Great War, Freud seeks to awaken in us our ability to evaluate the way we see ourselves and to live our lives with death in mind. His Ethics of Finitude leads us to the fulfillment of our first duty as a living being, which is to endure life. We can only endure life if we are prepared to die and let go.

Keywords: critical theory, ethics of finitude, psychoanalysis, Sigmund Freud

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Authors: Harshani Uggallage, Kapila D. Dissanayaka

Abstract:

A Sulforhodamine-B assay-guided fractionation on Nigella sativa seeds was conducted to determine the presence of cytotoxic compounds against human hepatoma (HepG2) cells. Initially, a freeze-dried sample of Nigella sativa seeds was sequentially extracted into solvents of increasing polarities. Crude extracts from the sequential extraction of Nigella sativa seeds in chloroform and ethyl acetate showed the highest cytotoxicity. The combined mixture of these two extracts was subjected to bioassay guided fractionation using a modified Kupchan method of partitioning, followed by Sephadex® LH-20 chromatography. This chromatographic separation process resulted in a column fraction with a convincing IC50 (half-maximal inhibitory concentration) value of 13.07µg/ml, which is considerable for developing therapeutic drug leads against human hepatoma. Reversed phase High-Performance Liquid Chromatography (HPLC) was finally conducted for the same column fraction, and the result indicates the presence of one or several main cytotoxic compounds against human HepG2 cells.

Keywords: cytotoxic compounds, half-maximal inhibitory concentration, high-performance liquid chromatography, human HepG2 cells, nigella sativa seeds, Sulforhodamine-B assay

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Authors: Patsorn Worawattananutai, Srisopa Ruangnoo, Arunporn Itharat

Abstract:

Hibiscus sabdariffa (HS) leaves are vegetables which are extensively used as blood tonic and laxatives in Thai traditional medicine. They are popularly used as healthy sour soup for prevention of chronic diseases such as cancer. Therefore, the cytotoxic activity of different extracts of fresh and dried Hibiscus sabdariffa leaves were investigated via the sulforhodamine B (SRB) assay against three types of women’s cancer cell lines, namely the human cervical adenocarcinoma cell line (HeLa), the human ovarian adenocarcinoma cell line (SKOV-3), and the human breast adenocarcinoma cell line (MCF-7). Extraction methods were squeezing, boiling with water and maceration with 95% or 50% ethanol. The 95% ethanolic extracts of Hibiscus sabdariffa dry leaves (HSDE95) showed the highest cytotoxicity against all types of women’s cancer cell lines with the IC50 values in range 7.51±0.33 to 12.13±1.85 µg/ml. Its IC50 values against SKOV-3, HeLa and MCF-7 were 7.51±0.33, 9.44±1.41 and 12.13±1.85 µg/ml, respectively. In these results, this extract can be classified as “active” according to the NCI guideline which indicated that IC50 values of the active cytotoxic plant extracts have to be beneath 20 µg/ml. Thus, HSDE95 was concluded to be a potent cytotoxic drug for all women’s cancer cells. This extract should be further investigated to isolate active compounds against women’s cancer cells.

Keywords: breast adenocarcinoma, cervical adenocarcinoma, cytotoxic activity, Hibiscus sabdariffa, ovarian adenocarcinoma

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Authors: Arti Bagada, Kantilal Vadalia, Mihir Raval

Abstract:

Cilnidipine is practically insoluble in water which results in its insufficient oral bioavailability. The purpose of the present investigation was to formulate cilnidipine nanoparticles by nanoprecipitation method to increase the aqueous solubility and dissolution rate and hence bioavailability by utilizing various experimental statistical design modules. Experimental design were used to investigate specific effects of independent variables during preparation cilnidipine nanoparticles and corresponding responses in optimizing the formulation. Plackett Burman design for independent variables was successfully employed for optimization of nanoparticles of cilnidipine. The influence of independent variables studied were drug concentration, solvent to antisolvent ratio, polymer concentration, stabilizer concentration and stirring speed. The dependent variables namely average particle size, polydispersity index, zeta potential value and saturation solubility of the formulated nanoparticles of cilnidipine. The experiments were carried out according to 13 runs involving 5 independent variables (higher and lower levels) employing Plackett-Burman design. The cilnidipine nanoparticles were characterized by average particle size, polydispersity index value, zeta potential value and saturation solubility and it results were 149 nm, 0.314, 43.24 and 0.0379 mg/ml, respectively. The experimental results were good correlated with predicted data analysed by Plackett-Burman statistical method.

