Search results for: brain tumor segmentation

Authors: Patrice L. Weiss, Barbara Mazer, Tal Krasovsky, Naomi Gefen

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Knowledge translation (KT) involves the process of applying the most promising research findings to practical settings, ensuring that new technological discoveries enhance healthcare accessibility, effectiveness, and accountability. This perspective paper aims to discuss and provide examples of how the KT process can be implemented during a time of rapid advancement in rehabilitation technologies, which have the potential to greatly influence pediatric healthcare. The analysis is grounded in a comprehensive systematic review of literature, where key studies from the past 34 years were carefully interpreted by four expert researchers in scientific and clinical fields. This review revealed both theoretical and practical insights into the factors that either facilitate or impede the successful implementation of new rehabilitation technologies. By utilizing the Knowledge-to-Action cycle, which encompasses the knowledge creation funnel and the action cycle, we demonstrated its application in integrating advanced technologies into clinical practice and guiding healthcare policy adjustments. We highlighted three successful technology applications: powered mobility, head support systems, and telerehabilitation. Moreover, we investigated emerging technologies, such as brain-computer interfaces and robotic assistive devices, which face challenges related to cost, durability, and usability. Recommendations include prioritizing early and ongoing design collaborations, transitioning from research to practical implementation, and determining the optimal timing for clinical adoption of new technologies. In conclusion, this paper informs, justifies, and strengthens the knowledge translation process, ensuring it remains relevant, rigorous, and significantly contributes to pediatric rehabilitation and other clinical fields.

Keywords: knowledge translation, rehabilitation technology, pediatrics, barriers, facilitators, stakeholders

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Authors: Ami Fadhillah Amir Abdul Nasir, Amanda C. Niehaus, Skye F. Cameron, Frank A. Von Hippel, John Postlethwait​, Robbie S. Wilson

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For suicidal breeders, the physiological stresses and energetic costs of breeding are fatal. Environmental stressors such as pollution should compound these costs, yet suicidal breeding is so rare among mammals that this is unknown. Here, we explored the consequences of metal contamination to the health, aging and performance of endangered, suicidally-breeding northern quolls (Dasyurus hallucatus) living near an active manganese mine on Groote Eylandt, Northern Territory, Australia. We found respirable manganese dust at levels exceeding international recommendations even 20km from mining sites and substantial accumulation of manganese within quolls’ hair, testes, and in two brain regions—the neocortex and cerebellum, responsible for sensory perception and motor function, respectively. Though quolls did not differ in sprint speeds, motor skill, or manoeuvrability, those with higher accumulation of manganese crashed at lower speeds during manoeuvrability tests, indicating a potential effect on sight or cognition. Immune function and telomere length declined over the breeding season, as expected with ageing, but manganese contamination exacerbated immune declines and suppressed cortisol. Unexpectedly, male quolls with higher levels of manganese had longer telomeres, supporting evidence of unusual telomere dynamics among Dasyurids—though whether this affects their lifespan is unknown. We posit that sublethal contamination via pollution, mining, or urbanisation imposes physiological costs on wildlife that may diminish reproductive success or survival.

Keywords: ecotoxicology, heavy metal, manganese, telomere length, cortisol, locomotor

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: C. C. Okafor

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The effect of different varieties of plantain (Horn, false horn and French) and fibre types (soy bean residue, cassava sievette and rice bran) on functional and organoleptic properties of plantain-based flour was assessed. Horn, false horn french were processed by washing, peeling with knife, slicing into 3mm thickness and steam blanched at 80℃ for 5minutes, oven dried at 65℃ for 48 hours and milled into flours with attrition mill, sieved with 60 mesh sieve, separately. Fibre sources were processed, milled and fractionated into 60, 40 & 20 mesh sizes. Both flours were blended as 80:20, 70:30 and 60:40. Results obtained indicated that water absorption capacity is highest (2.68) in French plantain variety irrespective of the fibre type used. And in all variety tested the swelling capacity is highest (2.93) when the plantain flour is blended with soy residue (SR) and lowest (1.25) when blended with rice brain (RB). The results show that there is significant variety and fibre type interaction effect at (P < : 0.05). Again the results showed that texture mold ability and overall acceptability were best (7.00) when soy residue was used where as addition of rice bran into plantain flour resulted in fufu with poor texture. This trend was observed in all the verities of plantain tested and in all of the particle size of flour. Using cassava serviette also yield fufu similar to that produced with soy residue in all the parameter tested (mold ability, texture and overall acceptability. Generally, plantain flours from french and false horn yielded better quality fufu in terms of texture mold ability, overall acceptability, irrespective of the fibre type used.

