Search results for: focus marker
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5952

Search results for: focus marker

5322 The Predictive Value of Micro Rna 451 on the Outcome of Imatinib Treatment in Chronic Myeloid Leukemia Patients

Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

Abstract:

Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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5321 Perspectives of charitable organisations on the impact of the COVID-19 pandemic on family carers of people with profound and multiple intellectual disabilities.

Authors: Mark Linden, Trisha Forbes, Michael Brown, Lynne Marsh, Maria Truesdale, Stuart Todd, Nathan Hughes

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Background The COVID-19 pandemic resulted in a reduction of health care services for many family carers of people with profound and multiple intellectual disabilities (PMID). Due to lack of services, family carers turned to charities for support during the pandemic. We explored the views of charity workers across the UK and Ireland who supported family carers during the COVID-19 pandemic and explored their views on effective online support programmes for family carers. Methods This was a qualitative study using online focus groups with participants (n = 24) from five charities across the UK and Ireland. Questions focused on challenges, supports, coping and resources which helped during lockdown restrictions. Focus groups were audio recorded, transcribed verbatim, and analysed through thematic analysis. Findings Four themes were identified (i) ‘mental and emotional health’, (ii) ‘they who shout the loudest’ (fighting for services), (iii) ‘lack of trust in statutory services’ and (iv) ‘creating an online support programme’. Mental and emotional health emerged as the most prominent theme and included three subthemes named as ‘isolation’, ‘fear of COVID-19’ and ‘the exhaustion of caring’. Conclusions The withdrawal of many services during the COVID-19 pandemic further isolated and placed strain on family carers. Even after the end of the pandemic family cares continue to report on the struggle to receive adequate support. There is a critical need to design services, including online support programmes, in partnership with family carers which adequately address their needs.

Keywords: intellectual disability, family carers, COVID-19, charities

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5320 Egyptian and Irish Female Protagonists: A Comparative Study of Al-Hakim's Song of Death and Synge's Riders to the Sea

Authors: Ahmed Mohammed Ghaleb, Ehab Saleh Alnuzaili

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This paper attempts to generally examine Tawfiq Al-Hakim's Song of Death (1950) and John Millington Synge's Riders to the Sea (1904) by comparatively bringing the two plays under focus. Strikingly, the similarities between the two plays appear in the plot, picturization of the characters, tragic intensity, structural perfection, and the economy of language. Plot structure, albeit a simple one in both plays, is enriched by the playwrights' effective use of language, symbols, imagery, and tragic irony. Neither of the two plays has the traditional five-act structure; they are one-act plays. From a feminist point of view, the domination of female characters is observed in both plays. The female protagonists are the main focus of the two plays. Their brave characters and struggle are highly depicted. While Al-Hakim's protagonist is presented as a victim of tribal customs, Synge's protagonist is shown as a victim of nature. Both plays can be described as 'feminine tragedies' using the words of Oona Frwaley. Although the two plays appeared in totally different historical periods of time, both share considerable similarities, thematic as well as linguistic, which result in a concern to investigate them. The paper, basically, aims at asserting the commonalities between human beings and creating awareness of intercultural negotiations and connections. It attempts to bridge the cultural, intellectual, and social gap between Arab and Irish drama by exploring the common elements of the two plays. Thus, the paper presents a critical and comparative study of both plays highlighting the portrayal of the female protagonists.

