Search results for: liver transplant candidates

Authors: Maryam Beiranvand, Sajad Yaghoubi

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Background: Some microbes can colonize plants’ inner tissues without causing obvious damage and can even produce useful bioactive substances. In the present study, the diversity of the endophytic bacteria associated with medicinal plants from Iran was investigated by culturing techniques, molecular gene identification, as well as measuring them for antibacterial activity. Results: In the spring season from 2013 to 2014, 35 herb pharmacology samples were collected, sterilized, meshed, and then cultured on selective media culture. A total of 199 endophytic bacteria were successfully isolated from 35 tissue cultures of medical plants, and sixty-seven out of 199 bacterial isolates were subjected to identification by the 16S rRNA gene sequence analysis method. Based on the sequence similarity gene and phylogenetic analyses, these isolates were grouped into five classes, fourteen orders, seventeen families, twenty-one genera, and forty strains. The most abundant group of endophytic bacteria was actinobacterial, consisting of thirty-two (47%) out of 67 bacterial isolates. Ten (22.3%) out of 67 bacterial isolates remained unidentified and classified at the genus level. The signature of the 16S rRNA gene formed a distinct line in a phylogenetic tree showing that they might be new species of bacteria. One (5.2%) out of 67 bacterial isolates was still not well categorized. Forty-two out of 67 strains were candidates for antimicrobial activity tests. Nineteen (45%) out of 42 strains showed antimicrobial activity multidrug-resistance (MDR); thirteen (68%) out of 19 strains were allocated to classes actinobacteria. Four (21%) out of 19 strains belonged to the Bacillaceae family, one (5.2%) out of 19 strains was the Paenibacillaceae family, and one (5.2%) out of 19 strains belonged to the Pseudomonadaceae family. The other twenty-three strains did not show inhibitory activities. Conclusions: Our research showed a high-level phylogenetic diversity and the intoxicating antibiotic activity of endophytic bacteria in the herb pharmacology of Iran.

Keywords: medical plant, endophytic bacteria, antimicrobial activity, whole genome sequencing analysis

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Authors: Magaya Rutendo P., Mutibvu Tonderai, Nyahangare emmanuel T., Ncube Sharai

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This study aimed to evaluate the effects of phytase and tannase addition in broiler diets on growth performance and meat quality of broilers fed sorghum-based diets. Twelve experimental diets were formulated at three sorghum levels, which include 0, 50, and 100%, and 4 enzyme levels: No enzyme, 5000FTU phytase, 25TU tannase, and a combination of 5000FTU phytase plus 25TU tannase. Data on voluntary feed intake, average weekly weight gain and feed conversion ratio were recorded and used to assess growth performance. Meat technical and nutritional parameters were used to determine meat quality. Broilers fed total sorghum diets with phytase and tannase enzyme combination had the highest feed intake in the first (24.4 ± 0.04g/bird/day) and second weeks of life (23.0 ± 1.06g/bird/day), respectively. Complete sorghum diets with phytase (83.0 ± 0.88g/bird/day) and tannase (122.0 ± 0.88g/bird/day) showed the highest feed intake in the third and fourth weeks, respectively. Broilers fed 50% sorghum diets with tannase (135.3 ± 0.05g/bird/day) and complete maize diets with phytase (158.1 ± 0.88g/bird/day) had the highest feed intake during weeks five and six, respectively. Broilers fed a 50% sorghum diet without enzymes had the highest weight gain in the final week (606.5 ± 32.39g). Comparable feed conversion was observed in birds fed complete maize and 50% sorghum diets. Dietary treatment significantly influences the live body, carcass, liver, kidneys, abdominal fat pad weight, and intestinal length. However, it did not affect Pectoralis major meat nutritional and technical parameters.