Keywords: functional, organoleptic, particle size, sieve mesh, variety

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Authors: Irina S. Kolesnikova, Alexander A. Dolskiy, Natalya A. Lemskaya, Yulia V. Maksimova, Asia R. Shorina, Alena S. Telepova, Alexander S. Graphodatsky, Dmitry V. Yudkin

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A cytogenetic and molecular genetic study of the family with a male child who had mental retardation and autistic features revealed an abnormal chromosome 13 bearing an enlarged p-arm with amplified ribosomal DNA (rDNA) in a boy and his father. Cytogenetic analysis using standard G-banding and FISH with labeled rDNA probes revealed an abnormal chromosome 13 with an enlarged p-arms due to rDNA amplification in a male child, who had clinically confirmed mental retardation and an autistic behavior. This chromosome is evidently inherited from the father, who has morphologically the same chromosome, but is healthy. The karyotype of the mother was normal. Ag-NOR staining showed brightly stained large whole-p-arm nucleolus organizer regions (NORs) in a child and normal-sized NORs in his father with 13p+-NOR-amount mosaicism. qRT-PCR with specific primers showed highly increased levels of 18S, 28S and 5,8 S ribosomal RNA (rRNA) in the patient’s blood samples compared to a normal healthy control donor. Both patient’s father and mother had no elevated levels of rRNAs expression. Thus, in this case, rRNA level seems to correlate with mental retardation in familial individuals with 13p+. Our findings of rRNA overexpression in a patient with mental retardation and his parents may show a possible link between the karyotype (p-arm enlargement due to rDNA amplification), rDNA functionality (rRNA overexpression), functional changes in the brain and mental retardation. The study is supported by Russian Science Foundation Grant 15-15-10001.

Keywords: mental retardation, ribosomal DNA–rDNA, ribosomal RNA–rRNA, nucleolus organizer region–NOR, chromosome 13

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Authors: M. Kouyate, M. Sangare, S. Samake, S. Keita, H. G. Kim, D. H. Geschwind

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Background & Objectives: Human genetic studies can be expensive, even unaffordable, in developing countries, partly due to the sequencing costs. Our aim is to pilot the use of bioinformatics tools to guide scientifically valid, locally relevant, and economically sound autism genetic research in Mali. Methods: The following databases, NCBI, HGMD, and LSDB, were used to identify hot point mutations. Phenotype, transmission pattern, theoretical protein expression in the brain, the impact of the mutation on the 3D structure of the protein) were used to prioritize selected autism genes. We used the protein database, Modeller, and clustal W. Results: We found Mef2c (Gly27Ala/Leu38Gln), Pten (Thr131IIle), Prodh (Leu289Met), Nme1 (Ser120Gly), and Dhcr7 (Pro227Thr/Glu224Lys). These mutations were associated with endonucleases BseRI, NspI, PfrJS2IV, BspGI, BsaBI, and SpoDI, respectively. Gly27Ala/Leu38Gln mutations impacted the 3D structure of the Mef2c protein. Mef2c protein sequences across species showed a high percentage of similarity with a highly conserved MADS domain. Discussion: Mef2c, Pten, Prodh, Nme1, and Dhcr 7 gene mutation frequencies in the Malian population will be very informative. PCR coupled with restriction enzyme digestion can be used to screen the targeted gene mutations. Sanger sequencing will be used for confirmation only. This will cut down considerably the sequencing cost for gene-to-gene mutation screening. The knowledge of the 3D structure and potential impact of the mutations on Mef2c protein informed the protein family and altered function (ex. Leu38Gln). Conclusion & Future Work: Bio-informatics will positively impact autism research in Mali. Our approach can be applied to another neuropsychiatric disorder.