Keywords: economy of language, imagery, protagonist, symbols, tragic intensity, tragic irony

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5319 The Sense of Recognition of Muslim Women in Western Academia

Authors: Naima Mohammadi

Abstract:

The present paper critically reports on the emergency of Iranian international students in a large public university in Italy. Although the most sizeable diaspora of Iranians dates back to the 1979 revolution, a huge wave of Iranian female students travelled abroad after the Iranian Green Movement (2009) due to the intensification of gender discrimination and Islamization. To explore the experience of Iranian female students at an Italian public university, two complementary methods were adopted: a focus group and individual interviews. Focus groups yield detailed collective conversations and provide researchers with an opportunity to observe the interaction between participants, rather than between participant and researcher, which generates data. Semi-structured interviews allow participants to share their stories in their own words and speak about personal experiences and opinions. Research participants were invited to participate through a public call in a Telegram group of Iranian students. Theoretical and purposive sampling was applied to select participants. All participants were assured that full anonymity would be ensured and they consented to take part in the research. A two-hour focus group was held in English with participants in the presence and some online. They were asked to share their motivations for studying in Italy and talk about their experiences both within and outside the university context. Each of these interviews lasted from 45 to 60 minutes and was mostly carried out online and in Farsi. The focus group consisted of 8 Iranian female post-graduate students. In analyzing the data a blended approach was adopted, with a combination of deductive and inductive coding. According to research findings, although 9/11 was the beginning of the West’s challenges against Muslims, the nuclear threats of Islamic regimes promoted the toughest international sanctions against Iranians as a nation across the world. Accordingly, carrying an Iranian identity contributes to social, political, and economic exclusion. Research findings show that geopolitical factors such as international sanctions and Islamophobia, and a lack of reciprocity in terms of recognition, have created a sense of stigmatization for veiled and unveiled Iranian female students who are the largest groups of ‘non-European Muslim international students’ enrolled in Italian universities. Participants addressed how their nationality has devalued their public image and negatively impacted their self-confidence and self-realization in academia. They highlighted the experience of an unwelcoming atmosphere by different groups of people and institutes, such as receiving marked students’ badges, rejected bank account requests, failed visa processes, secondary security screening selection, and hyper-visibility of veiled students. This study corroborates the need for institutions to pay attention to geopolitical factors and religious diversity in student recruitment and provide support mechanisms and access to basic rights. Accordingly, it is suggested that Higher Education Institutions (HEIs) have a social and moral responsibility towards the discrimination and both social and academic exclusion of Iranian students.

Keywords: Iranian diaspora, female students, recognition theory, inclusive university

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5318 Sexual Behaviors and Its Predictors among Iranian Women in Iran: A Cross-Sectional Study

Authors: Zahra Karimian, Effat Merghati Khoei, Raziyeh Maasoumi

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Background: Women's sexual well-being is center of focus in the field of sexology. Study of sexual behavior and investigating its predictors is important in women's health promotion. Objectives: This study aimed to explore the components of sexual behaviors and their possible associations with the women's demographic. Methods: A National Sexual Behavior Assessment Questionnaire was administered to 500 women ages 15 to 45 who referred to the public health centers seeking for health care services. The associations with demographic were examined. Results: From all participant, 31.8% of women obtain high score in the sexual capacity 21.2% in sexual motivation and 0.2% in sexual function. In sexual script component, 86.2% of women were holding traditional beliefs toward sexual behaviors; the majority (91.5%) of women believed in mutual and relational sexuality, 83.4% believed in androcentricity (male-dominated sexuality). Pearson correlation test showed significant positive correlations between sexual capacity, motivation, function and sexual script (p < 0.05). Regression model showed that sexual capacity is associated with women's education, age of her spouse. Sexual function and sexual motivation were significantly associated with the age of subjects' spouses. Conclusion: In this study, lower score was found in sexual performance while women were scored higher in the sexual capacity and motivation. We argue that these lower score in sexual performance more likely is due to the level of participants' religiosity and formation of their sexuality through an androcentric culture. Women's level of education and the spouse age appear to be predicting factors in the scores the subjects gained. We suggest that gender-specific and culturally sensitive sexuality education should be focus of women's health programs in Iran.