Keywords: feed efficiency, sorghum, carcass, exogenous enzymes

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

Procedia PDF Downloads 380

Authors: Brindusa Balanuca, Raluca Stan, Cristina Ott, Matei Raicopol

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The current study aims to develop anti corrosive coatings using vegetable oil (VO)-based polymers. Due to their chemical versatility, reduced costs and more important, higher hydrophobicity, VO’s are great candidates in the field of anti-corrosive materials. Lignin (Ln) derivatives were also used in this research study in order to achieve performant hydrophobic anti-corrosion layers. Methods Through a rational functionalization pathway, the selected VO (linseed oil) is converted to more reactive monomer – methacrylate linseed oil (noted MLO). The synthesized MLO cover the metals surface in a thin layer and through different polymerization techniques (using visible radiation or temperature, respectively) and well-established reaction conditions, is converted to a hydrophobic coating capable to protect the metals against corrosive factors. In order to increase the anti-corrosion protection, lignin (Ln) was selected to be used together with MLO macromonomer. Thus, super hydrophobic protective coatings will be formulated. Results The selected synthetic strategy to convert the VO in more reactive compounds – MLO – has led to a functionalization degree of greater than 80%. The obtained monomers were characterized through NMR and FT-IR by monitoring the characteristic signals after each synthesis step. Using H-NMR data, the functionalization degrees were established. VO-based and also VO-Ln anti corrosion formulations were both photochemical and thermal polymerized in specific reaction conditions (initiators, temperature range, reaction time) and were tested as anticorrosive coatings. Complete and advances characterization of the synthesized materials will be presented in terms of thermal, mechanical and morphological properties. The anticorrosive properties were also evaluated and will be presented. Conclusions Through the design strategy briefly presented, new composite materials for metal corrosion protection were successfully developed, using natural derivatives: vegetable oils and lignin, respectively.

Keywords: anticorrosion protection, hydrophobe layers, lignin, methacrylates, vegetable oil

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Authors: K. Srujana, Vinay U. Rao, M. Sudhakar

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Isoniazide (INH) a freely water soluble and pyrazinamide (Z) a practically water insoluble first line anti tubercular (TB) drugs were identified as candidates for optimizing the Moisture Activated Dry Granulation (MADG) process. The work focuses on identifying the effect of binder type and concentration as well as the effect of magnesium stearate level on critical quality attributes of Disintegration time (DT) and in vitro dissolution test when the tablets are processed by the MADG process. Also, the level of the drug concentration, binder concentration and fluid addition during the agglomeration stage of the MADG process was evaluated and optimized. For INH, it was identified that for tablets with HPMC as binder at both 2% w/w and 5% w/w level and Magnesium stearate upto 1%w/w as lubrication the DT is within 1 minute and the dissolution rate is the fastest (> 80% in 15 minutes) as compared to when PVP or pregelatinized starch is used as binder. Regarding the process, fast disintegrating and rapidly dissolving tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 25% w/w 0% w/w binder and 0.033%. w/w. At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is also slower. For pyrazinamide,it was identified that for the tablets with 2% w/w level of each of PVP as binder and Cross Caramellose Sodium disintegrant the DT is within 2 minutes and the dissolution rate is the fastest(>80 in 15 minutes)as compared to when HPMC or pregelatinized starch is used as binder. This may be attributed to the fact that PVP may be acting as a solubilizer for the practically insoluble Pyrazinamide. Regarding the process,fast dispersing and rapidly disintegrating tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 10% w/w,25% w/w binder and 1% w/w.At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is comparatively slower and less complete.

Keywords: agglomeration stage, isoniazide, MADG, moisture distribution stage, pyrazinamide

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Authors: Amberkar Mohanbabu Vittalrao, Avin, Meena Kumari Kamalkishore, Padmanabha Udupa, Vinaykumar Bavimane, Honnegouda

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Objective: To evaluate the hepato-protective activity of Tinospora cordiofolia (Tc) against paracetamol induced hepatic damage in rats. Methods: The plant stem (test drug) was procured locally, shade dried, powdered and extracted with water. Silymarin was used as standard hepatoprotective drugs and 2% gum acacia as a control (vehicle) against paracetamol (PCT) induced hepatotoxicity. Results and Discussion: The hepato-protective activity of aqueous stem extract was assessed by paracetamol induced hepatotoxicity preventive model in rats. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP and lipid peroxides were tested in both paracetamol treated and untreated groups. Paracetamol (3g/kg) had enhanced the AST, ALT, ALP and the lipid peroxides in the serum. Treatment of silymarin and aqueous stem extract of Tc (200 and 400mg/kg) extract showed significant hepatoprotective activity by altering biochemical marker levels to the near normal. Preliminary phytochemical tests were done. Aqueous Tc extract showed presence of phenolic compound and flavonoids. Our findings suggested that Tc extract possessed hepatoprotective activity in a dose dependent manner. Conclusions: Tc was found to possess significant hepatoprotective property when treated with PCT. This was evident by decreasing the liver enzymes significantly when treated with PCT as compared to PCT only treated group (P < 0.05). Hence Tinospora cardiofolia could be a good, promising, preventive agent against PCT induced hepatotoxicity.

