Search results for: theme progression

Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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Authors: Toby Gibbs, Glen Craigie, Suwaree Yordchim

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Using the Speexx Online Language Training Program with Thai students has allowed us to evaluate their learning comprehension and track their progression through the English language program. Speexx sets the standard for excellence and innovation in web-based language training and online coaching services. The program is designed to improve the business communication skills of language learners for Thai students. Speexx consists of English lessons, exercises, tests, web boards, and supplementary lessons to help students practice English. The sample groups are 191 Thai sophomores studying Business English with the department of Humanities and Social Science. The data was received by standard deviation (S.D.) value from questionnaires and samples provided from the Speexx training program. The results found that most Thai sophomores fail the Speexx training program due to their learning comprehension of the English language is below average. With persisted efforts on new training methods, the success of the Speexx Language Training Program can break through the cultural barriers and help future students adopt English as a second language. The Speexx results revealed four main factors affecting the success as follows: 1) Future English training should be pursued in applied Speexx development. 2) Thai students didn’t see the benefit of having an Online Language Training Program. 3) There is a great need to educate the next generation of learners on the benefits of Speexx within the community. 4) A great majority of Thai Sophomores didn't know what Speexx was. A guideline for self-reliance planning consisted of four aspects: 1) Development planning: by arranging groups to further improve English abilities with the Speexx Language Training program and encourage using Speexx every day. Local communities need to develop awareness of the usefulness of Speexx and share the value of using the program among family and friends. 2) Humanities and Social Science staff should develop skills using this Online Language Training Program to expand on the benefits of Speexx within their departments. 3) Further research should be pursued on the Thai Students progression with Speexx and how it helps them improve their language skills with Business English. 4) University’s and Language centers should focus on using Speexx to encourage learning for any language, not just English.

Keywords: ability, comprehension, sophomore, speexx

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Sangchul Kim, Dosaeng Park

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It is one of the important design issues to provide various levels of difficulty in order to suit the skillfulness of an individual. In this paper we propose an integer programming-based method for selecting a mixture of challenges for a racing game that meet a given degree of difficulty. The proposed method can also be used to dynamically adjust the difficulty of the game during the progression of playing. By experiments, it is shown that our method performs well enough to generate games with various degrees of difficulty that match the perception of players.

Keywords: level generation, level adjustment, racing game, ip

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Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

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Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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Authors: Zuliani Mahmood, Thirumulu Ponnuraj Kannan, Yean Yean Chan, Salahddin A. Al-Hudhairy

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Caries is the most common childhood disease which develops due to disturbances in the physiological equilibrium in the dental plaque resulting in demineralization of tooth structures. Plaque and dentine samples were collected from three different tooth surfaces representing caries progression (intact, over carious lesion and dentine) in children with early childhood caries (ECC, n=36). In caries free (CF) children, plaque samples were collected from sound tooth surfaces at baseline and after one year (n=12). The genomic DNA was extracted from all samples and subjected to 16S rRNA PCR amplification. The end products were cloned into pCR®2.1-TOPO® Vector. Five randomly selected positive clones collected from each surface were sent for sequencing. Identification of the bacterial clones was performed using BLAST against GenBank database. In the ECC group, the frequency of Lactobacillus sp. detected was significantly higher in the dentine surface (p = 0.031) than over the cavitated lesion. The highest frequency of bacteria detected in the intact surfaces was Fusobacterium nucleatum subsp. polymorphum (33.3%) while Streptococcus mutans was detected over the carious lesions and dentine surfaces at a frequency of 33.3% and 52.7% respectively. Fusobacterium nucleatum subsp. polymorphum was also found to be highest in the CF group (41.6%). Follow up at the end of one year showed that the frequency of Corynebacterium matruchotii detected was highest in those who remained caries free (16.6%), while Porphyromonas catoniae was highest in those who developed caries (25%). In conclusion, Streptococcus mutans and Porphyromonas catoniae are strongly associated with caries progression, while Lactobacillus sp. is restricted to deep carious lesions. Fusobacterium nucleatum subsp. polymorphum and Corynebacterium matruchotii may play a role in sustaining the healthy equilibrium in the dental plaque. These identified bacteria show promise as potential biomarkers in diagnosis which could help in the management of dental caries in children.