Keywords: dissolution enhancement, nanoparticles, Plackett-Burman design, nanoprecipitation

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Authors: Taruna Katyal Arora, Geeta Kumari, Hari Shankar, Neelima Mishra

Abstract:

Substandard and counterfeit antimalarials is a major problem in malaria endemic areas. The availability of counterfeit/ substandard medicines is not only decreasing the efficacy in patients, but it is also one of the contributing factors for developing antimalarial drug resistance. Owing to this, a pilot study was conducted to survey quality of drugs collected from different malaria endemic areas of India. Artesunate+Sulphadoxine-Pyrimethamine (AS+SP), Artemether-Lumefantrine (AL), Chloroquine (CQ) tablets were randomly picked from public health facilities in selected states of India. The quality of antimalarial drugs from these areas was assessed by using Global Pharma Health Fund Minilab test kit. This includes physical/visual inspection and disintegration test. Thin-layer chromatography (TLC) was carried out for semi-quantitative assessment of active pharmaceutical ingredients. A total of 45 brands, out of which 21 were for CQ, 14 for AL and 10 for AS+SP were tested from Uttar Pradesh (U.P.), Mizoram, Meghalaya and Gujrat states. One out of 45 samples showed variable disintegration and retension factor. The variable disintegration and retention factor which would have been due to substandard quality or other factors including storage. However, HPLC analysis confirms standard active pharmaceutical ingredient, but may be due to humid temperature and moisture in storage may account for the observed result.

Keywords: antimalarial medicines, counterfeit, substandard, TLC

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Authors: Neda Gegar Goshe, M. Moradi, Hossein Rassi

Abstract:

The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The bio transformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose. This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.

Keywords: tylosin, eryK and eryG genes, streptomyces fradiae

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Authors: Nedjar Abdelhadi

Abstract:

The pharmaceutical industry is one of the most important structures and foundations for the management and development of the modern world, especially the advanced part of it, meaning that there are some exceptions for third-world countries. The world today has witnessed radical transformations and changes, some of which made it better and some of which affected the path of its growth. At the beginning of my research, there was a detailed presentation overview of the current situation of the world in terms of growth and development, and it proceeded through that overview as the introduction to my research. The first chapter had divided into three sections; each topic was unique to one of the new methods of manufacturing, deducing and developing medicines Several examples of various recently developed medicines were used The second chapter dealt with the defects and shortcomings that pioneers and drug makers at various levels, as well as various regions and major companies, suffer from on the basis that they are international, especially those specialized in the manufacture of medicines related to viruses and chronic diseases, as well as incurable. As for the third chapter, it was devoted to marketing methods, methods of achieving sales, as well as the basics of spreading medicines and preparing the minds of consumers. Through my research, the one concluded that the current world has become completely different from the world we used to know, and it means by saying the field of manufacturing, selling and marketing medicines. It was noted that one of the biggest factors that affected the change in the field of medicine was the corona disaster. At the end of my research, I was left with nothing but to show the importance and necessity of the pharmaceutical industry and its effective role, not only in the development of mankind, but its main role is in the survival of mankind.

Keywords: health, diseases, medicine, epidemics

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Authors: Sam Bahreini, Payam Hayati

Abstract:

Metal-organic coordination [Cu(L)₄(SCN)₂] was synthesized applying ultrasonic irradiation, and its photocatalytic performance for the degradation of Remdesivir (RS) under sunlight irradiation was systematically explored for the first time in this study. The physicochemical properties of the synthesized photocatalyst were investigated using Fourier-transform infrared (FT-IR), field emission scanning electron microscopy (FE-SEM), powder x-ray diffraction (PXRD), energy-dispersive x-ray (EDX), thermal gravimetric analysis (TGA), diffuse reflectance spectroscopy (DRS) techniques. Systematic examinations were carried out by changing irradiation time, temperature, solution pH value, contact time, RS concentration, and catalyst dosage. The photodegradation kinetic profiles were modeled in pseudo-first order, pseudo-second-order, and intraparticle diffusion models reflected that photodegradation onto [Cu(L)₄(SCN)₂] catalyst follows pseudo-first order kinetic model. The fabricated [Cu(L)₄(SCN)₂] nanostructure bandgap was determined as 2.60 eV utilizing the Kubelka-Munk formula from the diffuse reflectance spectroscopy method. Decreasing chemical oxygen demand (COD) (from 70.5 mgL-1 to 36.4 mgL-1) under optimal conditions well confirmed mineralizing of the RS drug. The values of ΔH° and ΔS° was negative, implying the process of adsorption is spontaneous and more favorable in lower temperatures.