Keywords: sexual behaviors, women, health, Iran

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5317 Mouse Knockouts for Elucidating the Role of Cysteine-Rich Angiogenic Inducer 61 in Tendon Development and Maintenance

Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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5316 Anti-TNF: Possibilities of Rising Anti-Phosphorylcholine Antibodies

Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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5315 An Examination of Economic Evaluation Approaches in Mental Health Promotion Initiatives Targeted at Black and Asian Minority Ethnic Communities in the UK: A Critical Discourse Analysis

Authors: Phillipa Denise Peart

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Black Asian and Minority Ethnic (BAME) people are more at risk of developing mental health disorders because they are more exposed to unfavorable social, economic, and environmental circumstances. These include housing, education, employment, community development, stigma, and discrimination. However, the majority of BAME mental health intervention studies focus on treatment with therapeutically effective drugs and use basic economic methods to evaluate their effectiveness; as a result, little is invested in the economic assessment of psychosocial interventions in BAME mental health. The UK government’s austerity programme and reduced funds for mental health services, has increased the need for the evaluation and assessment of initiatives to focus on value for money. The No Health without Mental Health policy (2011) provides practice guidance to practitioners, but there is little or no mention of the need to provide mental health initiatives targeted at BAME communities that are effective in terms of their impact and the cost-effectiveness. This, therefore, appears to contradict with and is at odds with the wider political discourse, which suggests there should be an increasing focus on health economic evaluation. As a consequence, it could be argued that whilst such policies provide direction to organisations to provide mental health services to the BAME community, by not requesting effective governance, assurance, and evaluation processes, they are merely paying lip service to address these problems and not helping advance knowledge and practice through evidence-based approaches. As a result, BAME communities suffer due to lack of efficient resources that can aid in the recovery process. This research study explores the mental health initiatives targeted at BAME communities, and analyses the techniques used when examining the cost effectiveness of mental health initiatives for BAME mental health communities. Using critical discourse analysis as an approach and method, mental health services will be selected as case studies, and their evaluations will be examined, alongside the political drivers that frame, shape, and direct their work. In doing so, it will analyse what the mental health policies initiatives are, how the initiatives are directed and demonstrate how economic models of evaluation are used in mental health programmes and how the value for money impacts and outcomes are articulated by mental health programme staff. It is anticipated that this study will further our understanding in order to provide adequate mental health resources and will deliver creative, supportive research to ensure evaluation is effective for the government to provide and maintain high quality and efficient mental health initiatives targeted at BAME communities.

Keywords: black, Asian and ethnic minority, economic models, mental health, health policy

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5314 The Issue of Pedagogical Approaches in Higher Education: Public Universities as an Example

Authors: Majda El Moufarej

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Higher education plays a central role in socio-economic development. However, with the wave of change mainly due to the extensive use of technology in the workplace, the rate of unemployment among graduates rises because they lack the appropriate competencies and skills currently required in professional life. This situation has led higher education institutions worldwide to reconsider their missions, strategic planning, and curricula, among other elements to redress the image of the university as expected. When it comes to practice, there are many obstacles that hinder the achievement of the expected objectives, especially in public universities with free access, as in the case of Morocco. Nevertheless, huge efforts have been made by educational managers to improve the quality of education by focusing on the issue of pedagogical approaches, where university teachers assume more responsibility to save the situation. In this paper, the focus will be placed on the issue of pedagogical approaches to be adopted, depending on the nature of the subject, the size of the class, the available equipment, the students’ level and degree of motivation. Before elaborating on this idea, it may be more insightful to begin by addressing another variable, which concerns the new role of university teachers and their qualification in pedagogical competence. Then, the discussion will revolve around five pedagogical approaches currently adopted in western universities and the focus will be exclusively placed on the one which is called “the Systematic Approach to course Design”, due to its crucial relevance in the teaching of subjects in the schools of humanities, as it can guide the teacher in the development of an explicit program for purposeful teaching and learning. The study is based on a qualitative method, and the findings will be analyzed and followed by some recommendations about how to overcome difficulties in teaching large groups, while transmitting the relevant knowledge and skills on demand in the workplace.