Keywords: early childhood caries, genotypic identification, oral bacteria, 16S rRNA

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Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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Authors: Ali Yaro Kankia

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Millennium Development Goals are eight goals set by the 189 United Nations member States with 2015 as its target year of achievement. Since its signing in September 2000, individual nations have been finding ways and means of actualizing them. This paper consider how a refocused basic Mathematics curriculum could serve as an appropriate tool in achieving these goals. This was done by considering the theme in the following sub-headings. Basic Mathematics curriculum before now, basic Mathematics curriculum and the millennium development Goals and challenges of a refocused basic Mathematics curriculum for the MDGs. The appropriate conclusion was reached.

Keywords: actualizing, curriculum, MDGs, refocused

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Authors: Shideh Mohseni Movahed, Mansoureh Safari

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Intelligent drug delivery systems (IDDS) are innovative technological innovations and clinical way to advance current treatments. These systems differ in technique of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require different pharmacological therapies. IDDS capable of releasing an active molecule at the proper site and at a amount that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism is particularly appealing. In this paper, we describe the most recent advances in the development of intelligent drug delivery systems.

Keywords: drug delivery systems, IDDS, medicine, health

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Randall E. Osborne

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A four-step ‘humanities’ thought model has been used in an interdisciplinary course for almost two decades and has been proven to aid in student abilities to become more inclusive in their world view. Lack of tolerance for ambiguity can interfere with this progression so we developed an assignment that seems to have assisted students in developing more tolerance for ambiguity and, therefore, opened them up to make more progress on the critical thought model. A four-step critical thought model (built from a humanities education approach) is used in an interdisciplinary course on prejudice, discrimination, and hate in an effort to minimize egocentrism and promote sociocentrism in college students. A fundamental barrier to this progression is a lack of tolerance for ambiguity. The approach to the course is built on the assumption that Tolerance for Ambiguity (characterized by a dislike of uncertain, ambiguous or situations in which expected behaviors are uncertain, will like serve as a barrier (if tolerance is low) or facilitator (if tolerance is high) of active ‘engagement’ with assignments. Given that active engagement with course assignments would be necessary to promote an increase in critical thought and the degree of multicultural attitude change, tolerance for ambiguity inhibits critical thinking and, ultimately multicultural attitude change. As expected, those students showing the least amount of decrease (or even an increase) in intolerance across the semester, earned lower grades in the course than those students who showed a significant decrease in intolerance, t(1,19) = 4.659, p < .001. Students who demonstrated the most change in their Tolerance for Ambiguity (showed an increasing ability to tolerate ambiguity) earned the highest grades in the course. This is, especially, significant because faculty did not know student scores on this measure until after all assignments had been graded and course grades assigned. An assignment designed to assist students in making their assumption and inferences processes visible so they could be explored, was implemented with the goal of this exploration then promoting more tolerance for ambiguity, which, as already outlined, promotes critical thought. The assignment offers students two options and then requires them to explore what they have learned about inferences and/or assumptions This presentation outlines the assignment and demonstrates the humanities model, what students learn from particular assignments and how it fosters a change in Tolerance for Ambiguity which, serves as the foundational component of critical thinking.

