Search results for: nucleoside analogue

Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

Procedia PDF Downloads 107

Authors: Phuoc Si Nguyen

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Infinite impulse response (IIR) filters can be designed from an analogue low pass prototype by using frequency transformation in the s-domain and bilinear z-transformation with pre-warping frequency; this method is known as frequency transformation from the s-domain to the z-domain. This paper will introduce a new method to transform an IIR digital filter to another type of IIR digital filter (low pass, high pass, band pass, band stop or narrow band) using a technique based on inverse bilinear z-transformation and inverse matrices. First, a matrix equation is derived from inverse bilinear z-transformation and Pascal’s triangle. This Low Pass Digital to Digital Filter Pascal Matrix Equation is used to transform a low pass digital filter to other digital filter types. From this equation and the inverse matrix, a Digital to Digital Filter Pascal Matrix Equation can be derived that is able to transform any IIR digital filter. This paper will also introduce some specific matrices to replace the inverse matrix, which is difficult to determine due to the larger size of the matrix in the current method. This will make computing and hand calculation easier when transforming from one IIR digital filter to another in the digital domain.

Keywords: bilinear z-transformation, frequency transformation, inverse bilinear z-transformation, IIR digital filters

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Authors: Giorgi Chichinadze, David Shengelia, Tamara Tsutsunava, Nikoloz Maisuradze, Giorgi Beridze

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The Jalovchat intrusive is built up of hornblende gabbros, gabbro-norites and norites. Within the intrusive hornblende-bearing gabbro-pegmatites are widespread. That is a coarse-grained rock with gigantic hornblende crystals. By its unusual composition, the Jalovchat intrusive has no analogue in the Caucasus. However, petrologically and geochemically, the intrusive rocks were studied insufficiently. For comprehensive investigations, the authors applied appropriate methodologies: Microscopic study of thin sections, petro- and geochemical analyses of the samples and also different petrogenic, rare and rare earth elements diagrams and spidergrams. Analytical study established that the Jalovchat intrusive by its composition corresponds mainly to the mid-ocean ridge basalts and according to geodynamic type belongs to the subduction type. In general, it is an anomalous phenomenon, as in the rocks of such composition crystallization of hornblende and especially of its gigantic crystals is atypical. The authors believe that the water-rich magma reservoir, which was necessary for the crystallization of gigantic hornblende crystals, appeared as a result of melting of water-rich mid-ocean ridge basaltic rocks during the subduction process in Bajocian time.

Keywords: gabbro-pegmatite, intrusive, petrogenesis, petrogeochemistry, the Caucasus

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Authors: Clara Theresia, Hardianto Iridiastadi

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Drowsiness is one of the main factors that contribute to the occurrence of accidents, particularly in the transportation sector. While the effects of sleep deprivation on cognitive functions have been reported, the exact relationships remain a critical issue. This study aimed at quantifying the effects of extreme sleep deprivation on vigilance, fatigue, and performance during simulated train driving. A total of 12 participants were asked to drive a train simulator continuously for 4 hours, either in a sleep deprived condition (2-hr of sleep) or normal (8-hr of sleep) condition. Dependent variables obtained during the task included Psychomotor Vigilance Task (PVT) parameters, degree of fatigue (assessed via Visual Analogue Scale/VAS) and sleepiness (reported using Karolinska Sleepiness Scale/KSS), and driving performance (the number of speed limit violations). Findings from this study demonstrated substantial decrements in vigilance in the sleep-deprived condition. This condition also resulted in 75% increase in speed violation and a two-fold increase in the degree of fatigue and sleepiness. Extreme sleep deprivation was clearly associated with substantially poorer response. The exact effects, however, were dependent upon the types of responses.

Keywords: cognitive function, psychomotor vigilance task, sleep deprivation, train simulator

Procedia PDF Downloads 181

Authors: Daniel Todorov, Anton Hinkov, Petya Angelova, Kalina Shishkova, Venelin Tsvetkov, Stoyan Shishkov