Keywords: Tinospora cardiofolia, hepatoprotection, paracetamol, silymarin

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

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Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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Authors: Leelavinothan Pari , Ayyasamy Rathinam

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Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

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Authors: I. Elrouby

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The continued growth of tourism in the future relies on maintaining a clean environment by achieving sustainable development. The erosion and degradation of beaches, the deterioration of coastal water quality, visual pollution of coastlines by massive developments, all this has contributed heavily to the loss of the natural attractiveness for tourism. In light of this, promoting the concept of sustainable coastal development is becoming a central goal for governments and private sector. An ecolodge is a small hotel or guesthouse that incorporates local architectural, cultural and natural characteristics, promotes environmental conservation through minimizing the use of waste and energy and produces social and economic benefits for local communities. Egypt has some scattered attempts in some areas like Sinai in the field of ecolodging. This research tends to investigate the potentials of the North West Coast (NWC) in Alexandria as a new candidate for ecolodging investments. The area is full of primitive natural and man-made resources. These, if used in an environmental-friendly way could achieve cost reductions as a result of successful resource management for investors on the one hand, and coastal preservation on the other hand. In-depth interviews will be conducted with stakeholders in the tourism sector to examine their opinion about the potentials of the research area for ecolodging developments. The candidates will be also asked to rate the importance of the availability of certain environmental aspects in such establishments such as the uses of resources that originate from local communities, uses of natural power sources, uses of an environmental-friendly sewage disposal, forbidding the use of materials of endangered species and enhancing cultural heritage conservation. The results show that the area is full of potentials that could be effectively used for ecolodging investments. This if efficiently used could attract ecotourism as a supplementary type of tourism that could be promoted in Alexandria aside cultural, recreational and religious tourism.

Keywords: Alexandria, ecolodging, ecotourism, sustainability

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Authors: Fulufhelo Amanda Doboro, Kgomotso Sebeko, Stephen Njiro, Moritz Van Vuuren

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Ovine herpesvirus 2 (OvHV-2) genome obtained from the lymphopblastoid cell line of a BJ1035 cow was recently sequenced in the United States of America (USA). Information on the sequences of OvHV-2 genes obtained from South African strains from bovine or other African countries and molecular characterization of OvHV-2 is not documented. Present investigation provides information on the nucleotide and derived amino acid sequences and genetic diversity of Ov 7, Ov 8 ex2, ORF 27 and ORF 73 genes, of these genes from OvHV-2 strains circulating in South Africa. Gene-specific primers were designed and used for PCR of DNA extracted from 42 bovine blood samples that previously tested positive for OvHV-2. The expected PCR products of 495 bp, 253 bp, 890 bp and 1632 bp respectively for Ov 7, Ov 8 ex2, ORF 27 and ORF 73 genes were sequenced and multiple sequence analysis done on the selected regions of the sequenced PCR products. Two genotypes for ORF 27 and ORF 73 gene sequences, and three genotypes for Ov 7 and Ov 8 ex2 gene sequences were identified, and similar groupings for the derived amino acid sequences were obtained for each gene. Nucleotide and amino acid sequence variations that led to the identification of the different genotypes included SNPs, deletions and insertions. Sequence analysis of Ov 7 and ORF 27 genes revealed variations that distinguished between sequences from SA and reference OvHV-2 strains. The implication of geographic origin among SA sequences was difficult to evaluate because of random distribution of genotypes in the different provinces, for each gene. However, socio-economic factors such as migration of people with animals, or transportation of animals for agricultural or business use from one province to another are most likely to be responsible for this observation. The sequence variations observed in this study have no impact on the antibody binding activities of glycoproteins encoded by Ov 7, Ov 8 ex2 and ORF 27 genes, as determined by prediction of the presence of B cell epitopes using BepiPred 1.0. The findings of this study will be used for selection of gene candidates for the development of diagnostic assays and vaccine development as well.

Keywords: amino acid, genetic diversity, genes, nucleotide

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Authors: P. Bauer, K. Mougin, V. Vignal, A. Buch, P. Ponthiaux, D. Faye

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Nowadays, noble metallic nanostructures with unique morphology are widely used as new sensors due to their fascinating optical, electronic and catalytic properties. Among various shapes, dendritic nanostructures have attracted much attention because of their large surface-to-volume ratio, high sensitivity and special texture with sharp tips and nanoscale junctions. Several methods have been developed to fabricate those specific structures such as electrodeposition, photochemical way, seed-mediated growth or wet chemical method. The present study deals with a novel approach for a controlled growth pattern-directed organisation of Au flower-like crystals (NFs) deposited onto stainless steel plates to achieve large-scale functional surfaces. This technique consists in the deposition of a soft nanoporous template on which Au NFs are grown by electroplating and seed-mediated method. Size, morphology, and interstructure distance have been controlled by a site selective nucleation process. Dendritic Au nanostructures have appeared as excellent Raman-active candidates due to the presence of very sharp tips of multi-branched Au nanoparticles that leads to a large local field enhancement and a good SERS sensitivity. In addition, these structures have also been used as electrochemical sensors to detect traces of molecules present in a solution. A correlation of the number of active sites on the surface and the current charge by both colorimetric method and cyclic voltammetry of gold structures have allowed a calibration of the system. This device represents a first step for the fabrication of MEMs platform that could ultimately be integrated into a lab-on-chip system. It also opens pathways to several technologically large-scale nanomaterials fabrication such as hierarchically ordered crystal architectures for sensor applications.

