Search results for: therapeutic agents
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2842

Search results for: therapeutic agents

832 A Review of Benefit-Risk Assessment over the Product Lifecycle

Authors: M. Miljkovic, A. Urakpo, M. Simic-Koumoutsaris

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Benefit-risk assessment (BRA) is a valuable tool that takes place in multiple stages during a medicine's lifecycle, and this assessment can be conducted in a variety of ways. The aim was to summarize current BRA methods used during approval decisions and in post-approval settings and to see possible future directions. Relevant reviews, recommendations, and guidelines published in medical literature and through regulatory agencies over the past five years have been examined. BRA implies the review of two dimensions: the dimension of benefits (determined mainly by the therapeutic efficacy) and the dimension of risks (comprises the safety profile of a drug). Regulators, industry, and academia have developed various approaches, ranging from descriptive textual (qualitative) to decision-analytic (quantitative) models, to facilitate the BRA of medicines during the product lifecycle (from Phase I trials, to authorization procedure, post-marketing surveillance and health technology assessment for inclusion in public formularies). These approaches can be classified into the following categories: stepwise structured approaches (frameworks); measures for benefits and risks that are usually endpoint specific (metrics), simulation techniques and meta-analysis (estimation techniques), and utility survey techniques to elicit stakeholders’ preferences (utilities). All these approaches share the following two common goals: to assist this analysis and to improve the communication of decisions, but each is subject to its own specific strengths and limitations. Before using any method, its utility, complexity, the extent to which it is established, and the ease of results interpretation should be considered. Despite widespread and long-time use, BRA is subject to debate, suffers from a number of limitations, and currently is still under development. The use of formal, systematic structured approaches to BRA for regulatory decision-making and quantitative methods to support BRA during the product lifecycle is a standard practice in medicine that is subject to continuous improvement and modernization, not only in methodology but also in cooperation between organizations.

Keywords: benefit-risk assessment, benefit-risk profile, product lifecycle, quantitative methods, structured approaches

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831 Human Par14 and Par17 Isomerases Bind Hepatitis B Virus Components Inside and Out

Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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830 Differential Diagnosis of Malaria and Dengue Fever on the Basis of Clinical Findings and Laboratory Investigations

Authors: Aman Ullah Khan, Muhammad Younus, Aqil Ijaz, Muti-Ur-Rehman Khan, Sayyed Aun Muhammad, Asif Idrees, Sanan Raza, Amar Nasir

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Dengue fever and malaria are important vector-borne diseases of public health significance affecting millions of people around the globe. Dengue fever is caused by Dengue virus while malaria is caused by plasmodium protozoan. Generally, the consequences of Malaria are less severe compared to dengue fever. This study was designed to differentiate dengue fever and malaria on the basis of clinical and laboratory findings and to compare the changes in both diseases having different causative agents transmitted by the common vector. A total of 200 patients of dengue viral infection (120 males, 80 females) were included in this prospective descriptive study. The blood samples of the individuals were first screened for malaria by blood smear examination and then the negative samples were tested by anti-dengue IgM strip. The strip positive cases were further screened by IgM capture ELISA and their complete blood count including hemoglobin estimation (Hb), total and differential leukocyte counts (TLC and DLC), erythrocyte sedimentation rate (ESR) and platelet counts were performed. On the basis of the severity of signs and symptoms, dengue virus infected patients were subdivided into dengue fever (DF) and dengue hemorrhagic fever (DHF) comprising 70 and 100 confirmed patients, respectively. On the other hand, 30 patients were found infected with Malaria while overall 120 patients showed thrombocytopenia. The patients of DHF were found to have more leucopenia, raised hemoglobin level and thrombocytopenia < 50,000/µl compared to the patients belonging to DF and malaria. On the basis of the outcomes of the study, it was concluded that patients affected by DF were at a lower risk of undergoing haematological disturbance than suffering from DHF. While, the patients infected by Malaria were found to have no significant change in their blood components.

Keywords: dengue fever, blood, serum, malaria, ELISA

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829 Animal-Assisted Therapy: A Perspective From Singapore

Authors: Julia Wong, Hua Beng Lim, Petrina Goh, Johanna Foo, Caleb Ng, Nurul ‘Aqilah Bte Mohd Taufek

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Animal-assisted therapy (AAT) utilizes human-animal interaction to achieve specific therapeutic goals, and its efficacy has been demonstrated across various settings overseas. The use of AAT in Singapore, however, is still limited. Ang Mo Kio-Thye Hua Kwan (AMKH) is one of the first community hospitals in Singapore to use AAT to complement its occupational therapy services with elderly patients. This study explored the perspectives of AMKH’s occupational therapists (OTs) in relation to AAT to understand barriers and enablers in implementing and practising AAT. We also examined how OTs at-large across practice settings perceive AAT. A mixed method design was used. 64 OTs at-large participated in on online survey, and 7 AMKH OTs were interviewed individually via Zoom. Survey results were analysed with descriptive and Mann-Whitney U tests. Interviews were thematically analysed. AMKH OTs perceived various benefits of AAT articulated in overseas studies in domains such as motivation and participation, emotional, social interaction, sensory tactile stimulation, and cognition. Interestingly, this perception was also supported by 67% of OTs who had responded to the survey, even though most of the OTs who had participated in the survey had no experience in AAT. Despite the perceived benefits of AAT, both OTs from AMKH and those at-large articulated concerns on risks pertaining to AAT (e.g., allergies, unexpected animal behaviour, infections, etc). However, AMKH OTs shared several ways to mitigate these risks, demonstrating their ability to develop a safe program. For e.g., volunteers and their dogs must meet specific recruitment criteria, stringent protocols are used to screen and match dogs with patients, and there are strict exclusion criteria for patients participating in AAT. AMKH OTs’ experience suggests that additional skills and knowledge are required to implement AAT, therefore, healthcare institutions should first consider improving their staff training and risk mitigation knowledge before implementing AAT. They can also refer to AMKH’s AAT protocols and those found in overseas studies, but institutions must adapt the protocols to fit their institutional settings and patients’ profiles.