Keywords: Photocatalytic degradation, COVID-19, density functional theory (DFT), molecular electrostatic potential (MEP)

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Authors: Chaiyaporn Yuksen

Abstract:

Backgroud: Supraventricular tachycardia (SVT) is an abnormally fast atrial tachycardia characterized by narrow (≤ 120 ms) and constant QRS. Adenosine was the drug of choice; the first dose was 6 mg. It can be repeated with the second and third doses of 12 mg, with greater than 90% success. The study found that patients observed at 4 hours after normal sinus rhythm was no recurrence within 24 hours. The objective of this study was to investigate the factors that influence the recurrence of SVT after adenosine in the emergency department (ED). Method: The study was conducted retrospectively exploratory model, prognostic study at the Emergency Department (ED) in Faculty of Medicine, Ramathibodi Hospital, a university-affiliated super tertiary care hospital in Bangkok, Thailand. The study was conducted for ten years period between 2010 and 2020. The inclusion criteria were age > 15 years, visiting the ED with SVT, and treating with adenosine. Those patients were recorded with the recurrence SVT in ED. The multivariable logistic regression model developed the predictive model and prediction score for recurrence PSVT. Result: 264 patients met the study criteria. Of those, 24 patients (10%) had recurrence PSVT. Five independent factors were predictive of recurrence PSVT. There was age>65 years, heart rate (after adenosine) > 100 per min, structural heart disease, and dose of adenosine. The clinical risk score to predict recurrence PSVT is developed accuracy 74.41%. The score of >6 had the likelihood ratio of recurrence PSVT by 5.71 times Conclusion: The clinical predictive score of > 6 was associated with recurrence PSVT in ED.

Keywords: clinical prediction score, SVT, recurrence, emergency department

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Authors: Shekoufeh Behdad, Sahar Yadegari, Alireza Ghehrazad, Amirhossein Yadegari

Abstract:

Background: In this study, we compared the effect of intravenous dexamethasone with placebo on hemodynamic variables and hypotension in patients undergoing cesarean section under spinal anesthesia. Materials and methods: This double-blind, randomized clinical trial was conducted with the approval of the university ethics committee. Written informed consent was obtained from all participating patients. Before spinal anesthesia, patients were randomly assigned to receive either dexamethasone (8 mg IV) or placebo (normal saline). Hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate, were measured before drug administration and every 3 minutes until the birth of the neonate and then every 5 minutes until the end of surgery. Side effects such as hypotension, bradycardia, nausea, and vomiting were assessed and recorded for all the patients. Results: There were no significant differences in mean systolic, diastolic, and mean arterial blood pressures before and after administration of the studied drugs in both groups (P.Value>0.05), but heart rate and the incidence of hypotension in the dexamethasone group were less than placebo significantly. Conclusions: Intravenous administration of 8 mg dexamethasone before spinal anesthesia in females undergoing cesarean section can reduce the incidence of post-spinal hypotension without causing serious side effects.

Keywords: cesarean section, hypotension, spinal anesthesia, dexamethasone

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Authors: Chinmayee Choudhury

Abstract:

Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

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Authors: Ezgiamn Abraha Hagos

Abstract:

The primary objective of this study was to assess the existential concerns and related manifestations of higher learning students by investigating their perception of meaningful life and evaluating their purpose in life. In addition, this study was aimed at assessing the manifestations of existential pain among the students. Data was procured using Purpose in Life test (PIL), Well-being Manifestation Measure Scale (WBMMS), and focus group discussion. The total numbers of participants was 478, of which 299 were males and the remaining 179 females. They were selected using a simple random sampling technique. Data was analyzed using two ways. SPSS-version 20 was used to analyze the quantitative part, and narrative modes were utilized to analyze the qualitative data. The research finding revealed that students are involved in risk taking behaviors like alcohol ingestion, drug use, Khat (chat) chewing, and unsafe sex. In line with this it is found out that life in campus was perceived as temporary and as a result the sense of hedonism was prevalent at any cost. Of course, the most important thing for the majority of the students was to know about the purpose of life. Regarding WBMMS, there was no statistically significant difference among males and females and with the exception of the sub-scale of happiness; in all the sub-scales the mean is low. At last, assisting adolescents to develop holistically in terms of body, mind, and spirit is recommended.