Keywords: dendritic, electroplating, gold, template

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

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The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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Authors: Sheikh Omar Sillah

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Introduction: Monitoring is an important means of ensuring the smooth implementation and quality of clinical trials. For many years, traditional site monitoring approaches have been critical in detecting data errors but not optimal in identifying fabricated and implanted data as well as non-random data distributions that may significantly invalidate study results. The objective of this paper was to provide recommendations based on best statistical monitoring practices for detecting data-integrity issues suggestive of fabrication and implantation early in the study conduct to allow implementation of meaningful corrective and preventive actions. Methodology: Electronic bibliographic databases (Medline, Embase, PubMed, Scopus, and Web of Science) were used for the literature search, and both qualitative and quantitative studies were sought. Search results were uploaded into Eppi-Reviewer Software, and only publications written in the English language from 2012 were included in the review. Gray literature not considered to present reproducible methods was excluded. Results: A total of 18 peer-reviewed publications were included in the review. The publications demonstrated that traditional site monitoring techniques are not efficient in detecting data anomalies. By specifying project-specific parameters such as laboratory reference range values, visit schedules, etc., with appropriate interactive data monitoring, statistical monitoring can offer early signals of data anomalies to study teams. The review further revealed that statistical monitoring is useful to identify unusual data patterns that might be revealing issues that could impact data integrity or may potentially impact study participants' safety. However, subjective measures may not be good candidates for statistical monitoring. Conclusion: The statistical monitoring approach requires a combination of education, training, and experience sufficient to implement its principles in detecting data anomalies for the statistical aspects of a clinical trial.

Keywords: statistical monitoring, data anomalies, clinical trials, traditional monitoring

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Authors: Adela Penesova, Zofia Radikova, Boris Bajer, Andrea Havranova, Miroslav Vlcek

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Background: The aim of our study was to compare the effect of intensified lifestyle intervention on insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fibroblast growth factor (FGF) 21 after 8 weeks of lifestyle intervention. Methods: A group of 43 obese patients (13M/30F; 43.0±12.4 years; BMI (body mass index) 31.2±6.3 kg/m2 participated in a weight loss interventional program (NCT02325804) following an 8-week hypocaloric diet (-30% energy expenditure) and physical activity 150 minutes/week. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices according to Matsuda and Cederholm were calculated (ISImat and ISIced). Plasma ALT, AST, Fetuin-A, FGF 21, and physical fitness were measured. Results: The average reduction of body weight was 6.8±4.9 kg (0-15 kg; p=0.0006), accompanied with a significant reduction of body fat amount of fat mass (p=0.03), and waist circumference (p=0.02). Insulin sensitivity has been improved (IR HOMA 2.71±3.90 vs 1.24±0.83; p=0.01; ISIMat 6.64±4.38 vs 8.93±5.36 p ≤ 0.001). Total, LDL cholesterol, and triglycerides decreased (p=0.05, p=0.04, p=0.04, respectively). Physical fitness significantly improved after intervention (as measure VO2 max (maximal oxygen uptake) (p ≤ 0.001). ALT decreased significantly (0.44±0.26 vs post 0.33±0.18 ukat/l, p=0.004); however, AST not (pre 0.40±0.15 vs 0.35±0.09 ukat/l, p=0.07). Hepatokine Fetuin-A significantly decreased after intervention (43.1±10.8 vs 32.6±8.6 ng/ml, p < 0.001); however, FGF 21 levels tended to decrease (146±152 vs 132±164 pg/ml, p=0.07). Conclusion: 8-weeks of diet and physical activity intervention program in obese otherwise healthy subjects led to an improvement of insulin resistance parameters and liver marker profiles, as well as increased physical fitness. This study was supported by grants APVV 15-0228; VEGA 2/0161/16.

Keywords: obesity, diet, exercice, insulin sensitivity

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as adipogenesis, insulin resistance, and inflammation. The present study aimed to test whether supplementation with African walnuts (Aw) could have an effect on adipogenesis and others dysfunctions associated with obesity in rats. Methods: Wistar rats were fed with standard diet (SD) or high-fat high-sucrose diet (HFS) and HFS with supplemented (HFS-Aw) for eight weeks. Results: HFS diet-induced body weight gain and increased fat mass compared to SD. In addition HFS-fed rats developed fasting hyperglycaemia and insulinaemia as well as insulin resistance. Aw supplementation in HFS rats had a protective effect against adipose tissues weigh gain but slightly against body weight gain and major study related disorders. This could be mainly due to decreased food intake dependently of effect in food intake in central nervous system, which decreased in HFS rats supplemented with African walnut compared to the HFS-diet group. Interestingly, African walnut supplementation induced a slight decrease of fasting glycaemia, insulinaemia and Nitric Oxide which could partially explain its minor protective effect against diet-induced insulin resistance. Additionally a decrease in hepatic TG and transaminases levels suggesting a protective effect against liver injury. Conclusion: Taken together these data suggested that supplementation of African walnut could be used to prevent adipose weight gain and related disorders on the other hand, minimally reduced insulin resistance.