Keywords: bioinformatics, endonucleases, autism, Sanger sequencing, point mutations

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Authors: Imbesat Daudi

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The United States and its allies have invaded nine countries and bombed another half a dozen in fifteen years before they ventured into Iraq. Many were Muslim countries. These invasions were illegal. Notwithstanding, invasions were justified by arguments that these countries were a danger to humanity; they either possessed weapons of mass destruction, supported terror groups or were failed states. The West also promoted that the violent behavior of Muslims stems from Islamic doctrine. Islam is associated with violence in the Western psyche, which did not evolve spontaneously but was created by neoconservative intellectuals; they were supported by the mainstream media, state institutions, and the executive and legislative branches of the United States and its allies. It resulted in an explosion of Islamophobia, which is a billion-dollar industry. This paper discusses the players and commercial interests of transnational corporations engaged, directly or otherwise, in spreading Islamophobia. The paper examines the science behind how ideas spread. Campaigns begin with the demonization of the victims with false narratives, which are based on half-truths, disinformation, and fake news. The campaigns have three phases -an initial explorative phase, which has a long lag period, an explosive phase when ideas go viral, and finally, the final phase when ideas have taken firm roots in the perception of people. Islamophobia is in its third phase. The spread of Islamophobia was based on two scientific theories: The six degrees of separation and complexity theory, which states that power stems from elements within organizations that are independent but interdependent. Ideas once established in the human brain cannot be easily dislodged, which explains why brilliant minds are having a difficult time resisting Islamophobia. Islamophobia is a menace to humanity; it should be resisted. However, one must understand how Islamophobia spreads and why it is difficult to dislodge fake narratives associated with Islamophobia.

Keywords: Islamophobia, demonization of Islam, dehumanization of Muslims

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Authors: Palaniyandi Karuppaiya, Hsin Sheng Tsay, Fang Chen

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Medicinal herbs do represent a huge and noteworthy reservoir for novel anticancer drugs discovery. Dysosma pleiantha (Hance) Woodson (Berberidaceae), one of the oldest traditional Chinese medicinal herb, highly prized by the mountain tribes of Taiwan and China for its medicinal properties contained pharmaceutically important antitumor compounds podophyllotoxin, quercetin and kaempferol. Among lignans, podophyllotoxin is an active antitumor compound and has now been modified to produce clinically useful drugs etoposide and teniposide. In recent years, natural populations of D. peliantha have declined considerably due to anthropogenic activities such as habitat destruction and commercial exploitation for medicinal applications. As to its overall conservation status, D. pleiantha has been ranked as threatened on the China Species Red List. In the present study, an efficient in vitro callus culture system of D. pleiantha was established on Gamborg’s medium with various combinations and concentrations of different auxins and cytokinins under dark condition. Best callus induction was recorded in 2 mg/L 2, 4 - Dichlorophenoxyacetic acid (2,4-D) along with 0.2 mg/L kinetin and the maximum callus proliferation was achieved at 1 mg/L 2,4-D. Among the explants tested, maximum callus induction (86 %) was achieved from tender leaves. Hence, in subsequent experiments, leaf callus was further investigated for suitable callus biomass and production level of anticancer compounds under the influence of different additives. A maximum fresh callus biomass (8.765 g) was recorded in callus proliferation medium contained 500 mg/L casein hydrolysate. High performance liquid chromatography results revealed that the addition of different concentrations of peptone (1, 2 and 4 g/L) in callus proliferation medium enhanced podophyllotoxin (16 fold), quercetin (12 fold) and kaempferol (5 fold) accumulation than control. Thus, the established in vitro callus culture under the influence of different additives may offer an alternative source of enhanced production of podophyllotoxin, kaempferol and quecertin without harming natural plant population.

Keywords: dysosma pleiantha, kaempferol, podophyllotoxin, quercetin

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Authors: Abdulbaset Mazarzaei

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Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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Authors: Olajumoke Temilola Fatimat, Fasasi Fausat Kikelomo, Ishola Ganiyat Folasayo, Omayeka Mary

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Psychoactive substances are chemical substances that affect the normal functioning of the brain and cause changes in behavior, mood, and consciousness. Psychoactive substance abuse constitutes one of the most important risk–taking behavior among adolescents and young adults in secondary schools. The study, therefore, assessed the factors influencing the use of psychoactive substances among senior secondary students in Ibadan South–West Local Government Area, Oyo State. A descriptive non-experimental design was adopted; purposive and simple random sampling techniques were used to select 330 respondents, while questionnaires were used for data collection. The descriptive statistics of frequency count, percentages, inferential statistics of chi-square, and analysis of variance were used for the analysis. The results revealed that the majority of the respondents had heard of the term substance abuse before 226 (75.3%); it was also revealed that the majority of the respondents had good knowledge of psychoactive substances, 67.8%. There was no significant relationship between age and knowledge of psychoactive substances among senior secondary students, with a p-value of 0.199. The outcome of this study indicates that drug abuse is increasing day by day among secondary school students and may have greatly contributed to poor performance in examinations as well as undermining academic ability and performance among students. It was recommended that efforts should be made by the school authorities of the secondary schools in Ibadan South–West Local Government Area, Oyo State, and in Oyo State generally in collaboration with health personnel to educate adolescents on psychoactive substance abuse. This is to ensure that adolescents are adequately educated and updated on knowledge of psychoactive substance abuse.