Keywords: existential concerns, higher learning institutions, Ethiopia, Aksum University

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Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

Abstract:

Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: Rujnan Tuna, Ulku Baykal

Abstract:

The antineoplastic drugs used in cancer treatment directly have adverse effects on health of both patients receiving the treatment and oncology nurses preparing and administering the treatment. The purpose of this study is to determine the working conditions of the oncology nurses in terms of employee safety as well as their knowledge levels regarding the safe use of antineoplastic drugs. This is a qualitative study conducted in the phenomenological design. Purposeful sampling method was used to carry out the interviews. The individual, in-depth, and semi-structured face-to-face interviews continued with 25 oncology nurses, who were working in an oncology centre in the city of Istanbul. Qualitative content analysis approach was used for the analysis of the obtained data in the study. The results of the study were gathered under 4 main themes; work-related factors, employee safety, working conditions, and training. The interviewed oncology nurses stated that the protective measures related to the safe use of the antineoplastic drugs were insufficient, and only 20% of the nurses have chemotherapy preparation certificate and they received this certificate after they started working in this unit. Also, after they had begun to work in that unit, they started to experience with so many health problems As happens all over the world, there have also been policies and standards regarding the safe use of antineoplastic drugs in Turkey; however, it is found that they remain insufficient to put into practice.

Keywords: antineoplastic drug, employee safety, nurse, oncology, qualitative study

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Authors: Sanaz Seraj, Shohre Rouhani

Abstract:

Recently, graphene has gained much attention because of its unique optical, mechanical, electrical, and thermal properties. Graphene has been used as a key material in the technological applications in various areas such as sensors, drug delivery, super capacitors, transparent conductor, and solar cell. It has a superior quenching efficiency for various fluorophores. Based on these unique properties, the optical sensors with graphene materials as the energy acceptors have demonstrated great success in recent years. During quenching, the emission of a fluorophore is perturbed by a quencher which can be a substrate or biomolecule, and due to this phenomenon, fluorophore-quencher has been used for selective detection of target molecules. Among fluorescence dyes, 1,8-naphthalimide is well known for its typical intramolecular charge transfer (ICT) and photo-induced charge transfer (PET) fluorophore, strong absorption and emission in the visible region, high photo stability, and large Stokes shift. Derivatives of 1,8-naphthalimides have found applications in some areas, especially fluorescence sensors. Herein, the fluorescence quenching of graphene oxide has been carried out on a naphthalimide dye as a fluorescent probe model. The quenching ability of graphene oxide on naphthalimide dye was studied by UV-VIS and fluorescence spectroscopy. This study showed that graphene is an efficient quencher for fluorescent dyes. Therefore, it can be used as a suitable candidate sensing platform. To the best of our knowledge, studies on the quenching and absorption of naphthalimide dyes by graphene oxide are rare.

Keywords: fluorescence, graphene oxide, naphthalimide dye, quenching

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Authors: N. Choobkar, M. Rezaeimanesh, A. M. Emami Rad, M. Ghaeni, H. Norouzi, S. Pahlavani, M. S. Tamasoki, E. Nezafatian

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Antibiotics are used to increase the immune and wound healing in many animals . But due to the residual effects of a drug , researchers sought to replace them with natural materials such as Plant extracts. Falcaria vulgaris is the most attractive sources of the new drugs. Falcaria vulgaris (locally named Ghazzyaghi/Poghazeh) is a member of Umbelliferae family which grows near farmlands and is consumed as a vegetable in some regions of Iran. In the West of the country, in the wound healing and irregularities in the digestive system is also used. There were no scientific reports available in literature in support of the traditional claims of F. vulgaris in fish. The present study is therefore an attempt to assess the efficacy of this indigenous herb for its healing effect in common carp (Cyprinus carpio). Falcaria vulgaris at concentrations of 0, 2 and 10 % with Lophag foods used on wound healing of common carp and immune response, and weight grow and survival during periods of 21 days with feeding 2 times per day on the basis of body weight. The results showed that, compared with the control group, using of concentration 10 % F. vulgaris have significant effect on wound healing and stimulates the immune system by increasing white blood cells (WBC) and weight grow and survival of carp. The herb can used in wound healing, increased resistance to disease and weight grow in fish and the beneficial effects of this combination goes back to man.