Keywords: African walnut, dietary fiber, insulin resistance, oxidative stress

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Authors: Kebret Kebede, Anthony Scinta

Abstract:

Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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Authors: Reza Eslami-Farsani, Hamed Khosravi, Saba Fayazzadeh

Abstract:

Lightweight and efficient structures have the aim to enhance the efficiency of the components in various industries. Toward this end, composites are one of the most widely used materials because of durability, high strength and modulus, and low weight. One type of the advanced composites is grid-stiffened composite (GSC) structures which have been extensively considered in aerospace, automotive, and aircraft industries. They are one of the top candidates for replacing some of the traditional components which are used here. Although there are a good number of published surveys on the design aspects and fabrication of GSC structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Matrix modification using nanoparticles is an effective method to enhance the flexural properties of the fibrous composites. In the present study, a silane coupling agent (3-glycidoxypropyltrimethoxysilane/3-GPTS) was introduced onto the silica (SiO2) nanoparticle surface and its effects on the three-point flexural response of isogrid E-glass/epoxy composites were assessed. Based on the fourier transform infrared spectrometer (FTIR) spectra, it was inferred that the 3-GPTS coupling agent was successfully grafted onto the surface of SiO2 nanoparticles after modification. Flexural test revealed an improvement of 16%, 14%, and 36% in stiffness, maximum load and energy absorption of the isogrid specimen filled with 3 wt.% 3-GPTS/SiO2 compared to the neat one. It would be worth mentioning that in these structures, a considerable energy absorption was observed after the primary failure related to the load peak. Also, 3-GPTMS functionalization had a positive effect on the flexural behavior of the multiscale isogrid composites. In conclusion, this study suggests that the addition of modified silica nanoparticles is a promising method to improve the flexural properties of the grid-stiffened fibrous composite structures.

Keywords: isogrid-stiffened composite panels, silica nanoparticles, surface modification, flexural properties, energy absorption

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Authors: Devadrita Dey Sarkar

Abstract:

Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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Authors: Binh T. T. Nguyen, Zhenyu Li, Eric Yap, Yi Zhang, Ai-Qun Liu

Abstract:

Silicon-photonic-sensor system is an emerging class of analytical technologies that use evanescent field wave to sensitively measure the slight difference in the surrounding environment. The wavelength shift induced by local refractive index change is used as an indicator in the system. These devices can be served as sensors for a wide variety of chemical or biomolecular detection in clinical and environmental fields. In our study, a system including a silicon-based micro-ring resonator, microfluidic channel, and optical processing is designed, fabricated for biomolecule detection. The system is demonstrated to detect Clostridium botulinum type A neurotoxin (BoNT) in different water sources. BoNT is one of the most toxic substances known and relatively easily obtained from a cultured bacteria source. The toxin is extremely lethal with LD50 of about 0.1µg/70kg intravenously, 1µg/ 70 kg by inhalation, and 70µg/kg orally. These factors make botulinum neurotoxins primary candidates as bioterrorism or biothreat agents. It is required to have a sensing system which can detect BoNT in a short time, high sensitive and automatic. For BoNT detection, silicon-based micro-ring resonator is modified with a linker for the immobilization of the anti-botulinum capture antibody. The enzymatic reaction is employed to increase the signal hence gains sensitivity. As a result, a detection limit to 30 pg/mL is achieved by our silicon-photonic sensor within a short period of 80 min. The sensor also shows high specificity versus the other type of botulinum. In the future, by designing the multifunctional waveguide array with fully automatic control system, it is simple to simultaneously detect multi-biomaterials at a low concentration within a short period. The system has a great potential to apply for online, real-time and high sensitivity for the label-free bimolecular rapid detection.