Keywords: animal-assisted therapy, dog-assisted therapy, occupational therapy, complementary therapy

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828 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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827 In Exile but Not at Peace: An Ethnography among Rwandan Army Deserters in South Africa

Authors: Florence Ncube

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This paper examines the military and post-military experiences of soldiers who deserted from the Rwanda Defence Force (RDF) and tried to make a living in South Africa. Because they are deserters, they try to hide their military identity, yet it is simultaneously somewhat coercively ascribed to them by the Rwandan state and can put them in potential danger. The paper attends to the constructions, experiences, practices, and subjective understanding of the deserters’ being in exile to examine how, under circumstances of perceived threat, these men navigate real or perceived state-sponsored surveillance and threat in non-military settings in South Africa where they have become potential political and disciplinary targets. To make sense of the deserters’ experiences in these circumstances, the paper stitches together a number of useful theoretical concepts, including Bourdieu’s (1992) theory of practice and Vigh’s (2009; 2018) concept of social navigation because no single approach can coherently analyze the specificity of this study. Conventional post-military literature privileges an understanding of army desertion as a malignancy and somewhat problematic. Little is known about the military and post-military experiences of deserters who believe that army desertion is in fact a building block towards achieving subjective peace, even in the context of exile. The paper argues that the presence of Rwandan state agents in South Africa strips the context of the exile of its capacity to provide the deserters with peace, safety, and security. This paper recenters army desertion in analyses of militarism, soldiering, and transition in African contexts and complicates commonsense understandings of army desertion which assume that it is entirely problematic. This paper is drawn from an ethnography conducted among 30 junior-rank Rwandan army deserters exiled in Johannesburg and Cape Town. The researcher employed life histories, in-depth interviews, and deep hangouts to collect data.

Keywords: army deserter, military, identity, exile, peacebuilding, South Africa

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826 Study of the Biochemical Properties of the Protease Coagulant Milk Extracted from Sunflower Cake: Manufacturing Test of Cheeses Uncooked Dough Press and Analysis of Sensory Properties

Authors: Kahlouche Amal, Touzene F. Zohra, Betatache Fatihaet Nouani Abdelouahab

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The development of the world production of the cheese these last decades, as well as agents' greater request cheap coagulants, accentuated the search for new surrogates of the rennet. What about the interest to explore the vegetable biodiversity, the source well cheap of many naturals metabolites that the scientists today praise it (thistle, latex of fig tree, Cardoon, seeds of melon). Indeed, a big interest is concerned the search for surrogates of vegetable origin. The objective of the study is to show the possibility of extracting a protease coagulant the milk from the cake of Sunflower, available raw material and the potential source of surrogates of rennet. so, the determination of the proteolytic activity of raw extracts, the purification, the elimination of the pigments of tint of the enzymatic preparations, a better knowledge of the coagulative properties through study of the effect of certain factors (temperature, pH, concentration in CaCl2) are so many factors which contribute to value milk particularly those produced by the small ruminants of the Algerian dairy exploitations. Otherwise, extracts coagulants of vegetable origin allowed today to value traditional, in addition, although the extract coagulants of vegetable origin made it possible today to develop traditional cheeses whose Iberian peninsula is the promoter, but the test of 'pressed paste not cooked' cheese manufacturing led to the semi-scale pilot; and that, by using the enzymatic extract of sunflower (Helianthus annus) which gave satisfactory results as well to the level of outputs as on the sensory level,which, statistically,did not give any significant difference between studied cheeses. These results confirm the possibility of use of this coagulase as a substitute of rennet commercial on an industrial scale.

Keywords: characterization, cheese, Rennet, sunflower

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825 Cationic Copolymer-Functionalized Nanodiamonds Stabilizes Silver Nanoparticles with Dual Antibacterial Activity and Lower Cytotoxicity

Authors: Weiwei Cao, Xiaodong Xing

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In order to effectively resolve the microbial pollution and contamination, synthetic nano-antibacterial materials are widely used in daily life. Among them, nanodiamonds (NDs) have recently been demonstrated to hold promise as useful materials in biomedical applications due to their high specific surface area and biocompatibility. In this work, the copolymer, poly(4-vinylpyridine-co-2-hydroxyethyl methacrylate) was applied for the surface functionalization of NDs to produce the quaternized poly(4-vinylpyridine-co-2-hydroxyethyl methacrylate)-functionalized NDs (QNDs). Then, QNDs were used as a substrate for silver nanoparticles (AgNPs) to produce a QND@Ag hybrid. The composition and morphology of the resultant nanostructures were confirmed by Fourier transform infrared spectra (FT-IR), transmission electron microscope (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The mass fraction of AgNPs in the nanocomposites was about 35.7%. The antibacterial performances of the prepared nanocomposites were evaluated with Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus by minimum inhibitory concentration (MIC), inhibition zone testing and time-kill study. As a result, due to the synergistic antibacterial activity of QND and AgNPs, this hybrid showed substantially higher antibacterial activity than QND and polyvinyl pyrrolidone (PVP)-stabilized AgNPs, and the AgNPs on QND@Ag were more stable than the Ag NPs on PVP, resulting in long-term antibacterial effects. More importantly, this hybrid showed excellent water solubility and low cytotoxicity, suggesting the great potential application in biomedical applications. The present work provided a simple strategy that successfully turned NDs into nanosized antibiotics with simultaneous superior stability and biocompatibility, which would broaden the applications of NDs and advance the development of novel antibacterial agents.