Keywords: common carp, falcaria vulgaris, immune response, wound healing

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Authors: Sanjeet Patra, Soham Roychowdhury

Abstract:

In recent times, functionally graded dielectric elastomer (FGDE) has gained significant attention within the realm of soft actuation due to its dual capacity to exert highly localized stresses while maintaining its compliant characteristics on application of electro-mechanical loading. Nevertheless, the full potential of dielectric elastomer (DE) has not been fully explored due to their susceptibility to instabilities when subjected to electro-mechanical loads. As a result, study and analysis of such instabilities becomes crucial for the design and realization of dielectric actuators. Prismatic bifurcation is a type of instability that has been recognized in a DE tube. Though several studies have reported on the analysis for prismatic bifurcation in an isotropic DE tube, there is an insufficiency in studies related to prismatic bifurcation of FGDE tubes. Therefore, this paper aims to determine the onset of prismatic bifurcations on an incompressible FGDE tube when subjected to electrical loading across the thickness of the tube and internal pressurization. The analysis has been conducted by imposing two axial boundary conditions on the tube, specifically axially free ends and axially clamped ends. Additionally, the rigidity modulus of the tube has been linearly graded in the direction of thickness where the inner surface of the tube has a lower stiffness than the outer surface. The static equilibrium equations for deformation of the axisymmetric tube are derived and solved using numerical technique. The condition for prismatic bifurcation of the axisymmetric static equilibrium solutions has been obtained by using the linearized incremental constitutive equations. Two modes of bifurcations, corresponding to two different non-circular cross-sectional geometries, have been explored in this study. The outcomes reveal that the FGDE tubes experiences prismatic bifurcation before the Hessian criterion of failure is satisfied. It is observed that the lower mode of bifurcation can be triggered at a lower critical voltage as compared to the higher mode of bifurcation. Furthermore, the tubes with larger stiffness gradient require higher critical voltages for triggering the bifurcation. Moreover, with the increase in stiffness gradient, a linear variation of the critical voltage is observed with the thickness of the tube. It has been found that on applying internal pressure to a tube with low thickness, the tube becomes less susceptible to bifurcations. A thicker tube with axially free end is found to be more stable than the axially clamped end tube at higher mode of bifurcation.

Keywords: critical voltage, functionally graded dielectric elastomer, linearized incremental approach, modulus of rigidity, prismatic bifurcation

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Authors: Sonia Tamanna, Akramul Hassan, Mohammad Shakil Mahmood, Farzana Ansari, Gowhar Rashid, Mir Fahim Faisal, M. Zakir Hossain Howlader

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Background: Preeclampsia (PE), a pregnancy-specific hypertensive disorder, significantly impacts maternal and fetal health. It is particularly prevalent in underdeveloped countries and is linked to preterm delivery and fetal growth. The renin-angiotensin system (RAS) plays a crucial role in ensuring a successful pregnancy outcome, with Angiotensin-Converting Enzyme 2 (ACE2) being a key component. ACE2 converts ANG II to Ang-(1-7), offering protection against ANG II-induced stress and inflammation while regulating blood pressure and osmotic balance during pregnancy. The reduced maternal plasma angiotensin-converting enzyme 2 (ACE2) seen in preeclampsia might contribute to its pathogenesis. However, there has been a dearth of comprehensive research into the association between ACE2 gene polymorphism and preeclampsia. In the South Asian population, hypertension is strongly linked to two SNPs: rs2285666 and rs879922. This genotype was therefore considered, and the possible association of maternal and fetal ACE2 gene polymorphism with preeclampsia within the Bangladeshi population was evaluated. Method: DNA was extracted from peripheral white blood cells (WBCs) using the organic method, and SNP genotyping was done via PCR-RFLP. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression to determine relative risk. Result: A comprehensive case-control study was conducted on 51 PE patients and their infants, along with 56 control subjects and their infants. Maternal single nuvleotide polymorphisms (SNP) (rs2285666) analysis revealed a strong association between the TT genotype and preeclampsia, with a four-fold increased risk in mothers (P=0.024, OR=4.00, 95% CI=1.36-11.37) compared to their ancestral genotype CC. However, the CT genotype (rs2285666) showed no significant difference (P=0.46, OR=1.54, 95% CI=0.57-4.14). Notably, no significant correlation was found in infants, regardless of their gender. For rs879922, no significant association was observed in both mothers and infants. This pioneering study suggests that mothers carrying the ACE2 gene variant rs2285666 (TT allele) may be at higher risk for preeclampsia, potentially influencing hypertension characteristics, whereas rs879922 does not appear to be associated with developing preeclampsia. Conclusion: This study sheds light on the role of ACE2 gene polymorphism, particularly the rs2285666 TT allele, in maternal susceptibility to preeclampsia. However, rs879922 does not appear to be linked to the risk of PE. This research contributes to our understanding of the genetic underpinnings of preeclampsia, offering insights into potential avenues for prevention and management.