Keywords: factors, influence, psychoactive substance, secondary school

Procedia PDF Downloads 71

Authors: David Polcari, Samuel C. Perry, Loredano Pollegioni, Matthias Geissler, Janine Mauzeroll

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ᴅ-serine acts as an endogenous co-agonist for N-methyl-ᴅ-aspartate receptors in neuronal synapses. This makes it a key component in the development and function of a healthy brain, especially given its role in several neurodegenerative diseases such as Alzheimer’s disease and dementia. Despite such clear research motivations, the primary site and mechanism of ᴅ-serine release is still currently unclear. For this reason, we are developing a biosensor for the detection of ᴅ-serine utilizing a microelectrode in combination with a ᴅ-amino acid oxidase enzyme, which produces stoichiometric quantities of hydrogen peroxide in response to ᴅ-serine. For the fabrication of a biosensor with good selectivity, we use a permselective poly(meta-phenylenediamine) film to ensure only the target molecule is reacted, according to the size exclusion principle. In this work, we investigated the effect of the electrodeposition conditions used on the biosensor’s response time and selectivity. Careful optimization of the fabrication process allowed for enhanced biosensor response time. This allowed for the real time sensing of ᴅ-serine in a bulk solution, and also provided in means to map the efflux of ᴅ-serine in real time. This was done using scanning electrochemical microscopy (SECM) with the optimized biosensor to measure localized release of ᴅ-serine from an agar filled glass capillary sealed in an epoxy puck, which acted as a model system. The SECM area scan simultaneously provided information regarding the rate of ᴅ-serine flux from the model substrate, as well as the size of the substrate itself. This SECM methodology, which provides high spatial and temporal resolution, could be useful to investigate the primary site and mechanism of ᴅ-serine release in other biological samples.

Keywords: ᴅ-serine, enzymatic biosensor, microelectrode, scanning electrochemical microscopy

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Authors: Shalini Adiga, Shashikant Chetty, Jisha, Shobha Kamath

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Background: Moderate impairment of learning and memory has been observed in both type 1 and 2 diabetes mellitus in humans and experimental animals. A Change in glucose utilization and oxidative stress that occur in diabetes are considered the main reasons for cognitive dysfunction. Objective: Costus igneus (CI) which is known to possess hypoglycemic activity was evaluated in this study for its effect on learning and memory in normal and diabetic rats. Methods: Wistar rats were divided into control, CI-alcoholic extract treated normal (250 and 500mg/kg), diabetic control and CI-treated diabetic groups. CI treatment was continued for 4 weeks. For induction of diabetes, a single dose of streptozotocin was injected (30 mg/kg i.p). Entrance latency and time spent in the dark room during acquisition and at 24 and 48h after an aversive shock in a passive avoidance model was used as an index of learning and memory. Glutathione and malondialdehyde levels in brain and blood glucose were measured. Data was analysed using ANOVA. Results: During the three trials in exploration test, the diabetic control rats exhibited no significant change in entrance latency or in the total time spent in the dark compartment. During retention testing, the entrance latency of the diabetic treated groups was two times less at 24h and three times less at 48h after aversive stimulus as compared to diabetic rats. The normal drug-treated rats showed similar behaviour as the saline control. Treatment with CI significantly reduced the raised blood sugar and MDA levels of diabetic rats. Conclusion: Costus igneus prevented the cognitive dysfunction in diabetic rats which can be attributed to its antioxidant and antihyperglycemic activities.