Keywords: cationic copolymer, nanodiamonds, silver nanoparticles, dual antibacterial activity, lower cytotoxicity

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824 Malaysian Knowledge, Belief and Attitude towards Hypnosis as a Health Intervention: An Interpretative Phenomenological Analysis

Authors: Ying Chern Yeoh, Mark J. Forshaw

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Although hypnosis has been widely endorsed in Europe since 1950s, it was still viewed as a typically new therapy in Asia. There are very little findings regarding hypnosis in Asian countries, especially in culturally diverse countries such as Malaysia. The knowledge of the beneficial effects of hypnosis was not widespread to the public, however knowledge of the negative effects was frequently being highlighted. Therefore, the acceptance of hypnosis as a new effective health treatment can be a challenge in Malaysia. Recognising Malaysian’s perception, belief and attitude towards hypnosis could increase the public awareness of hypnosis, which in turn will alter their misconception and increase acceptance of hypnosis as an effective therapy. Eight individuals (N = 8) from the general public with different background, ethnicity (Malays, Chinese and Indians) and religion (Islamic, Buddhism, Hinduism, Taoism, Christianity, free-thinker) and two local experienced practitioners with minimum of five years experiences (N = 2) were being interviewed to determine their views, beliefs and level of acceptance towards hypnosis. Semi-structured interviews were conducted, transcribed with pseudonyms and analyzed by using Interpretative Phenomenological Analysis. The three emergent themes were illustrated under the captions of ‘traditional vs mainstream’, ‘myths vs truth’, and ‘dissemination and public awareness’. The finding suggested that individual knowledge and personal experience primarily influenced people’s level of acceptance towards hypnosis as a beneficial health treatment, rather than the diversity of cultural and religious background. Subsequent findings regarding hypnosis and the effort of promoting it will provide the society an opportunity to increase public education and health awareness. Several associations had started to advance its development by organizing conferences and setting up therapeutic centers. However, health promotion on hypnosis is yet to be conducted to raise public awareness of its beneficial effects. By requesting for hypnosis to be included as a subject in medical education and psychology curriculum and formatting it under Ministry of Health’s legislation body might enhance the knowledge of hypnosis for Malaysian as one of the health intervention in the future.

Keywords: awareness, hypnosis, intervention, Malaysian, promotion

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823 Investigating the Potential Use of Unsaturated Fatty Acids as Antifungal Crop Protective Agents

Authors: Azadeh Yasari, Michael Ganzle, Stephen Strelkov, Nuanyi Liang, Jonathan Curtis, Nat N. V. Kav

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Pathogenic fungi cause significant yield losses and quality reductions to major crops including wheat, canola, and barley. Toxic metabolites produced by phytopathogenic fungi also pose significant risks to animal and human health. Extensive application of synthetic fungicides is not a sustainable solution since it poses risks to human, animal and environmental health. Unsaturated fatty acids may provide an environmentally friendly alternative because of their direct antifungal activity against phytopathogens as well as through the stimulation of plant defense pathways. The present study assessed the in vitro and in vivo efficacy of two hydroxy fatty acids, coriolic acid and ricinoleic acid, against the phytopathogens Fusarium graminearum, Pyrenophora tritici-repentis, Pyrenophora teres f. teres, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Antifungal activity of coriolic acid and ricinoleic acid was evaluated using broth micro-dilution method to determine the minimum inhibitory concentration (MIC). Results indicated that both ricinoleic acid and coriolic acid showed antifungal activity against phytopathogens, with the strongest inhibitory activity against L. maculans, but the MIC varied greatly between species. An antifungal effect was observed for coriolic acid in vivo against pathogenic fungi of wheat and barley. This effect was not correlated to the in vitro activity because ricinoleic acid with equivalent in vitro antifungal activity showed no protective effect in vivo. Moreover, neither coriolic acid nor ricinoleic acid controlled fungal pathogens of canola. In conclusion, coriolic acid inhibits some phytopathogens in vivo and may have the potential to be an effective crop protection agent.