Keywords: ACE2, PCR-RFLP, preeclampsia, single nuvleotide polymorphisms (SNPs)

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Authors: G. A. Oladosu1, P. O. Ogbodogbo, C. I. Makinde1, M. O. Tijani, O. A. Adegboyega

Abstract:

Saprolegniasis is a major pathogenic infection that contributes significantly to poor hatching rates in incubated fish eggs in the Africa catfish hatchery in Nigeria. Malachite green known to be very effective against this condition has been banned because it is carcinogenic. There is, therefore, the need for other effective yet safer methods of controlling saprolegniasis in incubated fish eggs. A total of 50 ml crude, chloroform extract of pyocyanin from which solvent was removed to attain 30 ml, having a concentration of 12.16 ug/ml was produced from 700 ml broth culture of Pseudomonas aeruginosa isolated from a previous study. In-vitro susceptibility of the fungus was investigated by exposing fungal infected eggs to two different time-concentration ratios of pyocyanin; 0.275 ug/ml and 2.75 ug/ml for 1 and 24 hours, and 5 mg/L malachite green as positive control while normal saline was the control. The efficacy of pyocyanin was evaluated using the degree of mycelial growth inhibition in different treatments. Fertilized Clarias gariepinus eggs (between 45 to 64 eggs) were then incubated in 20 ml of medium containing similar concentrations of pyocyanin and malachite green, with freshwater as a control for 24 hours. Hatching rates of the incubated eggs were observed. Three samples of un-hatched eggs were taken from each medium and observed for the presence of fungal pathogens using microscopy. Another batch of three samples of un-hatched eggs from each treatment was also inoculated on Sabourand dextrose agar (SDA) using Egg-Agar Transfer Technique to observe for fungal growth. Mycelial growth was inhibited in fungal infected eggs treated with 2.75 ug/ml for 24 hrs and the 5 mg/L malachite green for both 1 hr and 24 hrs. The mortality rate was 100% in fertilized C. gariepinus eggs exposed for 24 hrs to 0.275 and 2.75 ug/ml of pyocyanin. The mortality rate was least in malachite green followed by the control treatment. Embryonic development was observed to be arrested in the eggs treated with the two pyocyanin concentrations as they maintain their colour but showed no development beyond the gastrula stage, whereas viable eggs in the control and malachite green treatments developed fully into healthy hatchlings. Furthermore, microscopy of the un-hatched eggs revealed the presence of a protozoan ciliate; Colpidium sp, (Tetrahymenidae), as well as a pathogenic fungus; Saprolegnia sp. in the control but not in the malachite green and pyocyanin treatments. Growth of Saprolegnia sp was also observed in SDA culture of un-hatched eggs from the control, but not from pyocyanin and malachite green treated eggs. Pyocyanin treatment of incubated eggs of Clarias gariepinus effectively prevented fungal infection in the eggs, but also arrested the development of the embryo. Therefore, crude chloroform extract of pyocyanin from Pseudomonas aeruginosa cannot be used in the control of Saprolegniasis in incubated Clarias gariepinus eggs at the concentration and duration tested in this study.

Keywords: African catfish, bioprophylaxis, catfish embryo, Saprolegniasis

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Authors: Venkat Garigapati

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Cell-based therapies are limited due to underlying host immune system activity. Microencapsulation of living cells to overcome this issue has some serious drawbacks, such as limitations of nutrient and oxygen diffusion, which pose a threat to the function and longevity of cells. The conformal coating could overcome the issues which are generally involved in traditional microencapsulation. Some of the theoretical advantages of conformal coating include superior nutrient and oxygen supply to cells, prolonged lifespan, improved drug-secreting cell functionality and an opportunity to load high cell doses in small volumes. Despite several advantages to the conformal coating, there are no suitable methods available to apply to living cells. The ultra-thin conformal coating was achieved utilizing click-reactive methacryloyloxyethyl phosphorylcholine (MPC) polymers, which are capable of specifically reacting one polymer to another at neutral pH in the aqueous isotonic system at the desired temperature suitable for living cells without the need of deleterious initiators. ARPE-19 (Adult Retinal Pigment Epithelial cell line-19) cell-spheroids and rat pancreatic islets were used in the formulation studies. The in vitro studies of coated ARPE-19 cell-spheroids and rat islets indicate that the coat was intact; cells were viable and functioning. The in vitro study results revealed that the conformal coating technology seems promising and in vivo studies are being planned.