Keywords: critical thinking, humanities education, sociocentrism, tolerance for ambiguity

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Authors: Yun Chan Lee

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Background: End-of-life care is a large area of all nursing practice and student nurses are likely to meet dying patients in many placement areas. It is therefore important to understand the emotional responses and coping strategies of student nurses in order for nursing education systems to have some appreciation of how nursing students might be supported in the future. Methodology: This research used a qualitative phenomenological approach. Six student nurses understanding a degree-level adult nursing course were interviewed. Their responses to questions were analyzed using interpretative phenomenological analysis. Finding: The findings identified 3 main themes. First, the common experience of ‘unpreparedness’. A very small number of participants felt that this was unavoidable and that ‘no preparation is possible’, the majority felt that they were unprepared because of ‘insufficient input’ from the university and as a result of wider ‘social taboos’ around death and dying. The second theme showed that emotions were affected by ‘the personal connection to the patient’ and the important sub-themes of ‘the evoking of memories’, ‘involvement in care’ and ‘sense of responsibility’. The third theme, the coping strategies used by students, seemed to fall into two broad areas those ‘internal’ with the student and those ‘external’. In terms of the internal coping strategies, ‘detachment’, ‘faith’, ‘rationalization’ and ‘reflective skills’ are the important components of this part. Regarding the external coping strategies, ‘clinical staff’ and ‘the importance of family and friends’ are the importance of accessing external forms of support. Implication: It is clear that student nurses are affected emotionally by caring for dying patients and many of them have apprehension even before they begin on their placements but very often this is unspoken. Those anxieties before the placement become more pronounced during and continue after the placements. This has implications for when support is offered and possibly its duration. Another significant point of the study is that participants often highlighted their wish to speak to qualified nurses after their experiences of being involved in end-of-life care and especially when they had been present at the time of death. Many of the students spoke that qualified nurses were not available to them. This seemed to be due to a number of reasons. Because the qualified nurses were not available, students had to make use of family members and friends to talk to. Consequently, the implication of this study is not only to educate student nurses but also to educate the qualified mentors on the importance of providing emotional support to students.

Keywords: nursing students, coping strategies, end-of-life care, emotional responses

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Authors: Hafiz Gulfam Ahmad, Chuangdong Li, Zeeshan Ahmad

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In this paper, we proposed a parallel IDS and honeypot based approach to detect and analyze the unknown and known attack taxonomy for improving the IDS performance and protecting the network from intruders. The main theme of our approach is to record and analyze the intruder activities by using both the low and high interaction honeypots. Our architecture aims to achieve the required goals by combing signature based IDS, honeypots and generate the new signatures. The paper describes the basic component, design and implementation of this approach and also demonstrates the effectiveness of this approach reducing the probability of network attacks.

Keywords: network security, intrusion detection, honeypot, snort, nmap

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Authors: Seval Kula-Kartal

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Developing students’ reading comprehension skills is an aim that is difficult to accomplish and requires to follow long-term and systematic teaching and assessment processes. In these processes, teachers need tools to provide guidance to them on what reading comprehension is and which comprehension skills they should develop. Due to a lack of clear and evidence-based frameworks defining reading comprehension skills, especially in Turkiye, teachers and students mostly follow various processes in the classrooms without having an idea about what their comprehension goals are and what those goals mean. Since teachers and students do not have a clear view of comprehension targets, strengths, and weaknesses in students’ comprehension skills, the formative feedback processes cannot be managed in an effective way. It is believed that detecting and defining influential comprehension skills may provide guidance both to teachers and students during the feedback process. Therefore, in the current study, some of the reading comprehension frameworks that define comprehension skills operationally were examined. The aim of the study is to develop a simple and clear framework that can be used by teachers and students during their teaching, learning, assessment, and feedback processes. The current study is qualitative research in which documents related to reading comprehension skills were analyzed. Therefore, the study group consisted of recourses and frameworks which made big contributions to theoretical and operational definitions of reading comprehension. A content analysis was conducted on the resources included in the study group. To determine the validity of the themes and sub-categories revealed as the result of content analysis, three educational assessment experts were asked to examine the content analysis results. The Fleiss’ Cappa coefficient revealed that there is consistency among themes and categories defined by three different experts. The content analysis of the reading comprehension frameworks revealed that comprehension skills could be examined under four different themes. The first and second themes focus on understanding information given explicitly or implicitly within a text. The third theme includes skills used by the readers to make connections between their personal knowledge and the information given in the text. Lastly, the fourth theme focus on skills used by readers to examine the text with a critical view. The results suggested that fundamental reading comprehension skills can be examined under four themes. Teachers are recommended to use these themes in their reading comprehension teaching and assessment processes. Acknowledgment: This research is supported by Pamukkale University Scientific Research Unit within the project, whose title is Developing A Reading Comprehension Rubric.