Keywords: coriolic acid, minimum inhibitory concentration, pathogenic fungi, ricinoleic acid

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822 Green Synthesis and Characterization of Zinc Oxide Nanoparticles Using Neem (Azadirachta Indica) Leaf Extract and Investigation of Its Antibacterial Activities

Authors: Emineh Tsegahun Gedif

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Zinc oxide nanoparticles (ZnO NPs) have garnered significant attention due to their diverse applications encompassing catalytic, optical, photonic, and antibacterial properties. In this study, we successfully synthesized zinc oxide nanoparticles using a rapid, environmentally benign, and cost-effective method. Neem (Azadirachta indica) leaf extract served as the reducing agent for Zn (NO₃)₂.6H2O solution under optimized conditions (pH = 9). Qualitative screening techniques and FT-IR Spectroscopy confirmed the presence of active biomolecules such as flavonoids, phenolic groups, alkaloids, terpenoids, and tannins within the Neem leaf extract, both before and after reduction. The formation of ZnO NPs was visually evident through a distinct color change from colorless to light yellow. The biosynthesized nanoparticles underwent comprehensive characterization through UV-visible, FT-IR, and XRD spectroscopies. The reduction process proved to be straightforward and user-friendly, with UV-visible spectroscopy demonstrating a surface plasmon resonance (SPR) at 321 nm, unequivocally confirming the ZnO NP formation. X-ray diffraction analysis elucidated the crystal structure, revealing an average particle size of approximately 20 nm using Scherrer's equation based on the line width of the plane. Furthermore, the synthesized zinc oxide nanoparticles were evaluated for their antimicrobial properties against both Gram-positive and Gram-negative bacteria. The results showcased significant inhibitory activity, with the highest zone of inhibition observed against Escherichia coli (15 mm) and comparatively lower activity against Staphylococcus aureus. This research underscores the potential of Neem leaf extract-mediated synthesis of ZnO NPs as an eco-friendly and effective approach for various applications, including antibacterial agents.

Keywords: zinc oxide nanoparticles (ZnO NPs), bioreducing agent, green synthesis, antibacterial activity

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821 Physicochemical and Functional significance of Two Lychee (Litchi chinensis Sonn.) Cultivars Gola and Surakhi from Pakistan

Authors: Naila Safdar, Faria Riasat, Azra Yasmin

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Lychee is an emerging fruit crop in Pakistan. Two famous cultivars of lychee, Gola and Surakhi, were collected from Khanpur Orchard, Pakistan and their whole fruit (including peel, pulp and seed) was investigated for pomological features and therapeutic activities. Both cultivars differ in shape and size with Gola having large size (3.27cm length, 2.36cm width) and more flesh to seed ratio (8.65g). FTIR spectroscopy and phytochemical tests confirmed presence of different bioactive compounds like phenol, flavonoids, quinones, anthraquinones, tannins, glycosides, and alkaloids, in both lychee fruits. Atomic absorption spectroscopy indicated an increased amount of potassium, magnesium, sodium, iron, and calcium in Gola and Surakhi fruits. Small amount of trace metals, zinc and copper, were also detected in lychee fruit, while heavy metals lead, mercury, and nickel were absent. These two lychee cultivars were also screened for antitumor activity by Potato disc assay with maximum antitumor activity shown by aqueous extract of Surakhi seed (77%) followed by aqueous extract of Gola pulp (74%). Antimicrobial activity of fruit parts was checked by agar well diffusion method against six bacterial strains Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Bacillus subtilis, Bacillus sp. MB083, and Bacillus sp. MB141. Highest antimicrobial activity was shown by methanolic extract of Gola pulp (27mm ± 0.70) and seed (19.5mm ± 0.712) against Enterococcus faecalis. DPPH scavenging assay revealed highest antioxidant activity by aqueous extract of Gola peel (98.10%) followed by n-hexane extract of Surakhi peel (97.73%). Results obtained by reducing power assay also corroborated with the results of DPPH scavenging activity.

Keywords: antimicrobial evaluation, antitumor assay, gola, phytoconstituents, reactive oxygen species, Surakhi

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820 Inhibition of Echis ocellatus Venom Metalloprotease by Flavonoid-Rich Ethyl Acetate Sub-fraction of Moringa oleifera Leaves (Lam.): in vitro and in silico Approaches

Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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819 Protective Effects of Coenzyme Q10 and N-Acetylcysteine on Myocardial Oxidative Stress, Inflammation, and Impaired Energy metabolism in Carbon Tetrachloride Intoxicated Rats

Authors: Nayira A. Abd Elbaky, Amal J. Fatani, Hazar Yaqub, Nouf M. Al-Rasheed, Naglaa El-Orabi, Mai Osman

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The present work is aimed to evaluate the protective effect of N-acetyl cystiene (NAC), coenzyme Q10 (CoQ10), and their combination against carbon tetrachloride (CCl4)-induced cardiotoxicity in rats. CCl4 treatment significantly elevated the levels of cardiac oxidative stress bio markers including nitric oxide (NO) and malondialdehyde (MDA). A concomitant decrease in the level of reduced glutathione and the activity of membrane bound enzyme, calcium-adenosine triphosphatase were observed in the hearts of rats exposed to CCl4 compared to respective values in normal group. Quantitative analysis of myocardial energy metabolism revealed a significant decrease in the glucose content coupled with depletion in the activities of myocardial glycolytic enzymes as hexokinase (HK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) after CCl4 treatment. In addition, a significant elevation in myocardial hydroxyproline level was observed in CCl4 intoxicated rats indicating interstitial collagen accumulation. Pretreatment with either NAC, CoQ10 or their combination successively alleviated the alterations in myocardial oxidative stress and antioxidant markers, as well as effectively up-regulated the decrease in cardiac energetic biomarkers in CCl4 intoxicated rats. Moreover, these antioxidants markedly reduced myocardial hydroxyproline level versus that of CCl4-treated animals. In conclusion, the present results illustrated that the prophylactic use of the current antioxidant resulted in a remarkable cardioprotective effect against CCl4 induced myocardial damage, which suggest that they may candidates as prophylactic agents against different cardio-toxins.