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Human herpes viruses (HHV) are ubiquitous pathogens with a pandemic spread across the globe. HHV type 1 is the main causative agent of cold sores and fever blisters around the mouth and on the face, whereas HHV type 2 is generally responsible for genital herpes outbreaks. The treatment of both viruses is more or less successful with antivirals from the nucleoside analogues group. Their wide application increasingly leads to the emergence of resistant mutants In the past, medicinal plants have been used to treat a number of infectious and non-infectious diseases. Their diversity and ability to produce the vast variety of secondary metabolites according to the characteristics of the environment give them the potential to help us in our warfare with viral infections. The variable chemical characteristics and complex composition is an advantage in the treatment of herpes since the emergence of resistant mutants is significantly complicated. The screening process is difficult due to the lack of standardization. That is why it is especially important to follow the mechanism of antiviral action of plants. On the one hand, it may be expected to interact with its compounds, resulting in enhanced antiviral effects, and the most appropriate environmental conditions can be chosen to maximize the amount of active secondary metabolites. During our study, we followed the activity of various plant extracts on the viral replication cycle as well as their effect on the extracellular virion. We obtained our results following the logical sequence of the experimental settings - determining the cytotoxicity of the extracts, evaluating the overall effect on viral replication and extracellular virion.During our research, we have screened a variety of plant extracts for their antiviral activity against both virus replication and the virion itself. We investigated the effect of the extracts on the individual stages of the viral replication cycle - viral adsorption, penetration and the effect on replication depending on the time of addition. If there are positive results in the later experiments, we had studied the activity over viral adsorption, penetration and the effect of replication according to the time of addition. Our results indicate that some of the extracts from the Lamium album have several targets. The first stages of the viral life cycle are most affected. Several of our active antiviral agents have shown an effect on extracellular virion and adsorption and penetration processes. Our research over the last decade has shown several curative antiviral plants - some of which are from the Lamiacea family. The rich set of active ingredients of the plants in this family makes them a good source of antiviral preparation.

Keywords: human herpes virus, antiviral activity, Lamium album, Nepeta nuda

Procedia PDF Downloads 153

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

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Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

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Authors: Andrey Norov

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In the recent years, Samoilov Research Institute for Mineral Fertilizers JSC “NIUIF”, the oldest (established in September 1919) industry-oriented institute in Russia, has developed a range of sustainable, environment-friendly, zero-waste technologies that ensure minimal consumption of materials and energy resources and fully consistent with the principles of Green Chemistry that include: - Ecofriendly energy and resource saving technology of sulfuric acid from sulfur according to DC-DA scheme (double conversion - double absorption); - Improved zero-waste technology of wet phosphoric acid (WPA) by dihydrate-hemihydrate process applicable to various types of phosphate raw materials; - Flexible, efficient, zero-waste, universal technology of NP / NPS / NPK / NPKS fertilizers with maximum heat recovery from chemical processes; - Novel, zero-waste, no-analogue technology of granular PK / PKS / NPKS fertilizers with controlled dissolution rate and nutrient supply into the soil, which allows to process a number of wastes and by-products; - Innovative resource-saving joint processing of wastes from the production of phosphogypsum and fluorosilicic acid (FSA) into ammonium sulfate with simultaneous neutralization of fluoride compounds with no lime used. - New fertilizer technology of increased environmental and agrochemical efficiency (currently under development). All listed green technologies are patented with Russian and Eurasian patents. The development of ecofriendly, safe, green technologies is ongoing in JSC “NIUIF”.

Keywords: NPKS fertilizers, FSA, sulfuric acid, WPA

Procedia PDF Downloads 92

Authors: Minas Balyan

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In the third-order nonlinear Takagi’s equations for monochromatic waves and in the third-order nonlinear time-dependent dynamical diffraction equations for X-ray pulses for forbidden reflections the Fourier-coefficients of the linear and the third order nonlinear susceptibilities are zero. The dynamical diffraction in the nonlinear case is related to the presence in the nonlinear equations the terms proportional to the zero order and the second order nonzero Fourier coefficients of the third order nonlinear susceptibility. Thus in the third order nonlinear Bragg diffraction case a nonlinear analogue of the well known Renninger effect takes place. In this work, the ‘third order nonlinear Renninger effect’ is considered theoretically and numerically. If the reflection exactly is forbidden the diffracted wave’s amplitude is zero both in Laue and Bragg cases since the boundary conditions and dynamical diffraction equations are compatible with zero solution. But in real crystals due to some percent of dislocations and other localized defects, the atoms are displaced with respect to their equilibrium positions. Thus in real crystals susceptibilities of forbidden reflection are by some order small than for usual not forbidden reflections but are not exactly equal to zero. The numerical calculations for susceptibilities two order less than for not forbidden reflection show that in Bragg geometry case the nonlinear reflection curve’s behavior is the same as for not forbidden reflection, but for forbidden reflection the rocking curves’ width, center and boundaries are two order sensitive on the input intensity value. This gives an opportunity to investigate third order nonlinear X-ray dynamical diffraction for not intense beams – 0.001 in the units of critical intensity.