Keywords: reading comprehension, assessing reading comprehension, comprehension taxonomies, educational assessment

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Authors: Mahin Pourmorad Naseri

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Myths have been an inseparable aspect of man’s life in all nations and cultures across the world over time; however, it seems that the form and use of myths in the poetry of the 20th century have gained a new meaning and purpose. Among the poets of the time, T. S. Eliot in English and Mahdi Akhavan Sales in Persian are the two mostly referred to in this regard. In this paper, the pattern of heroic journey as the main theme in the poetry of Akhavan and Eliot will be reviewed, compared, and contrasted. Attempts have been made to find out how the myth of the hero’s journey has been reflected in the century’s well-known poetry and if myth allusions in these poems confirm or reject Campbell’s claim that mythology can be an appropriate psychological cure for man’s loneliness in today’s life. T. S. Eliot (1888-1965), the English poet, essayist, playwright, publisher, and critic, is mostly known for his modernist poetry and the extensive allusions to mythologies and world literary masterpieces. At the same time, Mahdi Akhavan Sales (1929-1990) Iranian poet, one of the pioneers of modern Persian poetry, is also most well-known for his epic poetic style (Khorasani Style) and also his high amount of allusions to myths, especially Zoroastrian mythology, and his myth-making technique. Although their greatly different cultural background may cause the similarities in their poetic style and themes not to attract attention, at first sight, reading the poems closely through the light of the 20th century’s life context and literary movements reveal interesting similarities in the way they understand and apply myth in their poetry. The present paper reviews the theme of the hero’s journey in Akhavan’s Chavooshi and Eliot’s “Journey of the Magi” from the perspective of Campbell’s notion of mono-myth or the pattern of mythic hero’s journey. The poems will be reviewed in search of the steps of the inward journey the heroes make, the goals they pursue, and how successful they are in achieving the goals. The findings of the study reveal that while the difference in the social context of the poets makes the small differences in the stages of the journey, both journeys end in a gloomy atmosphere for the disappointedly isolated hero who is finally left alone in the godless and materialistic world of 20th century. It is also evident that both poets meant to fulfill their responsibility of reviving mythology in writing the poems.

Keywords: myth, Akhavan, Eliot, poetry, hero's journey

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Maria Tsouroufli, Andrea Mondokova, Subashini Suresh

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Background: The under-representation of women and consequent failure to fulfil their potential contribution to Science, Technology, Engineering, Maths, and Medicine (STEMM) subjects in the UK is an issue that the Higher Education sector is being encouraged to address. Focus: The aim of this research is to investigate the barriers, facilitators, and incentives that influence diverse groups of women who have embarked upon a related career in STEMM subjects. The project will address a number of interconnected research questions: 1. How do participants perceive the barriers, facilitators and incentives for women in terms of research, teaching and management/leadership at each stage of their development towards forging a career in STEMM? 2. How might gender intersect with ethnicity, pregnancy/maternity and academic grade in the career experiences of women in STEMM? 3. How do participants perceive the example of female role models in emulating them as a career model? 4. How do successful females in STEMM see themselves as role models and what strategies do they employ to promote their careers? 5. How does institutional culture manifest itself as a barrier or facilitator for women in STEMM subjects in the institution? Methodology and Theoretical framework: A mixed-methodology will be employed in a case study of one university. The study will draw on extant quantitative data for context and involve conducting a qualitative inquiry to discover the perceptions of staff and students around the key concepts under study (career progression, sense of belonging and tenure, role-models, personal satisfaction, perceived gender in/equality, institutional culture). The analysis will be informed by an intersectionality framework, feminist and gender theory, and organisational psychology and human resource management perspectives. Implications: Preliminary findings will be collected in 2017. Conclusions will be drawn and used to inform recruitment and retention, and the development and implementation of initiatives to enhance the experiences and outcomes of women working and studying in STEMM subjects in Higher Education.