Keywords: carbon tetrachloride, lipid peroxidation, antioxidant, energy metabolism, hydroxyproline

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818 Effect of Agricultural Extension Services on Technical Efficiency of Smallholder Cassava Farmers in Ghana: A Stochastic Meta-Frontier Analysis

Authors: Arnold Missiame

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In Ghana, rural dwellers who depend primarily on agriculture for their livelihood constitute about 60% of the country’s population. This shows the critical role and potentials of the agricultural sector in helping to achieve Ghana’s vision 2030. With the current threat of climate change and advancements in technology, agricultural extension is not just about technology transfer and improvements in productivity, but it is also about improving the managerial and technical skills of farmers. In Ghana, the government of Ghana as well as other players in the sector like; non-governmental organizations, NGOs, local and international funding agencies, for decades now, have made capacity-building-investments in smallholder farmers by way of extension services delivery. This study sought to compare the technical efficiency of farmers who have access to agricultural extension and farmers who do not in Ghana. The study employed the stochastic meta-frontier model to analyze household survey data comprising 300 smallholder cassava farmers from the Fanteakwa district of Ghana. The farmers were selected through a two-stage sampling technique where 5 communities were purposively selected in the first stage and then 60 smallholder cassava farmers were randomly selected from each of the 5 communities. Semi-structured questionnaires were used to collect data on farmers’ socioeconomic and farm-level characteristics. The results showed that farmers who have access to agricultural extensions services have higher technical efficiencies (TE) and produce much closer to their meta-production frontiers (higher technology gap ratios (TGR) than farmers who do not have access to such extension services. Furthermore, experience in cassava cultivation and formal education significantly improves the technical efficiencies of farmers. The study recommends that the mode and scope of agricultural extension service delivery in the country should be enhanced to ensure that smallholder farmers have easy access to extension agents.

Keywords: agricultural extension, Ghana, smallholder farmers, stochastic meta-frontier model, technical efficiency

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817 Bioavailability Enhancement of Ficus religiosa Extract by Solid Lipid Nanoparticles

Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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816 Ethical Discussions on Prenatal Diagnosis: Iranian Case of Thalassemia Prevention Program

Authors: Sachiko Hosoya

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Objectives: The purpose of this paper is to investigate the social policy of preventive genetic medicine in Iran, by following the legalization process of abortion law and the factors affecting the process in wider Iranian contexts. In this paper, ethical discussions of prenatal diagnosis and selective abortion in Iran will be presented, by exploring Iranian social policy to control genetic diseases, especially a genetic hemoglobin disorder called Thalassemia. The ethical dilemmas in application of genetic medicine into social policy will be focused. Method: In order to examine the role of the policy for prevention of genetic diseases and selective abortion in Iran, various resources have been sutudied, not only academic articles, but also discussion in the Parliament and documents related to a court case, as well as ethnographic data on living situation of Thalassemia patients. Results: Firstly, the discussion on prenatal diagnosis and selective abortion is overviewed from the viewpoints of ethics, disability rights activists, and public policy for lower-resources countries. As a result, it should be noted that the point more important in the discussion on prenatal diagnosis and selective abortion in Iran is the allocation of medical resources. Secondly, the process of implementation of national thalassemia screening program and legalization of ‘Therapeutic Abortion Law’ is analyzed, through scrutinizing documents such as the Majlis record, government documents and related laws and regulations. Although some western academics accuse that Iranian policy of selective abortion seems to be akin to eugenic public policy, Iranian government carefully avoid to distortions of the policy as ‘eugenic’. Thirdly, as a comparative example, discussions on an Iranian court case of patient’s ‘right not to be born’ will be introduced. Along with that, restrictive living environments of people with Thalassemia patients and the carriers are depicted, to understand some disabling social factors for people with genetic diseases in the local contexts of Iran.

Keywords: abortion, Iran, prenatal diagnosis, public health ethics, Thalassemia prevention program

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815 DSC2 Promotes the Proliferation, Metastasis and Drug Resistance of Lung Cancer by Activating the PI3K/AKT Pathway

Authors: Qi LI, Xu Lin, Nengming Lin

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Objective: The aim of this study was to investigate the role of desmocollin 2 (DSC2) protein in the proliferation, migration and drug resistance of lung cancer cells. Method: CCK-8 assays and colony formation assays were used to evaluate the effect of dsc2 regulation on cancer cell viability and colony formation. Transwell assays and wound healing assays were also performed. Cell flow double staining was used to detect the apoptosis rate of cells with DSC2, which was added cisplatin. Western blot assay was used to detect cell cycle, PI3k/Akt and apoptosis-related proteins. Results: Our data showed that dsc2 is upregulated in clinical lung cancer tissues compared with pericarcinomatous tissues, and it is differentially expressed in lung cancer cell lines. The down-regulation of dsc2 in A549 and H358 lung cancer cells significantly suppressed the cell proliferation, metastasis, and motility. In contrast, the opposite effects were observed in overexpression of dsc2 both in H23 and PC9 cell lines. In addition to lung adenocarcinoma cell lines, we also examined its expression in lung squamous cell lines, such as H226. Western blotting showed that dsc2 could reduce the level of phosphorylated Akt (Ser 473) and p-mTOR. Thus, it is speculated that dsc2 up-regulation promotes proliferation and invasiveness through activation of the PI3K/AKT pathway. Also, knockdown of dsc2 in A549 and H226 could significantly decreased in the levels of cyclinB and wee1 protein. Additionally, flow cytometry showed that dsc2 knockdown combined with cisplatin could significantly enhance cell apoptosis rate. Conclusion: These data suggest that dsc2 promotes the proliferation and migration of lung cancer cells in vitro. Also, the results suggested that dsc2 could affect the cell cycle and apoptosis of lung cells. Furthermore, knockdown of dsc2 could sensitize cisplatin in both lung adenocarcinoma and lung squamous cell lines. Thus we suggested that dsc2 can be used as a therapeutic target for lung cancer.