Keywords: Costus igneous, diabetes, learning and memory, cognitive dysfunction

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Daniel F. Madrinan-Chiquito

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Hemiparesis affects about eight out of ten stroke survivors, causing weakness or the inability to move one side of the body. One-sided weakness can affect arms, hands, legs, or facial muscles. People with one-sided weakness may have trouble performing everyday activities such as eating, cooking, dressing, and using the bathroom. Rehabilitation treatments, exercises at home, and assistive devices can help with mobility and recovery. Historically, such treatments and devices were developed within the fields of medicine and biomedical engineering. However, innovators outside of the traditional medical device community, such as Industrial Designers, have recently brought their knowledge and expertise to assistive technologies. Primary and secondary research was done in three parts. The primary research collected data by talking with several occupational therapists currently attending to stroke patients, and surveys were given to patients with hemiparesis and hemiplegia. The secondary research collected data through observation and testing of products currently marketed for single-handed people. Modern kitchenware available in the market for people with an acquired brain injury has deficiencies in both aesthetic and functional values. Object design for people with hemiparesis or hemiplegia has not been meaningfully explored. Most cookware is designed for use with two hands and possesses little room for adaptation to the needs of one-handed individuals. This project focuses on the design and development of two kitchenware devices. These devices assist hemiparetics with different cooking-related tasks such as holding, grasping, cutting, slicing, chopping, grating, and other essential activities. These intentionally designed objects will improve the quality of life of hemiparetics by enabling greater independence and providing an enhanced ability for precision tasks in a cooking environment.

Keywords: assistive technologies, hemiparetics, industrial design, kitchenware

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Authors: Supasak Ngaoprasertwong

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The purpose of this research was to develop a model for Muay Thai competition management for promoting sport tourism in the next decade. Moreover, the model was appropriately initiated for practical use. This study also combined several methodologies, both quantitative research and qualitative research, to entirely cover all aspects of data, especially the tourists’ satisfaction toward Muay Thai competition. The data were collected from 400 tourists watching Muay Thai competition in 4 stadiums to create the model for Muay Thai competition to support the sport tourism in the next decade. Besides, Ethnographic Delphi Futures Research (EDFR) was applied to gather the data from certain experts in boxing industry or having significant role in Muay Thai competition in both public sector and private sector. The first step of data collection was an in-depth interview with 27 experts associated with Muay Thai competition, Muay Thai management, and tourism. The second step and the third step of data collection were conducted to confirm the experts’ opinions toward various elements. When the 3 steps of data collection were completely accomplished, all data were assembled to draft the model. Then the model was proposed to 8 experts to conduct a brainstorming to affirm it. According to the results of quantitative research, it found that the tourists were satisfied with personnel of competition at high level (x=3.87), followed by facilities, services, and safe high level (x=3.67). Furthermore, they were satisfied with operation in competition field at high level (x=3.62).Regarding the qualitative methodology including literature review, theories, concepts and analysis of qualitative research development of the model for Muay Thai competition to promote the sport tourism in the next decade, the findings indicated that there were 2 data sets as follows: The first one was related to Muay Thai competition to encourage the sport tourism and the second one was associated with Muay Thai stadium management to support the sport tourism. After the brain storming, “EE Muay Thai Model” was finally developed for promoting the sport tourism in the next decade (2015-2024).

Keywords: Muay Thai competition management, Muay Thai sport tourism, Muay Thai, Muay Thai for sport tourism management

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Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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Authors: Sanja O. Podunavac-Kuzmanović, Strahinja Z. Kovačević, Lidija R. Jevrić

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Prion is a protein substance whose certain form is considered as infectious agent. It is presumed to be the cause of the transmissible spongiform encephalopathies (TSEs). The protein it is composed of, called PrP, can fold in structurally distinct ways. At least one of those 3D structures is transmissible to other prion proteins. Prions can be found in brain tissue of healthy people and have certain biological role. The structure of prions naturally occurring in healthy organisms is marked as PrPc, and the structure of infectious prion is labeled as PrPSc. PrPc may play a role in synaptic plasticity and neuronal development. Also, it may be required for neuronal myelin sheath maintenance, including a role in iron uptake and iron homeostasis. PrPSc can be considered as an environmental pollutant. The main aim of this study was to carry out the molecular modeling and calculation of molecular descriptors (lipophilicity, physico-chemical and topological descriptors) of structurally diverse compounds which can be considered as anti-prion agents. Molecular modeling was conducted applying ChemBio3D Ultra version 12.0 software. The obtained 3D models were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. The Austin Model 1 (AM-1) was used for full geometry optimization of all structures. The obtained set of molecular descriptors is applied in analysis of similarities and dissimilarities among the tested compounds. This study is an important step in further development of quantitative structure-activity relationship (QSAR) models, which can be used for prediction of anti-prion activity of newly synthesized compounds.