Keywords: biotoxin, photonic, ring resonator, sensor

Procedia PDF Downloads 117

Authors: Reza Eslami-Farsani, Hamed Khosravi, Saba Fayazzadeh

Abstract:

Lightweight and efficient structures have the aim to enhance the efficiency of the components in various industries. Toward this end, composites are one of the most widely used materials because of durability, high strength and modulus, and low weight. One type of the advanced composites is grid-stiffened composite (GSC) structures, which have been extensively considered in aerospace, automotive, and aircraft industries. They are one of the top candidates for replacing some of the traditional components, which are used here. Although there are a good number of published surveys on the design aspects and fabrication of GSC structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Matrix modification using nanoparticles is an effective method to enhance the flexural properties of the fibrous composites. In the present study, a silane-coupling agent (3-glycidoxypropyltrimethoxysilane/3-GPTS) was introduced onto the silica (SiO2) nanoparticle surface and its effects on the three-point flexural response of isogrid E-glass/epoxy composites were assessed. Based on the fourier transform infrared spectrometer (FTIR) spectra, it was inferred that the 3-GPTS coupling agent was successfully grafted onto the surface of SiO2 nanoparticles after modification. Flexural test revealed an improvement of 16%, 14%, and 36% in stiffness, maximum load and energy absorption of the isogrid specimen filled with 3 wt.% 3-GPTS/SiO2 compared to the neat one. It would be worth mentioning that in these structures, considerable energy absorption was observed after the primary failure related to the load peak. In addition, 3-GPTMS functionalization had a positive effect on the flexural behavior of the multiscale isogrid composites. In conclusion, this study suggests that the addition of modified silica nanoparticles is a promising method to improve the flexural properties of the grid-stiffened fibrous composite structures.

Keywords: isogrid-stiffened composite panels, silica nanoparticles, surface modification, flexural properties

Procedia PDF Downloads 243

Authors: Neeraj Shetye

Abstract:

A common phenomenon between the rise of leaders like Mussolini and Adolf Hitler in the 20th century is their 'charisma'. They possessed the ability to seduce the crowd not just by the things they said but also by the way they said it. Aristotle defined rhetoric as an art of persuasion and reasoning which is how social scientists understand the concept. Political rhetoric in a modern democracy has several complexities including the huge number of speakers, quantity of information, diverse viewpoints, number of candidates and the impact of digital age. Politics in India since the seventies have been 'visibly dominated' by uses of rhetorical language and with a number of slogans. This idea of how language can steer an individual to establish or adopt a certain viewpoint has not been a focus of study in the Indian discourse. In a linguistically diverse region such as India, the idea of political rhetoric is vast and may not be accomplished in a year. There are in-depth studies by western thinkers on European or American political rhetoric unlike their Asian counterparts such as China, India or any of the Pacific nations. India saw an integration of states based on languages. Keeping this idea in mind, this paper aims to cover one political party that rose to its prominence over five decades and most significantly known for its conservative expression: Shivsena. Shivsena’s rise during the eighties and eventually establishing their government in the nineties are two fascinating periods to focus especially with a simultaneous rise of Bombay underworld, Babri demolition and major economic policy changes in the form of liberalisation (1991) and globalization (1995). This project attempts to study this with a two-fold methodology: literature review and fieldwork. There is an immense literature on Shivsena by both its admirers and critiques, contributing to both sides of the debate. Scholars have been writing about this party over these years and have keenly observed its growing popularity amongst the masses. There is just one intention behind this project, and it is to connect and analyse the vast, dispersed literature that is available and contribute to a field that has not been adequately analysed in the academic discourse.

Keywords: India, language, political rhetoric, Shivsena, slogans

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Authors: Giang Ngo Tinh Nguyen

Abstract:

Agriculture plays an important role in the economy of Vietnam and coffee is one of most crucial agricultural commodities for exporting but the current farming methods and processing infrastructure could not keep up with the development of the sector. There are many catastrophic impacts on the environment such as deforestation; soil degradation that leads to a decrease in the quality of coffee beans. Therefore, improving supply chain to develop the cultivation of sustainable coffee is one of the most important strategies to boost the coffee industry and create a competitive advantage for Vietnamese coffee in the worldwide market. If all stakeholders in the supply chain network unite together; the sustainable production of coffee will be scaled up and the future of coffee industry will be firmly secured. Buon Ma Thuot city, Dak Lak province is the principal growing region for Vietnamese coffee which accounted for a third of total coffee area in Vietnam. It plays a strategically crucial role in the development of sustainable Vietnamese coffee. Thus, the research is to improve the supply chain of sustainable Vietnamese coffee production in Buon Ma Thuot city, Dak Lak province, Vietnam for the purpose of increasing the yields and export availability as well as helping coffee farmers to be more flexible in an ever-changing market situation. It will help to affirm Vietnamese coffee brand when entering international market; improve the livelihood of farmers and conserve the environment of this area. Besides, after analyzing the data, a logistic regression model is established to explain the relationship between the dependent variable and independent variables to help sustainable coffee organizations forecast the probability of farmer will be having a sustainable certificate with their current situation and help them choose promising candidates to develop sustainable programs. It investigates opinions of local farmers through quantitative surveys. Qualitative interviews are also used to interview local collectors and staff of Trung Nguyen manufacturing company to have an overview of the situation.