Keywords: third order nonlinearity, Bragg diffraction, nonlinear Renninger effect, rocking curves

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Authors: Versha Sharma

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Juvenile hormone analogue, fenoxycarb and ecdysterone, when applied at varying concentrations in the adult females of Dysdercus similis, in situ histochemical observations of treated ovarian and adipose tissues during the first gonotrophic cycle elicited drastic histomorphological changes in both tissues. The action and effect of both JHa and ecdysterone on ovarian development, vitellogenesis, the activity of follicular epithelium, chorion formation all were monitored in detail. SDS-PAGE electrophoretic analysis showed drastic downregulation on the protein profile of differently treated tissue samples. After exogenous JHa supply, resorption of the developing oocytes was also often noticed. Gradational decline and disappearance of different protein bands in treated both ovarian and adipose tissues noticed could be due to the depletion of specific metabolites essential for oocyte development and maturation. Natural products support both crop production and the environment that being effective in pest control, less toxic to non-target organisms and at the same time biodegradable. Hence, these could be utilized as an attractive alternative to the synthetic chemical insecticides for at least cotton bug pest management. Increasing IGR dosages is found to elicit both qualitative and quantitative depletion of protein metabolites and drastic histochemical changes in the gonads of the treated forms brought forth the production of a large number of immature mal-formed oocytes. Findings in greater detail could be discussed.

Keywords: juvenile hormone, ecdysone, P. picta, Dysdercus similis

Procedia PDF Downloads 247

Authors: Bheeshma B., Mathivanan N., Manoj Deepak M., Prabhu Thangaraju, K. Venkatachalam

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This study involves the effect of autologous blood injection for patients who had degeneration of the origin of extensor carpi radialis brevis which was confirmed radio logically and by ultrasound examination and failed cortisone injections to the lateral epicondylitis. In this prospective longitudinal series involves pre-injection assessment of grip strength, pain, and function, using the patient-rated tennis elbow evaluation. In this study, blood from the contralateral limb is taken and injected into the affected limb with the help of ultrasound guidance and then the patient wore a customized wrist support for five days, after which they were commenced with stretching, strengthening, and massage programme with an occupational therapist. In these patients assessment was done after six months and then finally at 12 months after injection, using the patient-rated tennis elbow evaluation. 50 patients completed the study, showing significant improvement in pain; the worst pain decreased by two to five points out of a 10-point visual analogue for pain. Self-perceived function improved by 11–25 points out of 100. Women showed significant increase in grip, but men did not. Our study thus concludes that autologous blood injection show significant improvement in pain and function in patients with chronic lateral epicondylitis, who did not have relief with cortisone injection.

Keywords: lateral epicondylitis, autologous blood injection, conservative treatment, plasma-rich proteins (PRPs)

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Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 155

Authors: Mahshid Rezaei, Zahra Tajari, Zahra Esmaeily, Atefeh Eyvazkhani, Shahrzad Daei, Marjan Mansouri Dara, Mohaddesh Rezaei, Abolghassem Djazayeri, Ahmadreza Dorosti Motlagh

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Background: Musculoskeletal pain is one of the most prevalent symptoms in elderly age. Nutrition and diet are considered important underlying factors that could affect chronic musculoskeletal pain. The purpose of this study was to identify the relationship between empirical dietary inflammatory patterns (EDII) and musculoskeletal pain. Method: In this cross-sectional study, 213 elderly individuals were selected from several health centers. The usual dietary intake was evaluated by a valid and reliable 147-items food frequency questionnaire (FFQ). To measure the intensity of pain, Visual Analogue Scale (VAS) was used. Multiple Linear Regression was applied to assess the association between EDII and musculoskeletal pain. Results: The results of multiple linear regression analysis indicate that a higher EDII score was associated with higher musculoskeletal pain (β= 0.21: 95% CI: 0.24-1.87: P= 0.003). These results stayed significant even after adjusting for covariates such as sex, marital status, height, family number, sleep, BMI, physical activity duration, waist circumference, protector, and medication use (β= 0.16: 95% CI: 0.11-1.04: P= 0.02). Conclusion: Study findings indicated that higher inflammation of diet might have a direct association with musculoskeletal pains in elderlies. However, further investigations are required to confirm these findings.