Keywords: desmocollin 2, cisplatin, lung cancer, PI3K/AKT, lung squamous cell

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814 Adoption of Risk and Insurance among Aquaculture Producers in Khuzestan Province, Iran

Authors: Kiyanoush Ghalavand

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Aquaculture production is inherently a risky business, and farmers face a variety of weather, pest, disease, inptut supply, and market related risks. There are many factors out farmers control and unpredictable. Insurance has an important role in aquaculture production and is a tool to support farmers against threats. Investigation of factors affecting aquaculture farmers' adoption of aquaculture insurance strategy was the objective of this study. The purpose of this study was determining the related factors to adoption of insurance by aquaculture farmers in Khuzestan province, Iran. The research design was a descriptive and correlation surveying method. Aquaculture farmers in Khuzestan province were the target population for this study. A random sample of aquaculture selected (N=1830, n =139). The main result of the study reveled that exist correlation between the level of education, knowledge about purpose of insurance, participation in extension course, visit with insurance organization, and contact with extension agents to the adoption of insurance by aquaculture farmers were significantly positive. By using Bartlett's test and KMO test, determine whether research variables are appropriate for factor analysis (Sig = 0.000, Bartlett test = 0.9724, KMO = 0.74). The number of factors was determined using a split plot, eigenvalue, and percent of variance. An examination of the items and their factors loadings was used to understand the nature of the nine factors. To reduce subjectivity, items with factor loading equal to or greater than 0.5 were considered most important when factors were labeled. The nine factors were labeled (1) Extension and education activities, (2) Economical characteristics, (3) Governmental support, (4) communicational channel, (5) local leaders, (6) Facilitate in given damage (7) Motivation establishing, (8) Given damage in appropriate methods and (9) Appropriate activities by insurance organization. The results obtained from the factors analysis reveal that the nine factors explain percentage75 of the variation of the adoption of insurance of the adoption of insurance by aquaculture farmers in Khuzestan province.

Keywords: aquaculture farmers, insurance, factorial analysis, Khuzestan province, risks

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813 A Dissipative Particle Dynamics Study of a Capsule in Microfluidic Intracellular Delivery System

Authors: Nishanthi N. S., Srikanth Vedantam

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Intracellular delivery of materials has always proved to be a challenge in research and therapeutic applications. Usually, vector-based methods, such as liposomes and polymeric materials, and physical methods, such as electroporation and sonoporation have been used for introducing nucleic acids or proteins. Reliance on exogenous materials, toxicity, off-target effects was the short-comings of these methods. Microinjection was an alternative process which addressed the above drawbacks. However, its low throughput had hindered its adoption widely. Mechanical deformation of cells by squeezing them through constriction channel can cause the temporary development of pores that would facilitate non-targeted diffusion of materials. Advantages of this method include high efficiency in intracellular delivery, a wide choice of materials, improved viability and high throughput. This cell squeezing process can be studied deeper by employing simple models and efficient computational procedures. In our current work, we present a finite sized dissipative particle dynamics (FDPD) model to simulate the dynamics of the cell flowing through a constricted channel. The cell is modeled as a capsule with FDPD particles connected through a spring network to represent the membrane. The total energy of the capsule is associated with linear and radial springs in addition to constraint of the fixed area. By performing detailed simulations, we studied the strain on the membrane of the capsule for channels with varying constriction heights. The strain on the capsule membrane was found to be similar though the constriction heights vary. When strain on the membrane was correlated to the development of pores, we found higher porosity in capsule flowing in wider channel. This is due to localization of strain to a smaller region in the narrow constriction channel. But the residence time of the capsule increased as the channel constriction narrowed indicating that strain for an increased time will cause less cell viability.

Keywords: capsule, cell squeezing, dissipative particle dynamics, intracellular delivery, microfluidics, numerical simulations

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812 Autoimmune Diseases Associated with Celiac Disease in Adults

Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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811 Coronin 1C and miR-128A as Potential Diagnostic Biomarkers for Glioblastoma Multiform

Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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810 Identification and Application of Biocontrol Agents against Cotton Leaf Curl Virus Disease in Gossypium hirsutum under Green House Conditions

Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

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Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

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809 The Utilization of Manganese-Enhanced Magnetic Resonance Imaging in the Fields of Ophthalmology and Visual Neuroscience