Keywords: higher education, public universities, pedagogical approaches, pedagogical competence

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5313 The Effects of Evidence-Based Nursing Training and Consultation Program on Self-Efficacy and Outcome Expectancy of Evidence-Based Practice among Nurses

Authors: Yea-Pyng Lin

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Evidence-based nursing (EBN) can improve quality of patient care and reduce medical expenses. Development of training and consultation program according to nurses’ needs and difficulties is essential to promote their competence and self-efficacy in EBN. However, limited research evaluated the effects of EBN program on EBN self-efficacy among nurses. This study aimed to evaluate the effects of an EBN consultation program on self-efficacy and outcome expectancy of evidence-based practice (EBP) among nurses. A two-group pretest-posttest quasi-experimental design was used. A purposive sample of full-time nurses was recruited from a hospital. Experimental group (n=28) received the EBN consultation program including 18-hour EBN training courses, hand-on practices and group discussion by faculty mentors. Control group (n=33) received regular in-service education with no EBN program. All participants received baseline and post-test assessment using Chinese version of Self-Efficacy in EBP scale (SE-EBP) and Outcome Expectancy for EBP scale (OE-EBP). After receiving EBN consultation program, experimental group’s posttest scores of SE-EBP (t=-4.98, p<0.001) and OE-SEP (t=-3.65, p=0.001) were significantly higher than those of the pretests. By controlling the age and years of nursing work experience, the experimental group‘s SE-EBP(F=10.47, p=0.002) and OE-SEP(F=9.53, p=0.003) scores were significantly improved compared to those of the control group. EBN program focus on hand-on practice and group discussion by faculty mentors in addition to EBN training courses can improve EBP self-efficacy and outcome expectancy among nurses. EBN program focus on English literature reading, database searching, and appraisal practice according to nurses’ needs and difficulties can promote implementation of EBN.

Keywords: evidence-based nursing, evidence-based practice, consultation program, self-efficacy, outcome expectancy

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5312 Privatization and Ensuring Accountability in the Provision of Essential Services: A Case of Water in South Africa

Authors: Odufu Ifakachukwu Clifford

Abstract:

Developing country governments are struggling to meet the basic needs and demands of citizens, especially so for the rural poor. With tightly constrained budgets, these governments have followed the lead of developed countries that have sought to restructure public service delivery through privatization, contracting out, public-private partnerships, and similar reforms. Such reforms in service delivery are generally welcomed when it is believed that private sector partners are better equipped to provide certain services than are governments. With respect to basic and essential services, however, a higher degree of uncertainty and apprehension exists as the focus shifts from simply minimizing the costs of delivering services to broadening access to all citizens. The constitution stipulates that everyone has the right to have access to sufficient food and water. Affordable and/or subsidized water, then, is not a privilege but a basic right of all citizens. Citizens elect political representatives to serve in office, with their sole mandate being to provide for the needs of the citizenry. As governments pass on some amount of responsibility for service delivery to private businesses, these governments must be able to exercise control in order to account to the people for the work done by private partners. This paper examines the legislative and policy frameworks as well as the environment within which PPPs take place in South Africa and the extent to which accountability can be strengthened in this environment. Within the aforementioned backdrop of PPPs and accountability, the constricted focus area of the paper aims to assess the extent to which the provision of clean and safe consumable water in South Africa is sustainable, cost-effective in terms of provision, and affordable to all.

Keywords: privatisation, accountability, essential services, government

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5311 A Literature Review about Responsible Third Cycle Supervision

Authors: Johanna Lundqvist

Abstract:

Third cycle supervision is a multifaceted and complex task for supervisors in higher education. It progresses over several years and is affected by several proximal and distal factors. It can result in positive learning outcomes for doctoral students and high-quality publications. However, not all doctoral students thrive during their doctoral studies; nor do they all complete their studies. This is problematic for both the individuals themselves as well as society at large: doctoral students are valuable and important in current research, future research and higher education. The aim of this literature review is to elucidate what responsible third cycle supervision can include and be in practice. The question posed is as follows: according to recent literature, what is it that characterises responsible third cycle supervision in which doctoral students can thrive and develop their research knowledge and skills? A literature review was conducted, and the data gathered from the literature regarding responsible third cycle supervision was analysed by means of a thematic analysis. The analysis was inspired by the notion of responsible inclusion outlined by David Mitchell. In this study, the term literature refers to research articles and regulations. The results (preliminary) show that responsible third cycle supervision is associated with a number of interplaying factors (themes). These are as follows: committed supervisors and doctoral students; a clear vision and research problem; an individual study plan; adequate resources; interaction processes and constructive feedback; creativity; cultural awareness; respect and research ethics; systematic quality work and improvement efforts; focus on overall third cycle learning goals; and focus on research presentations and publications. Thus, responsible third cycle supervision can occur if these factors are realized in practice. This literature review is of relevance to evaluators, researchers, and management in higher education, as well as third cycle supervisors.

Keywords: doctoral student, higher education, third cycle supervisors, third cycle programmes

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5310 Phytochemical Screening and Hepatotoxic Effect of Datura metel Linn. Aqueous Seed Extract in Albino Wistar Rats

Authors: I. M. Fakai, A. Abdulhamid, I. Sani, F. Bello, E. O. Olusesi

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The phytochemical screening and hepatotoxic effect of Datura metel aqueous seeds extract in Albino Wistar rats were evaluated. Phytochemicals were screened using standard methods. The enzymes activity and liver function indices were also determined using standard methods of analysis. The phytochemicals screening revealed the presence of alkaloid, tannin, glycoside and flavonoid. The organ-body weight decreased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The activity of alkaline phosphatase decreased significantly (P<0.05) in the liver and increased significantly in the serum at all the doses of the extract treated groups compared to the control. The activity of serum alanine transaminase increased significantly (P<0.05) while there is no significant difference (P>0.05) in the activity liver alanine transaminase at all the doses of the extract treated groups compared to the control. The result also revealed significant increase (P<0.05) in the aspartate transaminase activity in both liver and serum at all doses of the extract treated groups compared to the control. Serum total protein, albumin, globulin, and total bilirubin concentration decreased significantly (P<0.05), while direct bilirubin concentration increased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The present study therefore revealed that, the present of some phytochemicals in the plant extract attributed the plant to its hepatotoxic effects as revealed in the alteration of marker enzymes and some liver function indices analyzed.

Keywords: datura metel, transaminases, hepatotoxic effect, phytochemicals, rats

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5309 Relationship between Matrilin-3 (MATN-3) Gene Single Nucleotide Six Polymorphism, Transforming Growth Factor Beta 2 and Radiographic Grading in Primary Osteoarthritis

Authors: Heba Esaily, Rawhia Eledl, Daila Aboelela, Rasha Noreldin

Abstract:

Objective: Assess serum level of Transforming growth factor beta 2 (TGF-β2) and Matrilin-3 (MATN3) SNP6 polymorphism in osteoarthritic patients Background: Osteoarthritis (OA) is a musculoskeletal disease characterized by pain and joint stiffness. TGF-β 2 is involved in chondrogenesis and osteogenesis, It has found that MATN3 gene and protein expression was correlated with the extent of tissue damage in OA. Findings suggest that regulation of MATN3 expression is essential for maintenance of the cartilage extracellular matrix microenvironment Subjects and Methods: 72 cases of primary OA (56 with knee OA and 16 with generalized OA were compared with that of 18 healthy controls. Radiographs were scored with the Kellgren-Lawrence scale. Serum TGF-β2 was measured by using (ELISA), levels of marker were correlated to radiographic grading of disease and MATN3 SNP6 polymorphism was determined by (PCR-RFLP). Results: MATN3 SNP6 polymorphism and serum level of TGF-β2 were higher in OA compared with controls. Genotype, NN and N allele frequency were higher in patients with OA compared with controls. NN genotype and N allele frequency were higher in knee osteoarthritis than generalized OA. Significant positive correlation between level of TGFβ2 and radiographic grading in group with knee OA, but no correlation between serum level of TGFβ2 and radiographic grading in generalized OA. Conclusion: MATN3 SNP6 polymorphism and TGF-β2 implicated in the pathogenesis of osteoarthritis. Association of N/N genotype with primary osteoarthritis emphasizes on the need for prospective study include larger sample size to confirm the results of the present study.