Keywords: musculoskeletal pain, empirical dietary inflammatory pattern, elderlies, dietary pattern

Procedia PDF Downloads 201

Authors: Tim Nikolsky

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This paper seeks to explore the different ways in which music producers choose to embrace various levels of technology based on musical values, objectives, affordability, access and workflow benefits. Current digital audio production workflow is questioned. Engineers and music producers of today are increasingly divorced from the tangibility of music production. Making music no longer requires you to reach over and turn a knob. Ideas of authenticity in music production are being redefined. Calculations from the mathematical algorithm with the pretty pictures are increasingly being chosen over hardware containing transformers and tubes. Are mouse clicks and movements equivalent or inferior to the master brush strokes we are seeking to conjure? We are making audio production decisions visually by constantly looking at a screen rather than listening. Have we compromised our music objectives and values by removing the ‘hands-on’ nature of music making? DAW interfaces are making our musical decisions for us not necessarily in our best interests. Technological innovation has presented opportunities as well as challenges for education. What do music production students actually need to learn in a formalised education environment, and to what extent do they need to know it? In this brave new world of omnipresent music creation tools, do we still need tangibility in music production? Interviews with prominent Australian music producers that work in a variety of fields will be featured in this paper, and will provide insight in answering these questions and move towards developing an understanding how tangibility can be rediscovered in the next generation of music production.

Keywords: analogue, digital, digital audio workstation, music production, plugins, tangibility, technology, workflow

Procedia PDF Downloads 268

Authors: Y. S. Darmanto, P. H. Riyadi, S. Susanti

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Recently, approximately 9.1 million people of 237.56 million of Indonesian population suffer diabetes. Such condition was caused by high rice consumption of most Indonesian people. It has been known that rice contains low amylose, high calorie, and possesses hyperglycemic properties. Through this study, we tried to solve that problem by creating a super food in order to provide an alternative healthy and balanced diet. We formulated Taro and Seaweed flour based analog rice that fortified by various fishes bone collagens. Corms of Taro contain easily digestible starch and seaweed is rich in fiber, vitamin, and mineral. That mixture was fortified with collagen-containing unique amino acids such as glysine, lysine, alanine, arginine, proline, and hydroxyprolin. Subsequently, super analog rice was characterized about its nutritional composition such are proximate analyses, water, dietary fiber and amylose content. Furthermore, its morphological structure was analyzed by using scanning electron microscopy while the level of consumer preferences was performed by hedonic test. Results demonstrated that fortification by using various fishes bone collagen into analog rice were significantly different in nutritional composition, morphological structure as well as its preferences. Thus, this study was expected as new avenue in functional food discovery especially in the treatment and prevention of diabetic diseases.

Keywords: analogue rice, taro, seaweed, collagen

Procedia PDF Downloads 262

Authors: Marzieh Yassin, Fereshteh Navaee, Javad Sarrafzadeh, Reza Salehi

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Introduction: Myofascial trigger point (MTrP) is one of the most common sources of musculoskeletal pain. Approximately 30-85% of the patients with musculoskeletal pains would experience MTrP in their life. The prevalence of MTrP has reported in the patients seen in a general orthopedic clinic, general medical clinic and specialty pain management centers, 21%, 30% and 93% respectively. Nowadays, dry needling is suggested as a standard treatment for MTrPs. The purpose of the present study was to examine the effectiveness of dry needling with stretching upper trapezius muscle on pain and pain pressure threshold in participants with active myofascial trigger point. Methods: Thirty participants with an active myofascial trigger point of the upper trapezius muscle were randomly divided into two groups: dry needling with passive stretch (n=15) and passive stretch alone (n=15). They received 5 sessions of the treatments for three weeks. The outcomes were pain intensity and pain pressure threshold that were assessed with visual analogue scale and algometer respectively. Results: Significant improvement in pain and pain pressure threshold was observed in both groups (P=0.0001) after the treatment. Also, the results showed a significant difference in measurements between two groups (P<0.05). Conclusion: Dry needling with passive stretch can be more effective on pain and pain pressure threshold than passive stretching alone in short term in participants with active myofascial trigger points.