Keywords: under-representation, women, STEMM subjects, intersectionality

Procedia PDF Downloads 261

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: R. L. Ujjwal, Abhishek Jain

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In the field of computer vision, most facial variations such as identity, expression, emotions and gender have been extensively studied. Automatic age estimation has been rarely explored. With age progression of a human, the features of the face changes. This paper is providing a new comparable study of different type of algorithm to feature extraction [Hybrid features using HAAR cascade & HOG features] & classification [KNN & SVM] training dataset. By using these algorithms we are trying to find out one of the best classification algorithms. Same thing we have done on the feature selection part, we extract the feature by using HAAR cascade and HOG. This work will be done in context of age group classification model.

Keywords: computer vision, age group, face detection

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Authors: Helene Jacobson Pettersson, Linda Lill

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Demographic changes and globalization in society provide new opportunities for social work and social work education in Sweden. There has been an ambition to include these aspects into the Swedish social work education. However, the Swedish welfare state standard continued to be as affectionate as invisible starting point in discussions about people’s way of life and social problems. The aim of this study is to explore content given to ethnic relations in social work in the social work education in Sweden. Our standpoint is that the subject can be understood both from individual and structural levels, it changes over time, varies in different steering documents and differs from the perspectives of teachers and students. Our question is what content is given to ethnic relations in social work by the teachers in their strategies and teaching material. The study brings together research in the interface between education science, social work and research of international migration and ethnic relations. The presented narratives are from longer interviews with a total of 17 university teachers who teach in social work program at four different universities in Sweden. The universities have in different ways a curriculum that involves the theme of ethnic relations in social work, and the interviewed teachers are teaching and grading social workers on specific courses related to ethnic relations at undergraduate and graduate levels. Overall assesses these 17 teachers a large number of students during a semester. The questions were concerned on how the teachers handle ethnic relations in education in social work. The particular focus during the interviews has been the teacher's understanding of the documented learning objectives and content of literature and how this has implications for their teaching. What emerges is the teachers' own stories about the educational work and how they relate to the content of teaching, as well as the teaching strategies they use to promote the theme of ethnic relations in social work education. The analysis of this kind of pedagogy is that the teaching ends up at an individual level with a particular focus on the professional encounter with individuals. We can see the shortage of a critical analysis of the construction of social problems. The conclusion is that individual circumstance precedes theoretical perspective on social problems related to migration, transnational relations, globalization and social. This result has problematic implications from the perspective of sustainability in terms of ethnic diversity and integration in society. Thus these aspects have most relevance for social workers’ professional acting in social support and empowerment related activities, in supporting the social status and human rights and equality for immigrants.

Keywords: ethnic relations in Swedish social work education, teaching content, teaching strategies, educating for change, human rights and equality

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Authors: S. Koppikar, P. Kulkarni, D. Ingale , N. Wagh, S. Deshpande, A. Mahajan, A. Harsulkar