Keywords: supply chain management, sustainable agricultural development, sustainable coffee, Vietnamese coffee

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Authors: Bukunola K. Oguntade, Gareth M. Watkins

Abstract:

The synthesis and characterization of metal-organic frameworks (MOFs) is an area of coordination chemistry which has grown rapidly in recent years. Worldwide there has been growing concerns about future energy supplies, and its environmental impacts. A good number of MOFs have been tested for the adsorption of small molecules in the vapour phase. An important issue for potential applications of MOFs for gas adsorption and storage materials is the stability of their structure upon sorption. Therefore, study on the thermal stability of MOFs upon adsorption is important. The incorporation of two or more transition metals in a coordination polymer is a current challenge for designed synthesis. This work focused on the synthesis, characterization and small molecule adsorption properties of three microporous (one zinc monometal and two bimetallics) complexes involving Cu(II), Zn(II) and 1,2,4,5-benzenetetracarboxylic acid using the ambient precipitation and solvothermal method. The complexes were characterized by elemental analysis, Infrared spectroscopy, Scanning Electron microscopy, Thermogravimetry analysis and X-ray Powder diffraction. The N2-adsorption Isotherm showed the complexes to be of TYPE III in reference to IUPAC classification, with very small pores only capable for small molecule sorption. All the synthesized compounds were observed to contain water as guest. Investigations of their inclusion properties for small molecules in the vapour phase showed water and methanol as the only possible inclusion candidates with 10.25H2O in the monometal complex [Zn4(H2B4C)2.5(OH)3(H2O)]·10H2O but not reusable after a complete structural collapse. The ambient precipitation bimetallic; [(CuZnB4C(H2O)2]·5H2O, was found to be reusable and recoverable from structure collapse after adsorption of 5.75H2O. In addition, Solvo-[CuZnB4C(H2O)2.5]·2H2O obtained from solvothermal method show two cycles of rehydration with 1.75H2O and 0.75MeOH inclusion while structure remains unaltered upon dehydration and adsorption.

Keywords: adsorption, characterization, copper, metal -organic frameworks, zinc

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Authors: Tabassum Yasmin, Hamid Pahlevan

Abstract:

HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

Procedia PDF Downloads 196

Authors: Matej Patzelt, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Vladimir Musil, Jitka Riedlova, Viktor Sykora, Jana Mrzilkova, Petr Zach

Abstract:

Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to create a new fixation method for soft tissue imaging in micro-CT. Methodology: We used organs of 18 mice - heart, lungs, kidneys, liver and brain, which we fixated in ethanol after meticulous preparation. We fixated organs in different concentrations of ethanol and for different period of time. We used three types of ethanol concentration - 97%, 50% and ascending ethanol concentration (25%, 50%, 75%, 97% each for 12 hours). Fixated organs were scanned after 72 hours, 168 hours and 336 hours period of fixation. We scanned all specimens in micro-CT MARS (Medipix All Resolution System). Results: Ethanol method provided contrast enhancement in all studied organs in all used types of fixation. Fixation in 97% ethanol provided very fast fixation and the contrast among the tissues was visible already after 72 hours of fixation. Fixation for the period of 168 and 336 hours gave better details, especially in lung tissue, where alveoli were visualized. On the other hand, this type of fixation caused organs to petrify. Fixation in 50% ethanol provided best results in 336 hours fixation, details were visualized better than in 97% ethanol and samples were not as hard as in fixation in 97% ethanol. Best results were obtained in fixation in ascending ethanol concentration. All organs were visualized in great details, best-visualized organ was heart, where trabeculae and valves were visible. In this type of fixation, organs stayed soft for whole time. Conclusion: New ethanol method is a great option for soft tissue fixation as well as the method for enhancing contrast among tissues in organs. The best results were obtained with fixation of the organs in ascending ethanol concentration, the best visualized organ was the heart.