Keywords: dry needling, myofascial pain syndrome, myofascial trigger point, stretching

Procedia PDF Downloads 58

Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and have been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. However, very little information is currently available for their mechanism. The prikly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, southwestern region of Korea, and used as a functional food. Present study investigated the effects of OFS on pancreatic β-cell function using pancreatic islet β cells (HIT cell). Alpha-glucosidase inhibition, glucose uptake, insulin secretion, insulin sensitivity, and pancreatic β cell proliferation were determined. The inhibitory effect of ethanol extract of OFS stem on α-glucosidase enzyme was measured in a cell free system. Glucose uptake was determined using fluorescent glucose analogue, 2-NBDG. Insulin secretion was measured by ELISA assay. Cell proliferation was measured by MTT assay. Ethanol extracts of OFS dose-dependently inhibited α-glucosidase activity as well as glucose uptake. Insulinotrophic effect of OFS extract was observed at high glucose media in pancreatic β-islet cells. Furthermore, pancreatic β cell regeneration was also observed.These results suggest that OFS mediates the antidiabetic activity mainly via α-glucosidase inhibition, glucose uptake, and improved insulin sensitivity.

Keywords: prickly pear cactus, Opuntia ficus-indica var. Saboten, pancreatic islet HIT cells, α-glucosidase, glucose uptake, insulinotrophic

Procedia PDF Downloads 457

Authors: Bentayeb-Ait Lounis Saïda, Cheref Zahia, Cherifi Thizi, Ri Kahina Bahmed, Kahina Hallali Yasmine Abdellaoui, Kenza Adli

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Algeria is the leading consumer of dairy products in North Africa. This is a fact. However, the nutritional quality of the latter remains unknown. The aim of this study is to characterise the dairy products available on the Algerian market in order to assess whether they constitute a healthy and safe choice. To do this, it collected data on the labelling of 390 dairy products, including cheese, yoghurt, UHT milk and milk drinks, infant formula and dairy creams. We assessed their degree of processing according to the NOVA classification, as well as the proportion of imitation products. The study was carried out between March 2020 and August 2023. The results show that 88% are ultra-processed; 84% for 'cheese', 92% for dairy creams, 92% for 'yoghurt', 100% for infant formula, 92% for margarines and 36% for UHT milk/dairy drinks. As for imitation/analogue dairy products, the study revealed the following proportions: 100% for infant formula, 78% for butter/margarine, 18% for UHT milk/milk-based drinks, 54% for cheese, 2% for camembert and 75% for dairy cream. The harmful effects of consuming ultra-processed products on long-term health are increasingly documented in dozens of publications. The findings of this study sound the alarm about the health risks to which Algerian consumers are exposed. Various scientific, economic and industrial bodies need to be involved in order to safeguard consumer health in both the short and long term. Food awareness and education campaigns should be organised.

Keywords: dairy, UPF, NOVA, yoghurt, cheese

Procedia PDF Downloads 28

Authors: Oluibukun G. Ajayi, Joseph O. Odumosu, Oladimeji T. Babafemi, Azeez Z. Opeyemi, Asaleye O. Samuel

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The need for the complete automation of every procedure of surveying and most especially, its engineering applications cannot be overemphasized due to the many demerits of the conventional manual or analogue approach. This paper presents the summarized details of the development of a Route Information Management (RIM) software. The software, codenamed ‘AutoROUTE’, was encoded using Microsoft visual studio-visual basic package, and it offers complete automation of the computational procedures and plan production involved in route surveying. It was experimented using a route survey data (longitudinal profile and cross sections) of a 2.7 km road which stretches from Dama to Lunko village in Minna, Niger State, acquired with the aid of a Hi-Target DGPS receiver. The developed software (AutoROUTE) is capable of computing the various simple curve parameters, horizontal curve, and vertical curve, and it can also plot road alignment, longitudinal profile, and cross-section with a capability to store this on the SQL incorporated into the Microsoft visual basic software. The plotted plans with AutoROUTE were compared with the plans produced with the conventional AutoCAD Civil 3D software, and AutoROUTE proved to be more user-friendly and accurate because it plots in three decimal places whereas AutoCAD plots in two decimal places. Also, it was discovered that AutoROUTE software is faster in plotting and the stages involved is less cumbersome compared to AutoCAD Civil 3D software.