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Crucial role of reactive oxygen species (ROS) in the progression Osteoarthritis (OA) pathogenesis has been endorsed several times though its exact mechanism remains unclear. Oxidative stress is known to instigate classical stress factors such as cytokines, chemokines and ROS, which hampers cartilage remodelling process and ultimately results in worsening the disease. Synovial fluid (SF) is a biological communicator between cartilage and synovium that accumulates redox and biochemical signalling mediators. The present work attempts to measure several oxidative stress markers in the synovial fluid obtained from knee OA patients with varying degree of disease severity. Thirty OA and five Meniscal-tear (MT) patients were graded using Kellgren-Lawrence scale and assessed for Nitric oxide (NO), Nitrate-Nitrite (NN), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Potential (FRAP), Catalase (CAT), Superoxide dismutase (SOD) and Malondialdehyde (MDA) levels for comparison. Out of various oxidative markers studied, NO and SOD showed significant difference between moderate and severe OA (p= 0.007 and p= 0.08, respectively), whereas CAT demonstrated significant difference between MT and mild group (p= 0.07). Interestingly, NN revealed statistically positive correlation with OA severity (p= 0.001 and p= 0.003). MDA, a lipid peroxidation by-product was estimated maximum in early OA when compared to MT (p= 0.06). However, FRAP did not show any correlation with OA severity or MT control. NO is an essential bio-regulatory molecule essential for several physiological processes, and inflammatory conditions. However, due to its short life, exact estimation of NO becomes difficult. NO and its measurable stable products are still it is considered as one of the important biomarker of oxidative damage. Levels of NO and nitrite-nitrate in SF of patients with OA indicated its involvement in the disease progression. When SF groups were compared, a significant correlation among moderate, mild and MT groups was established. To summarize, present data illustrated higher levels of NO, SOD, CAT, DPPH and MDA in early OA in comparison with MT, as a control group. NN had emerged as a prognostic bio marker in knee OA patients, which may act as futuristic targets in OA treatment.

Keywords: antioxidant, knee osteoarthritis, oxidative stress, synovial fluid

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Authors: Stuart Bassman

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Services that focus on the synthesis of research and clinical practice are vital in providing efficacious change for the men and women who have been victims of childhood sexual abuse. This study will address what processes have been helpful in being a catalyst in changing one’s inner life as well as providing meaningful applications and fulfilling experiences. Initially, we would focus on the Myths regarding childhood sexual abuse. This would include Grooming behaviors and Delayed Disclosures. Subsequently, we would address the Mess that follows from not recognizing the adverse impairments that result from Childhood Sexual Abuse. Finally, we would conclude by looking at the Mastery that could arise from moving from being a Victim to a Survivor and a Thriver.

Keywords: trauma, childhood, somatic, treatment

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Authors: Badriah Alayidi, Emad Alyahya

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Background: Most people with Multiple Sclerosis (MS) report worsening balance as the condition progresses. Poor balance control is also well known to be a significant risk factor for both falling and fear of falling. The increased risk of falls with disease progression thus makes balance control an essential target of gait rehabilitation amongst people with MS. Intervention programs have developed various methods to improve balance control, and accumulating evidence suggests that exercise programs may help people with MS improve their balance. Among these methods, virtual reality (VR) is growing in popularity as a balance-training technique owing to its potential benefits, including better compliance and greater user happiness. However, it is not clear if a VR environment will induce different balance control mechanisms in MS as compared to healthy individuals or traditional environments. Therefore, this study aims to examine how individuals with MS control their balance in a VR setting. Methodology: The proposed study takes an empirical approach to estimate and determine the role of balance response in persons with MS using a VR environment. It will use primary data collected through patient observations, physiological and biomechanical evaluation of balance, and data analysis. Results: The preliminary systematic review and meta-analysis indicated that there was variability in terms of the outcome assessing balance response in people with MS. The preliminary results of these assessments have the potential to provide essential indicators of the progression of MS and contribute to the individualization of treatment and evaluation of the interventions’ effectiveness. The literature describes patients who have had the opportunity to experiment in VR settings and then used what they have learned in the real world, suggesting that this VR setting could be more appealing than conditional settings. The findings of the proposed study will be beneficial in estimating and determining the effect of VR on balance control in persons with MS. In previous studies, VR was shown to be an interesting approach to neurological rehabilitation, but more data are needed to support this approach in MS. Conclusions: The proposed study enables an assessment of balance and evaluations of a variety of physiological implications related to neural activity as well as biomechanical implications related to movement analysis.