Keywords: cells, hydrogel, conformal coating, microencapsulation, insulin

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Authors: Shital Suresh Borse, Vijayalaxmi Kadroli

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E-commerce industries nowadays implement the latest AI, ML Techniques to improve their own performance and prediction accuracy. This helps to gain a huge profit from the online market. Ant Colony Optimization, Genetic algorithm, Particle Swarm Optimization, Neural Network & GWO help many e-commerce industries for up-gradation of their predictive performance. These algorithms are providing optimum results in various applications, such as stock price prediction, prediction of drug-target interaction & user ratings of similar products in e-commerce sites, etc. In this study, customer reviews will play an important role in prediction analysis. People showing much interest in buying a lot of services& products suggested by other customers. This ultimately increases net profit. In this work, a convolution neural network (CNN) is proposed which further is useful to optimize the prediction accuracy of an e-commerce website. This method shows that CNN is used to optimize hyperparameters of GWO algorithm using an appropriate coding scheme. Accurate model results are verified by comparing them to PSO results whose hyperparameters have been optimized by CNN in Amazon's customer review dataset. Here, experimental outcome proves that this proposed system using the GWO algorithm achieves superior execution in terms of accuracy, precision, recovery, etc. in prediction analysis compared to the existing systems.

Keywords: prediction analysis, e-commerce, machine learning, grey wolf optimization, particle swarm optimization, CNN

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Authors: Nishal Parbhoo, John B. Dewar, Samantha Gildenhuys

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Rotavirus is the major cause of severe gastroenteritis worldwide in children aged 5 and younger. Death rates are high particularly in developing countries. The mature rotavirus is a non-enveloped triple-layered nucleocapsid containing 11 double-stranded RNA segments. Here a global view on the sequence and structure of the three main capsid proteins, VP7, VP6, and VP2 is taken by generating a consensus sequence for each of these rotavirus proteins, for each species obtained from published data of representative rotavirus genotypes from across the world and across species. The degree of conservation between species was represented on homology models for each of the proteins. VP7 shows the highest level of variation with 14 - 45 amino acids showing conservation of less than 60%. These changes are localized to the outer surface which is exposed to antibodies alluding to a possible mechanism in evading the immune system. The middle layer, VP6 shows lower variability with only 14-32 sites having lower than 70% conservation. The inner structural layer made up of VP2 showed the lowest variability with only 1-16 sites having less than 70% conservation across species. The results correlate with proteins’ multiple structural roles. Although the nucleotide sequences vary due to an error-prone replication and lack of proofreading, the corresponding amino acid sequence of VP2, 6 and 7 remains conserved. Sequence conservation maintained for the virus results in stable protein structures, fit for function. This can be exploited in drug design, molecular studies and biotechnological applications.

Keywords: amino acid sequence conservation, capsid protein, protein structure, vaccine candidate

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Authors: Sandhyarani Guggilla

Abstract:

For several reasons no two individuals can be considered identical and hence individualization of therapy is the current trend in treating the patients. Influence of menstrual cycle on the pharmacokinetics of Doxycycline. Twelve healthy female volunteers have been included in the study after obtaining written informed consent. The age ranged from 16 to 25 years. Experimental design: The volunteer selection and recruitment will be carried out after obtaining informed consent from each volunteer. The drug administration will be done to each volunteer at 7 a.m along with a glass of water after an overnight fasting on 3rd, 13th and 23rd day of menstrual cycle. These saliva samples will be stored under frozen conditions until HPLC analysis. Results: In the present study the changes in estrogen levels during ovulatory phase have not shown any influence onAUCo-t of Doxycycline. Only AUCo-t of doxycycline showed an increasing trend with increasing levels of estrogen in ovulatory phase, but not in other phases. Even though the FSH levels differed significantly among volunteers during different phases FSH does not seem to influence the overall pharmacokinetic behavior of Doxycycline during different phases. The present study indicated only the trend that the hormone levels may influence the pharmacokinetic behavior of the Doxycycline. Conclusion: In the present study the changes in hormones have shown an increasing C-max, increasing AUCo-t of Doxycycline pharmacokinetics significantly in follicular phase than ovulatory and luteal phases among volunteers during different phases. In other pharmacokinetic properties like clearance, biological half-life, volume of distribution, mean residence time the change was not significant.