Keywords: x-ray imaging, small animals, ethanol, ex-vivo

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Authors: Roohallah Yousefi

Abstract:

Introduction: Voxelotor, also known as GBT 440, binds to the alpha cleft in HbS tetramers and promotes the stability of the relaxed or oxygenated state of HbS. This process hinders the conformational change of the HbS tetramers into the deoxygenated state. Voxelotor prevents interactions between HbS tetramers in the deoxygenated state, ultimately inhibiting the polymerization of HbS tetramers and resulting in significant clinical improvements, particularly in raising hemoglobin levels in patients. In this study, we have explored the use of herbal compound models, such as rosmarinic acid and compounds with similar structures that exhibit high binding affinity to Voxelotor's hemoglobin binding site. Materials and methods: The molecular model of hemoglobin (PDB: 5E83) was initially obtained from the RCSB PDB database. In addition, we collected 453 ligand models with structural similarity to rosmarinic acid from the PubChem database. To prepare these models for molecular docking, we utilized the Molegro Virtual Docker tool. Subsequently, we used the SwissADME web tool to predict the physicochemical properties and pharmacokinetics of these compounds. Results: We investigated the affinity and binding site of 453 compounds similar to rosmarinic acid on the hemoglobin model (PDB: 5E83). Our focus was on the alpha cleft between two alpha chains of the hemoglobin model (PDB: 5E83). The results showed that most compounds had molecular weights above 500 daltons, and some exhibited acceptable hydrophobicity. Furthermore, their solubility in aqueous solutions was good. None of the compounds were able to cross the blood-brain barrier or have gastrointestinal absorption. However, they did have varying inhibitory effects on CYP2C9 cytochromes. The skin penetration rate was generally low. Conclusion: Through our study, we identified three compounds (CID: 162739375, CID: 141386569, and CID: 24015539) with promising potential for further research. These compounds demonstrated high binding affinity to the hemoglobin model, favorable dissolution and digestive absorption rates, as well as suitable hydrophobicity, making them ideal candidates for continued laboratory investigation.

Keywords: voxelotor, binding site, hemoglobin, rosmarinic acid

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Authors: Devendra Gupta, S. P. Ambesh, P. K Singh

Abstract:

Introduction: Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including one lung ventilation (OLV), managing myocardial ischemia, and pain. We present an early and midterm result of the use of this technique with OLV. Method: We enrolled 62 patients for analysis operated between 2008 and 2012. Patients were anesthetized and left endobronchial tube was placed. During the procedure left lung was isolated and one lung ventilation was maintained through right lung. Operation was performed utilizing off pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Postoperative ventilation was done with single lumen endotracheal tube. Median follow-up is 2.5 years (6 months to 4 years). Results: Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 36, double vessel in 24 and triple vessel disease in 2 patients. All the patients had normal left ventricular size and function. In 2 cases difficulty were encounter in placement of endobronchial tube. In 1 case cuff of endobronchial tube was ruptured during intubation. High airway pressure was developed on OLV in 1 case and surgery was accomplished with two lung anesthesia with low tidal volume. Mean postoperative ventilation time was 14.4 hour (11-22). There was no perioperative and 30 day mortality. Conversion to median sternotomy to complete the operation was done in 3.23% (2 out of 62 patients). One patient had acute myocardial infarction postoperatively and there were no deaths during follow-up. Conclusion: MICABG is a safe and effective method of revascularization with OLV in low risk candidates for coronary artery bypass grafting.

Keywords: MIDCABG, one lung ventilation, coronary artery bypass grafting, endobronchial tube

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Authors: Samuel Oye Bandele

Abstract:

A policy is a system of principles to guide activities and strategic decisions of an organisation in order to achieve stated objectives and meeting expected outcomes. A Computer Based Test (CBT) policy is therefore a statement of intent to drive the CBT programmes, and should be implemented as a procedure or protocol. Policies are hence generally adopted by an organization or a nation. The concern here, in this paper, is the consideration and analysis of issues that are significant to evolving the acceptable policy that will drive the new CBT innovation in Nigeria. Public examinations and internal examinations in higher educational institutions in Nigeria are gradually making a radical shift from Paper Based or Paper-Pencil to Computer-Based Testing. The need to make an objective and empirical analysis of Policy issues relating to CBT became expedient. The following are some of the issues on CBT evolution in Nigeria that were identified as requiring policy backing. Prominent among them are requirements for establishing CBT centres, purpose of CBT, types and acquisition of CBT equipment, qualifications of staff: professional, technical and regular, security plans and curbing of cheating during examinations, among others. The descriptive research design was employed based on a population consisting of Principal Officers (Policymakers), Staff (Teaching and non-Teaching-Policy implementors), and CBT staff ( Technical and Professional- Policy supports) and candidates (internal and external). A fifty-item researcher-constructed questionnaire on policy issues was employed to collect data from 600 subjects drawn from higher institutions in South West Nigeria, using the purposive and stratified random sampling techniques. Data collected were analysed using descriptive (frequency counts, means and standard deviation) and inferential (t-test, ANOVA, regression and Factor analysis) techniques. Findings from this study showed, among others, that the factor loadings had significantly weights on the organizational and National policy issues on CBT innovation in Nigeria.

Keywords: computer-based testing, examination, innovation, paper-based testing, paper pencil based testing, policy issues

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