Keywords: chemometrics, molecular modeling, molecular descriptors, prions, QSAR

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Authors: Ruphi Naz, Altaf Ahmad, Mohammad Anis

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Sialic acid (5-Acetylneuraminic acid, Neu5Ac) is a common sugar found as a terminal residue on glycoconjugates in many animals. Humans brain and the central nervous system contain the highest concentration of sialic acid (as N-acetylneuraminic acid) where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis. Due to its important biological function, sialic acid is attracting increasing attention. To understand metabolic networks, fluxes and regulation, it is essential to be able to determine the cellular and subcellular levels of metabolites. Genetically-encoded fluorescence resonance energy transfer (FRET) sensors represent a promising technology for measuring metabolite levels and corresponding rate changes in live cells. Taking this, we developed a genetically encoded FRET (fluorescence resonance energy transfer) based nanosensor to analyse the sialic acid level in living cells. Sialic acid periplasmic binding protein (sia P) from Haemophilus influenzae was taken and ligated between the FRET pair, the cyan fluorescent protein (eCFP) and Venus. The chimeric sensor protein was expressed in E. coli BL21 (DE3) and purified by affinity chromatography. Conformational changes in the binding protein clearly confirmed the changes in FRET efficiency. So any change in the concentration of sialic acid is associated with the change in FRET ratio. This sensor is very specific to sialic acid and found stable with the different range of pH. This nanosensor successfully reported the intracellular level of sialic acid in bacterial cell. The data suggest that the nanosensors may be a versatile tool for studying the in vivo dynamics of sialic acid level non-invasively in living cells

Keywords: nanosensor, FRET, Haemophilus influenzae, metabolic networks

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Authors: Gaurav Bhanjana, Ganga Ram Chaudhary, Sandeep Kumar, Neeraj Dilbaghi

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Main sources of endocrine disrupting compounds in the ecosystem are hormones, pesticides, phthalates, flame retardants, dioxins, personal-care products, coplanar polychlorinated biphenyls (PCBs), bisphenol A, and parabens. These endocrine disrupting compounds are responsible for learning disabilities, brain development problems, deformations of the body, cancer, reproductive abnormalities in females and decreased sperm count in human males. Although discharge of these chemical compounds into the environment cannot be stopped, yet their amount can be retarded through proper evaluation and detection techniques. The available techniques for determination of these endocrine disrupting compounds mainly include high performance liquid chromatography (HPLC), mass spectroscopy (MS) and gas chromatography-mass spectrometry (GC–MS). These techniques are accurate and reliable but have certain limitations like need of skilled personnel, time consuming, interference and requirement of pretreatment steps. Moreover, these techniques are laboratory bound and sample is required in large amount for analysis. In view of above facts, new methods for detection of endocrine disrupting compounds should be devised that promise high specificity, ultra sensitivity, cost effective, efficient and easy-to-operate procedure. Nowadays, electrochemical sensors/biosensors modified with nanomaterials are gaining high attention among researchers. Bioelement present in this system makes the developed sensors selective towards analyte of interest. Nanomaterials provide large surface area, high electron communication feature, enhanced catalytic activity and possibilities of chemical modifications. In most of the cases, nanomaterials also serve as an electron mediator or electrocatalyst for some analytes.

Keywords: electrochemical, endocrine disruptors, microscopy, nanoparticles, sensors

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Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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Authors: Ramuel Spirituel Mattathiah A. San Juan, Neil Ambasing