Keywords: multiple sclerosis, virtual reality, postural control, balance

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Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

Procedia PDF Downloads 327

Authors: Sana Fatima, Paul Sadler, Jon Cooper, David Mendel, Ayesha Jameel

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Background: Neurodiversity refers to intrinsic differences between human minds and encompasses dyspraxia, dyslexia, attention deficit hyperactivity disorder, dyscalculia, autism spectrum disorder, and Tourette syndrome. There is increasing recognition of neurodiversity in relation to disability/diversity in medical education and the associated impact on training, career progression, and personal and professional wellbeing. In addition, documented and anecdotal evidence suggests that medical educators and training providers in all four nations (UK) are increasingly concerned about understanding neurodiversity and identifying and providing support for neurodivergent trainees. Summary of Work: A national Neurodiversity Task and Finish group were established to survey Health Education England local office Professional Support teams about insights into infrastructure, training for educators, triggers for assessment, resources, and intervention protocols. This group drew from educational leadership, professional and personal neurodiverse expertise, occupational medicine, employer human resource, and trainees. An online, exploratory survey was conducted to gather insights from supervisors and trainers across England using the Professional Support Units' platform. Summary of Results: This survey highlighted marked heterogeneity in the identification, assessment, and approaches to support and management of neurodivergent trainees and highlighted a 'deficit' approach to neurodiversity. It also demonstrated a paucity of educational and protocol resources for educators and supervisors in supporting neurodivergent trainees. Discussions and Conclusions: In phase one, we focused on faculty development. An educational repository for all supervising trainees using a thematic approach was formalised. This was guided by our survey findings specific for neurodiversity and took a triple 'A' approach: awareness, assessment, and action. This is further supported by video material incorporating stories in training as well as mobile workshops for trainers for more immersive learning. The subtle theme from both the survey and Task and finish group suggested a move away from deficit-focused methods toward a positive holistic, interdisciplinary approach within a biopsychosocial framework. Contributions: 1. Faculty Knowledge and basic understanding of neurodiversity are key to supporting trainees with known or underlying Neurodiverse conditions. This is further complicated by challenges around non-disclosure, varied presentations, stigma, and intersectionality. 2. There is national (and international) inconsistency in the approach to how trainees are managed once a neurodiverse condition is suspected or diagnosed. 3. A carefully constituted and focussed Task and Finish group can rapidly identify national inconsistencies in neurodiversity and implement rapid educational interventions. 4. Nuanced findings from surveys and discussion can reframe the approach to neurodiversity; from a medical model to a more comprehensive, asset-based, biopsychosocial model of support, fostering a cultural shift, accepting 'diversity' in all its manifestations, visible and hidden.

Keywords: neurodiversity, professional support, human considerations, workplace wellbeing

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Irene Ahmed

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This is a research manuscript that lay vehemence upon the brazen reality behind the façade of aestheticism of the society. The journal is a conglomeration of a critical analysis of artistic portrait of The Ophelia and The Last Supper and the literary portrait of W.M.Thackeray’s Vanity Fair singularizing the theme of the paper. The portrait Last Supper highlights the morality of Jesus to be in a possession of a super-human quality of forgiving everybody and to know the foregone destiny. But how is it possible that he is not taking any step to avoid the dismal future despite it is known much earlier? Similarly, how is it possible that Ophelia is drowning and she is not aware of the fact? The answers are found in literary portrait of Vanity Fair, where vanity is given the utmost importance keeping aside all other subjects and my subject of research orbs around it.

Keywords: acrimonious, brazen reality, vanity fair, Ophelia and the Last Supper

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