Keywords: menstrual cycle, doxycycline, estrogen, FSH, ovulatory phase

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Authors: Shubham Dwivedi, Raghavender Medishetti, Rita Rani, Aarti Sevilimedu, Pushkar Kulkarni, Yogeeswari Perumal

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder of early onset, characterized by impaired sociability, cognitive function and stereotypies. There is a significant urge to develop and establish new animal models with ASD-like characteristics for better understanding of underlying mechanisms. The aim of the present study was to develop a cost and time effective zebrafish model with quantifiable parameters to facilitate mechanistic studies as well as high-throughput screening of new molecules for autism. Zebrafish embryos were treated with valproic acid and a battery of behavioral tests (anxiety, inattentive behavior, irritability and social impairment) was performed on larvae at 7th day post fertilization, followed by study of molecular markers of autism. This model shows a significant behavioural impairment in valproic acid treated larvae in comparison to control which was again supported by alteration in few marker genes and proteins of autism. The model also shows a rescue of behavioural despair with positive control drugs. The model shows robust parameters to study behavior, molecular mechanism and drug screening approach in a single frame. Thus we postulate that our 7 days zebrafish larval model for autism can help in high throughput screening of new molecules on autism.

Keywords: autism, zebrafish, valproic acid, neurodevelopment, behavioral assay

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Authors: B. Medani Amna, M. A. Elbadwi Samia, E. Amin Ahmed

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Variable plants present in nature are used by simple rural and urban people, researchers and drug manufacturers for medicinal purposes. Garad is one of the most commonly used in Sudan for both treatment and prophylaxis of infections in the respiratory, urinogenital tracts and the skin. Water exctracts from Acacia nilotica bods were used in this very experiment to test for their toxicity to Nubian goats at two dose rates under proper experimental conditions. The clinical, pathological, haematological and biological changes in Nubian goats given daily oral doses of 1 and 5 g/kg body weight of Acacia nilotica to two groups of test goats. The goats of the control group were undosed with Acacia nilotica.Other than the dose co-related mortality rates, the clinical signs were observed to be salivation, staggered gait, intermittent loss of voice and low appetite. On histopathological testing, the main lesions were hepatic centrolobular necrosis and fatty changes associated with the significant changes in GGT and ALP are indicating hepatic dysfunction.Renal malfunction is indicated by haemorrhages in addition to the change in the urea concentration. The congested, haemorrhagic, emphysematous, edematous and cyanotic lungs may contribute to the development of dyspnea. Acacia nilotica poisoning may lead to an immunosuppression pointed out by the lymphocyte infiltration. On evaluation of the above results, Acacia nilotica was considered toxic to Nubian goats at the above mentioned doses. Future work for Acacia nilotica was forwarded and practical implications of the result were highlighted.

Keywords: Acaia nilotica, toxicity data, Nubian goats, Garad

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Authors: G. Fitzpatrick, S. O. Chonghaile, D. Harmon

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Objective: Chronic pain patients represent a unique challenge in the Emergency Department. Very little literature has been published regarding this group of patients. Our aim was to determine the attitude of patients with chronic pain to the Emergency Department in order to improve and streamline their future visits. Methods: A two-year survey was carried out on Chronic Pain Patients regarding their Emergency Department Attendances. Patients attending the Pain Clinic in Croom Hospital, Co. Limerick were asked to complete a 20-part questionnaire regarding their experiences of visiting the Emergency Department in the preceding year. 46 questionnaires were completed. Results: Unbearable breakthrough pain was the main reason for visiting the Emergency Department. More than half (54%) of those surveyed were not satisfied with the treatment received. Problems indicated included under-treatment of pain (59%), a sense of being under undue suspicion of drug-seeking behaviour (33%) and a perception that the patient themselves understood their condition better than the treating doctor (76%). Paracetamol, NSAIDs, or time off work comprised 72% of the treatments offered – all of which could have been provided by their General Practitioner. Only 4% were offered a nerve block. 67% felt that the creation of personalised Patient Plans, consisting of an agreed plan between the patient, their pain specialist, and the Emergency Department, would expedite their trip through the Emergency Department. Conclusions: Chronic pain patients generally have a negative experience in the ED. Possible future solutions include increasing our empathy and levels of knowledge, provision of nerve blocks in the ED, and use of personalised “Patient Plans” to streamline the treatment pathway for this group of patients.

Keywords: chronic pain, survey, patients, emergency department

Procedia PDF Downloads 372