Keywords: Matrilin-3, transforming growth factor beta 2, primary osteoarthritis, knee osteoarthritis

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5308 Investigation on Biomass as an Alternate Source for Power Generation

Authors: Narsimhulu Sanke, D. N. Reddy

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The purpose of the paper is to discuss the biomass as a renewable source of energy for power generation. The setup is designed and fabricated in the Centre for Energy Technology (CET) and four different fuels are tested in the laboratory, but here the focus is on wood blocks (fuel) combustion with temperature, gas composition percentage by volume and the heating values.

Keywords: biomass, downdraft gasifier, power generation, renewable energy sources

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5307 Malignant Idiopathic Intracranial Hypertension Revealed a Hidden Primary Spinal Leptomeningeal Medulloblastoma

Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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5306 English Language Competency among the Mathematics Teachers as the Precursor for Performance in Mathematics

Authors: Mirriam M. Moleko, Sekanse A. Ntsala

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Language in mathematics instruction enables the teacher to communicate mathematical knowledge to the learners with precision. It also enables the learner to deal with mathematical activities effectively. This scholarly piece was motivated by the fact that mathematics performance in the South African primary classrooms has not been satisfactory, and English, which is a Language of Learning and Teaching (LoLT) for the majority of the learners, has been singled out as one of the major impediments. This is not only on the part of the learners, but also on the part of the teachers as well. The study thus focused on the lack of competency in English among the primary school teachers as one of the possible causes of poor performance in mathematics in primary classrooms. The qualitative processes, which were premised on the social interaction theory as a lens, sourced the narratives of 10 newly qualified primary school mathematics teachers from the disadvantaged schools on the matter. This was achieved through the use of semi-structured interviews and focus group discussions. The data, which were analyzed thematically, highlighted the actuality that the challenges cut across the pre-service stage to the in-service stage. The findings revealed that the undergraduate mathematics courses in the number of the institutions neglect the importance of language. The study further revealed that the in-service mathematics teachers lack adequate linguistic command, thereby finding it difficult to successfully teach some mathematical concepts, or even to outline instructions clearly. The study thus suggests the need for training institutions to focus on improving the teachers’ English language competency. The need for intensive in-service training targeting the problem areas was also highlighted. The study thus contributes to the body of knowledge by providing suggestions on how the mathematics teachers’ language incompetency can be mitigated.

Keywords: Competency, English language proficiency, language of learning and teaching, primary mathematics teachers

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5305 Measuring the Likeability of Robots among Seniors: A Field Research

Authors: Balaji Viswanathan, Tim Oates

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A number of pilot projects have commenced across the world to use robots for senior care. We aim to measure the likeability of these robots among seniors and help robot designers focus on the features that matter. We built a robot likability score with over 30 parameters and used this to interview 50 seniors in various locations in the United States. This paper presents the results of this field research.

Keywords: HRI, assistive robotics, social robotics, HCI, aging

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5304 Traumatic Osteoarthritis Induces Mechanical Hyperalgesia through IL-1β/TNF-α-Mediated Upregulation of the Sema4D Gene Expression

Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

Abstract:

Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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5303 EU Integratıon Impact over the Real Convergence

Authors: Badoiu Mihaela Catalina

Abstract:

Main focus of COHESION policy was reducing social and economic disparities between member states and regions, sustainable development and equal opportunities. In this perspective, the present study intend to analyze the evolution of the European architecture and its direct impact over the real convergence in the member states.