Keywords: automated systems, cross sections, curves, engineering construction, longitudinal profile, route surveying

Procedia PDF Downloads 141

Authors: Enas El Sayed Abutaleb, Mohamed Taher Eldesoky, Shahenda Abd El Rasol

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Background: Muscle energy techniques (MET) have been widely used by manual therapists over the past years, but still limited research validated its use and there was limited evidence to substantiate the theories used to explain its effects. Objective: To investigate the effect of muscle energy technique (MET) on anterior pelvic tilt in patients with lumbar spondylosis. Design: Randomized controlled trial. Subjects: Thirty patients with anterior pelvic tilt from both sexes were involved, aged between 35 to 50 years old and they were divided into MET and control groups with 15 patients in each. Methods: All patients received 3 sessions/week for 4 weeks where the study group received MET, Ultrasound and Infrared, and the control group received U.S and I.R only. Pelvic angle was measured by palpation meter, pain severity by the visual analogue scale and functional disabilities by the Oswestry disability index. Results: Both groups showed significant improvement in all measured variables. The MET group was significantly better than the control group in pelvic angle, pain severity, and functional disability as p-value were (0.001, 0.0001, 0.0001) respectively. Conclusion and implication: The study group fulfilled greater improvement in all measured variables than the control group which implies that application of MET in combination with U.S and I.R were more effective in improving pelvic tilting angle, pain severity and functional disabilities than using electrotherapy only.

Keywords: anterior pelvic tilt, lumbar spondylosis, muscle energy technique exercise, pelvic tilting angle

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Authors: Gregory Chown, Benjamin Infantolino, Christopher Wise, Rachel Holmes, Samantha O'Donnell, Katelyn Pfeiffer, Victoria Ward

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Background: There is a lack of understanding of how Kinesio Tape® physiologically works. Furthermore, few studies compare Kinesio Tape® to other forms of taping. The research question is: Does Kinesio Tape® cause a difference in muscle facilitation, inhibition, and pain, between Kinesio Tape® and no tape for collegiate athletes with self-reported shoulder pain? Method: This quantitative non-randomized design used a convenience sampling method. There were eleven participants with self-reported shoulder pain who were athletes on the men’s and women’s lacrosse and tennis teams. Participants attended one 30-45 minute session for data collection. Each participant received all three taping conditions and performed four repetitions of 120 degrees of active shoulder flexion for the three separate trials (no tape, Kinesio Tape® inhibition, and Kinesio Tape® facilitation). Surface electromyography (sEMG) electrodes were placed on the anterior deltoid, supraspinatus, and lower trapezius to measure muscle facilitation and inhibition. Each participant completed the visual analogue scale (VAS) before and after each trial to measure pain. Results: No statistical significance was found for pain scores on the VAS between the taping methods of facilitation, inhibition, and no tape (p = .118). No statistical significance was found for the percentage of change in muscle function for each taping method; Anterior deltoid (p = .993), supraspinatus (p = .997) and lower trapezius (p = .922). Conclusion: Based on the results, Kinesio Tape® appears to not have an effect on muscle function or pain when utilizing the facilitation or inhibition taping method when compared to no tape.

Keywords: Kinesio tape, muscle facilitation, muscle inhibition, pain

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Authors: Andrew Fife, Jean-Francois Esculier, Codi Ramsey, Kim Hebert-Losier

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Objectives: We aimed to identify how an evidence-based educational video influences how runners select shoes, and perceive shoe comfort, satisfaction, and performance over three months in comparison with a control video. Design: Two groups participated in a double-blind randomised controlled trial. Method: Fifty-six runners were randomly assigned to view one of two video presentations prior to purchasing new shoes for road running in speciality stores. Runners completed a survey with regards to their own shoes and one in reference to the new shoes purchased at three timepoints: before first use, onemonth post-purchase, and three-months post-purchase. Perceived shoe comfort, satisfaction, and performance were assessed using 100 mm visual analogue scales. Factors that influenced their shoe purchase were ranked in order of importance. Results: Comfort and satisfaction were not significantly different between groups and timepoints. The perceived performance of new shoes (75.6 mm) was significantly greater than own shoes (mean: 67.6 mm) before first use, but ratings returned to own-shoe levels one month later in both groups. The group receiving the evidence-based presentation reported their purchased shoes as being influenced more by the video (55.4 mm) than the control group (21.8 mm), although both chose the same brand and model as previously worn over half of the time. Runners in both groups prioritised fit, comfort, and choosing similar shoes to the ones they previously used. Conclusions: In contrast to expectations, the evidence-based educational video did not appear to influence running shoe selection, or overall perceived shoe comfort, satisfaction, or performance.