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Background: In lateral medullary strokes, hemiparesis doesn't typically manifest due to the distinct vascular supply to the corticospinal tract located within the medulla's tegmentum. Hemiparesis resulting from a medullary infarct would likely be attributable to a medial medullary stroke characterized by contralateral hemiparesis since the corticospinal tract fibers at this level have yet to cross over. This paper reports a unique case of a lateral medullary stroke variant that presented with ipsilateral hemiparesis. Objective: There have only been 23 other cases of reported Opalski syndrome, making this only the 24th and 25th case reported worldwide. Case Presentation: A 53-year-old male was admitted with slurring of speech with gait instability, numbness on the right face, Horner’s syndrome, and 4/5 motor strength on the right extremities. Hyperreflexia was noted on the right, together with a Babinski’s sign. Cranial magnetic resonance imaging (MRI) showed an infarct on the right dorsolateral medulla. A 48-year-old male was admitted complaining of dizziness, ataxic gait, veering to the left during ambulation, left facial numbness, left hemiplegia, crossed sensory disturbance, and right limb ataxia. MRI revealed an acute left lateral medullary infarction. Conclusion: A rare type of lateral medullary infarction, the Opalski Syndrome, is a weakness ipsilateral to the lesion of the infarct. The lesion involves the ipsilateral corticospinal tract below the pyramidal decussation. The considerable diversity in the posterior brain circulation serves as a contributing factor to the clinical observation of incomplete textbook syndromes, underscoring the significance of the neurological clinical approach and a solid foundation in neuroanatomy.

Keywords: Opalski syndrome, rare stroke, stroke, Wallenberg's syndrome

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Authors: Justyna Humięcka-Jakubowska

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1. Background in music analysis. Traditionally, when we think about a composer’s sketches, the chances are that we are thinking in terms of the working out of detail, rather than the evolution of an overall concept. Since music is a “time art’, it follows that questions of a form cannot be entirely detached from considerations of time. One could say that composers tend to regard time either as a place gradually and partially intuitively filled, or they can look for a specific strategy to occupy it. In my opinion, one thing that sheds light on Stockhausen's compositional thinking is his frequent use of 'form schemas', that is often a single-page representation of the entire structure of a piece. 2. Background in music technology. Sonic Visualiser is a program used to study a musical recording. It is an open source application for viewing, analysing, and annotating music audio files. It contains a number of visualisation tools, which are designed with useful default parameters for musical analysis. Additionally, the Vamp plugin format of SV supports to provide analysis such as for example structural segmentation. 3. Aims. The aim of my paper is to show how SV may be used to obtain a better understanding of the specific musical work, and how the compositional strategy does impact on musical structures and musical surfaces. I want to show that ‘traditional” music analytic methods don’t allow to indicate interrelationships between musical surface (which is perceived) and underlying musical/acoustical structure. 4. Main Contribution. Stockhausen had dealt with the most diverse musical problems by the most varied methods. A characteristic which he had never ceased to be placed at the center of his thought and works, it was the quest for a new balance founded upon an acute connection between speculation and intuition. In the case with Mikrophonie I (1964) for tam-tam and 6 players Stockhausen makes a distinction between the "connection scheme", which indicates the ground rules underlying all versions, and the form scheme, which is associated with a particular version. The preface to the published score includes both the connection scheme, and a single instance of a "form scheme", which is what one can hear on the CD recording. In the current study, the insight into the compositional strategy chosen by Stockhausen was been compared with auditory image, that is, with the perceived musical surface. Stockhausen's musical work is analyzed both in terms of melodic/voice and timbre evolution. 5. Implications The current study shows how musical structures have determined of musical surface. My general assumption is this, that while listening to music we can extract basic kinds of musical information from musical surfaces. It is shown that an interactive strategies of musical structure analysis can offer a very fruitful way of looking directly into certain structural features of music.

Keywords: automated analysis, composer's strategy, mikrophonie I, musical surface, stockhausen

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

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Authors: N. V. Kazmiruk, Y. R. Nartsissov

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Phosphate activated glutaminase (GA, E.C. 3.5.1.2) plays a key role in glutamine/glutamate homeostasis in mammalian brain, catalyzing the hydrolytic deamidation of glutamine to glutamate and ammonium ions. GA is mainly localized in mitochondria, where it has the catalytically active form on the inner mitochondrial membrane (IMM) and the other soluble form, which is supposed to be dormant. At present time, the exact localization of the membrane glutaminase active site remains a controversial and an unresolved issue. The first hypothesis called c-side localization suggests that the catalytic site of GA faces the inter-membrane space and products of the deamidation reaction have immediate access to cytosolic metabolism. According to the alternative m-side localization hypothesis, GA orients to the matrix, making glutamate and ammonium available for the tricarboxylic acid cycle metabolism in mitochondria directly. In our study, we used a multi-compartment kinetic approach to simulate metabolism of glutamate and glutamine in the astrocytic cytosol and mitochondria. We used physiologically important ratio between the concentrations of glutamine inside the matrix of mitochondria [Glnₘᵢₜ] and glutamine in the cytosol [Glncyt] as a marker for precise functioning of the system. Since this ratio directly depends on the mitochondrial glutamine carrier (MGC) flow parameters, key observation was to investigate the dependence of the [Glnmit]/[Glncyt] ratio on the maximal velocity of MGC at different initial concentrations of mitochondrial glutamate. Another important task was to observe the similar dependence at different inhibition constants of the soluble GA. The simulation results confirmed the experimental c-side localization hypothesis, in which the glutaminase active site faces the outer surface of the IMM. Moreover, in the case of such localization of the enzyme, a 3-fold decrease in ammonium production was predicted.