Keywords: cooperation, European union, member states, cohesion policy

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5302 Differential Expression of Biomarkers in Cancer Stem Cells and Side Populations in Breast Cancer Cell Lines

Authors: Dipali Dhawan

Abstract:

Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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5301 Utility of CK7, CK20 and CDX-2 as a Potential Panel in Differentiating Primary Ovarian Surface Epithelial Tumors from Metastatic Adenocarcinoma to the Ovary

Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

Abstract:

Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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5300 Nanoparticles Activated Inflammasome Lead to Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

Abstract:

Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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5299 Experiences of Family Carers of People Intellectual Disabilities During the COVID-19 Pandemic

Authors: Mark Linden, Michael Brown, Lynne Marsh, Maria Truesdale, Stuart Todd, Nathan Hughes, Trisha Forbes, Rachel Leonard

Abstract:

Background: The COVID-19 pandemic exacerbated the already significant strain placed on family carers of people with profound and multiple intellectual disabilities (PMID), given the withdrawal of many services during lockdown. The aim of this study was to explore the experiences of family carers of people with PMID during the COVID-19 pandemic. Methods: Online focus groups were conducted with family carers (n=126) from across the UK and the Republic of Ireland. Participants were asked about their experiences of the COVID-19 pandemic, coping strategies, and challenges faced. Focus groups were audio recorded, transcribed verbatim and analyzed through thematic analysis. Findings: Three themes emerged from our analysis of the data: (i) COVID-19 as a double-edged sword, (ii) The struggle for support (iii) the Constant nature of caring. These included 11 subthemes: (i) ‘COVID-19 as a catalyst for change’, ‘Challenges during COVID-19: dealing with change’, ‘Challenges during COVID-19: fear of COVID-19’, ‘The online environment: the new normal’ (ii) ‘Invisibility of male carers’, ‘Carers supporting carers’, ‘The only service you get is lip service: non-existent services’, ‘Knowing your rights’ (iii) ‘Emotional response to the caring role: Feeling devalued’, ‘Emotional response to the caring role: Desperation of caring’, ‘Multiple demands of the caring role.’ Conclusions: Poor or inconsistent access to services and support has been an ongoing difficulty for many family carers. The COVID-19 pandemic has only further intensified these difficulties, increasing family carers' stress. There is an urgent need to design services, such as online support programs, in partnership with family carers that adequately address their needs.

Keywords: intellectual disabilities, family carer, COVID-19, disability

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5298 Detection of MspI Polymorphism and SNP of GH Gene in Some Camel Breeds Reared in Egypt

Authors: Sekena H. Abd El-Aziem, Heba A. M. Abd El-Kader, Sally S. Alam, Othman E. Othman

Abstract:

Growth hormone (GH) is an anabolic hormone synthesized and secreted by the somatotroph cells of the anterior lobe of the pituitary gland in a circadian and pulsatile manner, the pattern of which plays an important role in postnatal longitudinal growth and development, tissue growth, lactation, reproduction as well as protein, lipid and carbohydrate metabolism. The aim of this study was to detect the genetic polymorphism of GH gene in five camel breeds reared in Egypt; Sudany, Somali, Mowaled, Maghrabi and Falahy, using PCR-RFLP technique. Also this work aimed to identify the single nucleotide polymorphism between different genotypes detected in these camel breeds. The amplified fragment of camel GH at 613-bp was digested with the restriction enzyme MspI and the result revealed the presence of three different genotypes; CC, CT and TT in tested breeds and significant differences were recorded in the genotype frequencies between these camel breeds. The result showed that the Maghrabi breed that is classified as a dual purpose camels had higher frequency for allele C (0.75) than those in the other tested four breeds. The sequence analysis declared the presence of a SNP (C→T) at position 264 in the amplified fragment which is responsible for the destruction of the restriction site C^CGG and consequently the appearance of two different alleles C and T. The nucleotide sequences of camel GH alleles T and C were submitted to nucleotide sequences database NCBI/Bankit/GenBank and have accession numbers: KP143517 and KP143518, respectively. It is concluded that only one SNP C→T was detected in GH gene among the five tested camel breeds reared in Egypt and this nucleotide substitution can be used as a marker for the genetic biodiversity between camel breeds reared in Egypt. Also, due to the possible association between allele C and higher growth rate, we can used it in MAS for camels and enter the camels possess this allele in breeding program as a way for enhancement of growth trait in camel breeds reared in Egypt.