Keywords: comfort, consumer behaviour, consciousness, education, running, shoes

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Authors: Mohamed M. Diab, Koura G. Mohamed, A. Balbaa, Radwan Sh. Ahamed

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Background: Chronic mechanical low back pain (CMLBP) is the most common complaint of the working-age population. Mechanical low back pain is often a chronic, dull, aching pain of varying intensity that affects the lower spine. In the current proposal the hip rotation-CMLBP relationship is based on that limited hip motion will be compensated by motion in the lumbopelvic region and this increase force translates to the lumbar spine. The purpose of this study was to investigate if there a relationship between chronic mechanical low back pain (CMLBP) and hip medial and lateral rotation (peak torque and Range of motion (ROM) in patients with CMLBP. Methods: Sixty patients with CMLBP diagnosed by an orthopedist participated in the current study after signing a consent form. Their mean of age was (23.76±2.39) years, mean of weight (71.8±12.7) (Kg), mean of height (169.65±7.49) (Cm) and mean of BMI (25.5±3.86) (Kg/m2). Visual Analogue Scale (VAS) was used to assess pain. Fluid Filled Inclinometer was used to measure Hip rotation ROM (medial and lateral). Isokinetic Dynamometer was used to measure peak torque of hip rotators muscles (medial and lateral), concentric peak torque with tow Isokinetic speeds (60ᵒ/sec and 180ᵒ/sec) was selected to measure peak torque. Results: The results of this study demonstrated that there is poor relationship between pain and hip external rotation ROM, also there is poor relation between pain and hip internal rotation ROM. There is poor relation between pain and hip internal rotators peak torque and hip external rotators peak torque in both speeds. Conclusion: Depending on the current study it is not recommended to give an importance to hip rotation in treating Chronic Mechanical Low Back Pain.

Keywords: hip rotation ROM, hip rotators strength, low back pain, chronic mechanical

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Authors: Vladyslav Povoroznyuk, Tetiana Orlуk, Nataliia Dzerovych

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Introduction: Back pain is an extremely common health care problem worldwide. Many studies show a link between an obesity and risk of lower back pain. The aim is to study correlation and peculiarities of vertebral pain in women of different age depending on their anthropometric indicators. Materials: 1886 women aged 25-89 years were examined. The patients were divided into groups according to age (25-44, 45-59, 60-74, 75-89 years old) and body mass index (BMI: to 18.4 kg/m2 (underweight), 18.5-24.9 kg/m2 (normal), 25-30 kg/m2 (overweight) and more than 30.1 kg/m2 (obese). Methods: The presence and intensity of pain was evaluated in the thoracic and lumbar spine using a visual analogue scale (VAS). BMI is calculated by the standard formula based on body weight and height measurements. Statistical analysis was performed using parametric and nonparametric methods. Significant changes were considered as p <0.05. Results: The intensity of pain in the thoracic spine was significantly higher in the underweight women in the age groups of 25-44 years (p = 0.04) and 60-74 years (p=0.005). The intensity of pain in the lumbar spine was significantly higher in the women of 45-59 years (p = 0.001) and 60-74 years (p = 0.0003) with obesity. In the women of 45-74 years BMI was significantly positively correlated with the level of pain in the lumbar spine. Obesity significantly increases the relative risk of pain in the lumbar region (RR=0.07 (95% CI: 1.03-1.12; p=0.002)), while underweight significantly increases the risk of pain in the thoracic region (RR=1.21 (95% CI: 1.00-1.46; p=0.05)). Conclusion: In women, vertebral pain syndrome may be related to the anthropometric characteristics (e.g., BMI). Underweight may indirectly influence the development of pain in the thoracic spine and increase the risk of pain in this part by 1.21 times. Obesity influences the development of pain in the lumbar spine increasing the risk by 1.07 times.

Keywords: body mass index, age, pain in thoracic and lumbar spine, women

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Authors: Ossama Salman

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Background and objective: Sacroiliac joint pain is a common cause for chronic axial low back pain, with up to 20% prevalence rate. To date, no effective long-term treatment intervention has been embarked on yet. The aim of our study was to compare steroid block to radiofrequency ablation for SIJ pain conditions. Methods: A randomized, blind, study was conducted in 30 patients with sacroiliac joint pain. Fifteen patients received radiofrequency denervation of L4-5 primary dorsal rami and S1-3 lateral sacral branch, and 15 patients received steroid under fluoroscopy. Those in the steroid group who did not respond to steroid injections were offered to cross over to get radiofrequency ablation. Results: At 1-, 3- and 6-months post-intervention, 73%, 60% and 53% of patients, respectively, gained ≥ 50 % pain relief in the radiofrequency (RF) ablation group. In the steroid group, at one month post intervention follow up, only 20% gained ≥ 50 % pain relief, but failed to show any improvement at 3 months and 6 months follow up. Conclusions: Radiofrequency ablation at L4 and L5 primary dorsal rami and S1-3 lateral sacral branch may provide effective and longer pain relief compared to the classic intra-articular steroid injection, in properly selected patients with suspected sacroiliac joint pain. Larger studies are called for to confirm our results and lay out the optimal patient selection and treatment parameters for this poorly comprehended disorder.