Keywords: glutamate metabolism, glutaminase, kinetic approach, mitochondrial membrane, multi-compartment modeling

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Authors: Arsalan Ansari, Muhammad Dawood Idrees, Maria Hafeez

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Use of mobile phones has been increasing considerably over the past decade. Currently, it is one of the main sources of communication and information. Initially, mobile phones were limited to calls and messages, but with the advent of new technology smart phones were being used for many other purposes including video games. Despite of positive outcomes, addiction to video games on mobile phone has become a leading cause of psychological and physiological problems among many people. Several researchers examined the different aspects of behavior addiction with the use of different scales. Objective of this study is to examine any distinction between mobile game addicted and non-addicted players with the use of electroencephalography (EEG), based upon psycho-physiological indicators. The mobile players were asked to play a mobile game and EEG signals were recorded by BIOPAC equipment with AcqKnowledge as data acquisition software. Electrodes were places, following the 10-20 system. EEG was recorded at sampling rate of 200 samples/sec (12,000samples/min). EEG recordings were obtained from the frontal (Fp1, Fp2), parietal (P3, P4), and occipital (O1, O2) lobes of the brain. The frontal lobe is associated with behavioral control, personality, and emotions. The parietal lobe is involved in perception, understanding logic, and arithmetic. The occipital lobe plays a role in visual tasks. For this study, a 60 second time window was chosen for analysis. Preliminary analysis of the signals was carried out with Acqknowledge software of BIOPAC Systems. From the survey based on CGS manual study 2010, it was concluded that five participants out of fifteen were in addictive category. This was used as prior information to group the addicted and non-addicted by physiological analysis. Statistical analysis showed that by applying clustering analysis technique authors were able to categorize the addicted and non-addicted players specifically on theta frequency range of occipital area.

Keywords: mobile game, addiction, psycho-physiology, EEG analysis

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Authors: S. Jurado, E. Pazmino

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Determination of the medial axis of a porous media sample is a non-trivial problem of interest for several disciplines, e.g., hydrology, fluid dynamics, contaminant transport, filtration, oil extraction, etc. However, the computational tools available for researchers are limited and restricted. The primary aim of this work was to develop a series of algorithms to extract porosity, medial axis structure, and pore-throat size distributions from porous media domains. A complementary objective was to provide the algorithms as free computational software available to the academic community comprising researchers and students interested in 3D data processing. The burn algorithm was tested on porous media data obtained from High-Resolution X-Ray Microtomography (HRXMT) and idealized computer-generated domains. The real data and idealized domains were discretized in voxels domains of 550³ elements and binarized to denote solid and void regions to determine porosity. Subsequently, the algorithm identifies the layer of void voxels next to the solid boundaries. An iterative process removes or 'burns' void voxels in sequence of layer by layer until all the void space is characterized. Multiples strategies were tested to optimize the execution time and use of computer memory, i.e., segmentation of the overall domain in subdomains, vectorization of operations, and extraction of single burn layer data during the iterative process. The medial axis determination was conducted identifying regions where burnt layers collide. The final medial axis structure was refined to avoid concave-grain effects and utilized to determine the pore throat size distribution. A graphic user interface software was developed to encompass all these algorithms, including the generation of idealized porous media domains. The software allows input of HRXMT data to calculate porosity, medial axis, and pore-throat size distribution and provide output in tabular and graphical formats. Preliminary tests of the software developed during this study achieved medial axis, pore-throat size distribution and porosity determination of 100³, 320³ and 550³ voxel porous media domains in 2, 22, and 45 minutes, respectively in a personal computer (Intel i7 processor, 16Gb RAM). These results indicate that the software is a practical and accessible tool in postprocessing HRXMT data for the academic community.

Keywords: medial axis, pore-throat distribution, porosity, porous media

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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