Authors: Parisa Mansour

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Understanding how vision works in both health and disease involves understanding the anatomy and physiology of the eye as well as the neural pathways involved in visual perception. The development of imaging techniques for the visual system is essential for understanding the neural foundation of visual function or impairment. MRI provides a way to examine neural circuit structure and function without invasive procedures, allowing for the detection of brain tissue abnormalities in real time. One of the advanced MRI methods is manganese-enhanced MRI (MEMRI), which utilizes active manganese contrast agents to enhance brain tissue signals in T1-weighted imaging, showcasing connectivity and activity levels. The way manganese ions build up in the eye, and visual pathways can be due to their spread throughout the body or by moving locally along axons in a forward direction and entering neurons through calcium channels that are voltage-gated. The paramagnetic manganese contrast is utilized in MRI for various applications in the visual system, such as imaging neurodevelopment and evaluating neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this assessment, we outline four key areas of scientific research where MEMRI can play a crucial role - understanding brain structure, mapping nerve pathways, monitoring nerve cell function, and distinguishing between different types of glial cell activity. We discuss various studies that have utilized MEMRI to investigate the visual system, including delivery methods, spatiotemporal features, and biophysical analysis. Based on this literature, we have pinpointed key issues in the field related to toxicity, as well as sensitivity and specificity of manganese enhancement. We will also examine the drawbacks and other options to MEMRI that could offer new possibilities for future exploration.

Keywords: glial activity, manganese-enhanced magnetic resonance imaging, neuroarchitecture, neuronal activity, neuronal tract tracing, visual pathway, eye

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808 Efficiency of Information Technology Based Learning and Teaching in Higher Educations

Authors: Mahalingam Palaniandi

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Higher education plays vital role in the nation building process for a country and the rest of world. The higher education sector develops the change-agents for the various fields which will help the human-kind wheel to run further. Conventional and traditional class-room based learning and teaching was followed in many decades which is one-to-one and one-to-many. In a way, these are simplest form of learners to be assembled in a class room wherein the teacher used the blackboard to demonstrate the theory and laboratories used for practical. As the technology evolved tremendously for the last 40 years, the teaching and learning environment changed slowly, wherein, the learning community will be anywhere in the world and teacher deliver the content through internet based tools such as video conferencing, web based conferencing tools or E-learning platforms such as Blackboard or noodle. Present day, the mobile technologies plays an important tool to deliver the teaching content on-the-go. Both PC based and mobile based learning technology brought the learning and teaching community together in various aspects. However, as the learning technology also brought various hurdles for learning processes such as plagiarism and not using the reference books entirely as most of the students wants the information instantaneously using internet without actually going to the library to take the notes from the millions of the books which are not available online as e-books which result lack of fundamental knowledge of the concepts complex theories. However, technology is inseparable in human life, now-a-days and every part of it contains piece of information technology right from computers to home appliances. To make use of the IT based learning and teaching at most efficiency, we should have a proper framework and recommendations laid to the learning community in order to derive the maximum efficiency from the IT based teaching and leaning. This paper discusses various IT based tools available for the learning community, efficiency from its usage and recommendations for the suitable framework that needs to be implemented at higher education institutions which makes the learners stronger in both theory as well as real-time knowledge of their studies that is going to be used in their future for the better world.

Keywords: higher education, e-learning, teaching learning, eLearning tools

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807 Optimization of Acid Treatments by Assessing Diversion Strategies in Carbonate and Sandstone Formations

Authors: Ragi Poyyara, Vijaya Patnana, Mohammed Alam

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When acid is pumped into damaged reservoirs for damage removal/stimulation, distorted inflow of acid into the formation occurs caused by acid preferentially traveling into highly permeable regions over low permeable regions, or (in general) into the path of least resistance. This can lead to poor zonal coverage and hence warrants diversion to carry out an effective placement of acid. Diversion is desirably a reversible technique of temporarily reducing the permeability of high perm zones, thereby forcing the acid into lower perm zones. The uniqueness of each reservoir can pose several challenges to engineers attempting to devise optimum and effective diversion strategies. Diversion techniques include mechanical placement and/or chemical diversion of treatment fluids, further sub-classified into ball sealers, bridge plugs, packers, particulate diverters, viscous gels, crosslinked gels, relative permeability modifiers (RPMs), foams, and/or the use of placement techniques, such as coiled tubing (CT) and the maximum pressure difference and injection rate (MAPDIR) methodology. It is not always realized that the effectiveness of diverters greatly depends on reservoir properties, such as formation type, temperature, reservoir permeability, heterogeneity, and physical well characteristics (e.g., completion type, well deviation, length of treatment interval, multiple intervals, etc.). This paper reviews the mechanisms by which each variety of diverter functions and discusses the effect of various reservoir properties on the efficiency of diversion techniques. Guidelines are recommended to help enhance productivity from zones of interest by choosing the best methods of diversion while pumping an optimized amount of treatment fluid. The success of an overall acid treatment often depends on the effectiveness of the diverting agents.