Keywords: lateral branch denervation, LBD, radio frequency, RF, sacroiliac joint, SIJ, visual analogue scale, VAS

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Muhammad A. Muhammad

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Butenafine (N-4-tert-butyl benzyl-N-methyl-1-naphthylene methylamine hydrochloride) is a benzylamine antimycotic (antifungal) agent that has a broad spectrum of action. The quest for improved antimycotic action brought about many research on the structure-activity properties of butenafine in relation to other antifungal agents. Of all those research, only little or no effort was recorded on the substituents attached to the aromatic systems in butenafine. In this research, N-(4-(tert-butyl) benzyl)-1-(4-tert-butyl) phenyl)-N-methyl methanaminium chloride, which is a butenafine analogue was synthesised from tert-butyl benzyl derivatives, by reductive amination using various solvents through a direct approach, where 1,2-dichloroethane gave the best solvent action at 40 °C (Yield: 75%) and of all the reducing agents used, sodium borohydride was found to give the best reducing action in the presence of silica chloride at room temperature (Yield: 50%). Characterization of the compound by 1H NMR showed a singlet peak of 18 hydrogen atoms with a chemical shift at 1.3-1.5 ppm for the presence of 6 methyl groups in the two tert-butyl substituents, the 13C NMR also indicated the presence of the two tert-butyl substituents by the peak with a chemical shift at 31-32 ppm for the six methyl carbon atoms, the IR indicated the presence of a tertiary ammonium ion by a strong band at 2460 cm-1 and finally the EIS-MS confirmed the molar mass of the compound by a mass to charge ratio of 324.2693. These results suggested that the target molecule was actually synthesised and therefore, 1,2-dichloroethane is a good solvent for this synthesis, and the most suitable reducing agent is sodium borohydride.

Keywords: antimicrobial agents, antimycotic agents, butenafine, chemotherapeutic agents, semisynthetic agents

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Sedef Şahin, Meral Huri

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Cerebral Palsy (CP) represents the most frequent cause of physical disability in children with a rate of 2,9 per 1000 live births. The activity-focused intervention is known to improve function and reduce activity limitations and barriers to participation of children with disabilities. The aim of the study was to assess the effects of occupational therapy on level of fatigue, activity performance and satisfaction in children with Unilateral Cerebral Palsy. Twenty-two children with hemiparetic cerebral palsy (mean age: 9,3 ± 2.1years; Gross Motor Function Classification System ( GMFCS) level from I to V (I = 54%, II = 23%, III = 14%, IV= 9%, V= 0%), Manual Ability Classification System (MACS) level from I to V (I = 40%, II = 32%, III = 14%, IV= 10%, V= 4%), were assigned to occupational therapy program for 6 weeks.Visual Analogue Scale (VAS) was used for intensity of the fatigue they experienced at the time on a 10 point Likert scale (1-10).Activity performance and satisfaction were measured with Canadian Occupational Performance Measure (COPM).A client-centered occupational therapy intervention was designed according to results of COPM. The results were compared with nonparametric Wilcoxon test before and after the intervention. Thirteen of the children were right-handed, whereas nine of the children were left handed.Six weeks of intervention showed statistically significant differences in level of fatigue, compared to first assessment(p<0,05). The mean score of first and the second activity performance scores were 4.51 ± 1.70 and 7.35 ± 2.51 respectively. Statistically significant difference between performance scores were found (p<0.01). The mean scores of first and second activity satisfaction scores were of 2.30± 1.05 and 5.51 ± 2.26 respectively. Statistically significant difference between satisfaction assessments were found (p<0.01). Occupational therapy is an evidence-based approach and occupational therapy interventions implemented by therapists were clinically effective on severity of fatigue, activity performance and satisfaction if implemented individually during 6 weeks.

Keywords: activity performance, cerebral palsy, fatigue, occupational therapy

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

Abstract:

The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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