Keywords: diversion, reservoir, zonal coverage, carbonate, sandstone

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806 Non Chemical-Based Natural Products in the Treatment and Control of Disease in Fish

Authors: Albert P. Ekanem, Austin I. Obiekezie, Elizabeth X. Ntia

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Introduction: Some African plants and bile from animals have shown efficacies in the treatment and control of diseases in farmed fish. The background of the study is based on the fact the African rain forest is blessed with the abundance of medicinal plants that should be investigated for their use in the treatment of diseases. The significance of the study is informed by the fact that chemical-based substances accumulate in the tissues of food fish, thereby reducing the food values of such products and moreover, the continuous use of chemotherapeutics in the aquatic environments tends to degrade the affected environment. Methodology: Plants and animal products were extracted, purified and applied under in vitro and in vivo conditions to the affected organisms. Effective plants and bills were analyzed for biologically active substances responsible for the activities by both qualitative and HPLC methods. Results: Extracts of Carica papaya and Mucuna pruriens were effective in the treatment of Ichthyophthiriasis in goldfish (Carassius auratus auratus) with high host tolerance. Similarly, ectoparasitic monogeneans were effectively dislodged from the gills and skin of goldfish by the application of extracts of Piper guineense at therapeutic concentrations. Artemesia annua with known antimalarial activities in human was also effective against fish monogenean parasites of Clarias gariepinus in a concentration-related manner without detriments to the host. Effective antibacterial activities against Aeromonas and Pseudomonas diseases of the African catfish (Heterobranchus longifilis) were demonstrated in some plants such as Phylanthus amarus, Allium sativum, A. annua, and Citrus lemon. Bile from some animals (fish, goat, chicken, cow, and pig) showed great antibacterial activities against some gastrointestinal bacterial pathogens of fish. Conclusions: African plants and some animal bile have shown potential promise in the treatment of diseases in fish and other aquatic animals. The use of chemical-based substances for control of diseases in the aquatic environments should be restricted.

Keywords: control, diseases, fish, treatment

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805 Traditional Correspondence as Reminiscence Therapy for the Elderly

Authors: Paulina Pergoł, Paulina Pergoł, Tomasz Kryczka

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Aging of societies is a phenomenon that is visible all over the world. The above has social, economic, and medical consequences. Many methods of pro-health stimulation of the elderly, improving cognitive functions and quality of life, are described in the world literature. The most frequently used method of activating the elderly is physical activity, in which, in addition to standard exercise programs, activities such as dance, tai chi, and yoga are often introduced. The introduction of physical activity may be limited due to the disability that often accompanies people aged 65+. Other activating methods mentioned in the literature are therapies with the participation of animals - animal therapy or plant therapy - hortitherapy, as well as music therapy, which is increasingly popular. All of the above-mentioned therapeutic methods require the involvement of a person who would conduct the so-called occupational therapist, which can be a financial barrier for many nursing homes. Researchers all over the world are trying to find solutions that can be applied in any care institution, even in those where financial support for running such centers is small. One of the forms of therapy that is recommended in the group of elderly people and which does not require large financial outlays is the so-called reminiscence therapy based on recalling personal experiences and experiences. Thanks to reminiscence therapy, seniors can return to happy moments in their lives. Research shows that reminiscence therapy increases self-esteem and reduces symptoms of depression. The method of activating older people with the use of correspondence can be an effective and low-cost form of therapy, as shown by the pilot study conducted in 2019 as part of the Queen Silvia Nursing Award competition, consisting in a systematic exchange of correspondence between volunteers and residents of the Nursing Home. This study was conducted with the participation of a small group of participants, therefore, in order to identify and prove the beneficial effect of this form of activation, it should be carried out on a larger group of respondents using standardized scales assessing various psychological parameters.

Keywords: nursing, elderly care, psychiatry, psychology

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804 RNA-seq Analysis of Liver from NASH-HCC Model Mouse Treated with Streptozotocin-High Fat Diet

Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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803 Sodium-glucose Co-transporter-2 Inhibitors in Heart Failure with Mildly Reduced Reduced Ejection Fraction: Future Perspectives in Patients with Neoplasia

Authors: M. A. Munteanu, A. M. Lungu, A. I. Chivescu, V. Teodorescu, E. Tufanoiu, C. Nicolae, T. I. Nanea

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Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), which were first developed as antidiabetic medications, have demonstrated numerous positive benefits on the cardiovascular system, especially in the prevention of heart failure (HF). HF is a challenging, multifaceted disease that needs all-encompassing therapy. It should not be viewed as a limited form of heart illness but rather as a systemic disease that leads to multiple organ failure and death. SGLT2i is an extremely effective tool for treating HF by using its pleiotropic effects. In addition to its use in patients with diabetes mellitus who are at high cardiovascular risk or who have already experienced a cardiovascular event, SGLT2i administration has been shown to have positive effects on a variety of HF manifestations and stages, regardless of the patient's presence of diabetes mellitus. Material and Methods: According to the guide, 110 patients (83 males and 27 females) with heart failure with mildly reduced ejection fraction (HFmrEF), with T2D and neoplasia, were enrolled in the prospective study. The structural and functional state of the left ventricle myocardium and ejection fraction was assessed through echocardiography. Patients were randomized to receive once-daily dapagliflozin 10 mg. Results: Patients with HFmrEF were divided into 3 subgroups according to age. 7% (8) patients aged < 45 years, 35% (28) patients aged between 46-59 years, and 58% (74) patients aged> 60 years. The most prevalent comorbidities were hypertension (43.1%), coronary heart disease (40%), and obesity (33.2%). Study drug discontinuation and serious adverse events were not frequent in the subgroups, in either men or women, until now. Conclusions: SGLT-2 inhibitors are a novel class of antidiabetic agents that have demonstrated positive efficacy and safety outcomes in the setting of HFmrEF. Until now, in our study, dapagliflozin was safe and well-tolerated irrespective of sex.

Keywords: diabetes mellitus type 2, Sodium-glucose co-transporters-2 inhibitors, heart failure, neoplasia

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