Keywords: camel breeds in Egypt, GH, PCR-RFLP, SNPs

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5297 Effect of Hormones Priming on Enzyme Activity and Lipid Peroxidation in Wheat Seed under Accelerated Aging

Authors: Amin Abbasi, Fariborz Shekari, Seyed Bahman Mousavi

Abstract:

Seed aging during storage is a complex biochemical and physiological processes that can lead to reduce seed germination. This phenomenon associated with increasing of total antioxidant activity during aging. To study the effects of hormones on seed aging, aged wheat seeds (control, 90 and 80% viabilities) were treated with GA3, Salicylic Acid, and paclobutrazol and antioxidant system were investigated as molecular biomarkers for seed vigor. The results showed that, seed priming treatment significantly affected germination percentage, normality seedling percentage, H2O2, MDA, CAT, APX, and GPX activates. Maximum germination percentage achieve in GA3 priming in control treatment. Germination percentage and normal seedling percentage increased in other GA3 priming treatment compared with other hormones. Also aging increased MDA, H2O2 content. MDA is considered sensitive marker commonly used for assessing membrane lipid peroxidation and H2O2result in toxicity to cellular membrane system and damages to plant cells. Amount of H2O2 and MDA declined in GA3 treatment. CAT, GPX and APX activities were reduced by increasing the aging time and at different levels of priming. The highest APX activity was observed in Salicylic Acid control treatment and the highest GPX and CAT activity was obtained in GA3 control treatment. The lowest MDA and H2O2 showed in GA3 control treatment, too. Hormone priming increased Antioxidant enzyme activity and decreased amount of reactive oxygen space and malondialdehyde (MDA) under aging treatment. Also, GA3 priming treatments have a significant effect on germination percentage and number of normal seedling. Generally aging seed, increase ROS and lipid peroxidation. Antioxidant enzymes activity of aged seeds increased after hormone priming.

Keywords: hormones priming, wheat, aging seed, antioxidant, lipid peroxidation

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5296 Insulin Resistance in Patients with Chronic Hepatitis C Virus Infection: Upper Egypt Experience

Authors: Ali Kassem

Abstract:

Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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5295 Eosinopenia: Marker for Early Diagnosis of Enteric Fever

Authors: Swati Kapoor, Rajeev Upreti, Monica Mahajan, Abhaya Indrayan, Dinesh Srivastava

Abstract:

Enteric Fever is caused by gram negative bacilli Salmonella typhi and paratyphi. It is associated with high morbidity and mortality worldwide. Timely initiation of treatment is a crucial step for prevention of any complications. Cultures of body fluids are diagnostic, but not always conclusive or practically feasible in most centers. Moreover, the results of cultures delay the treatment initiation. Serological tests lack diagnostic value. The blood counts can offer a promising option in diagnosis. A retrospective study to find out the relevance of leucopenia and eosinopenia was conducted on 203 culture proven enteric fever patients and 159 culture proven non-enteric fever patients in a tertiary care hospital in New Delhi. The patient details were retrieved from the electronic medical records section of the hospital. Absolute eosinopenia was considered as absolute eosinophil count (AEC) of less than 40/mm³ (normal level: 40-400/mm³) using LH-750 Beckman Coulter Automated machine. Leucopoenia was defined as total leucocyte count (TLC) of less than 4 X 10⁹/l. Blood cultures were done using BacT/ALERT FA plus automated blood culture system before first antibiotic dose was given. Case and control groups were compared using Pearson Chi square test. It was observed that absolute eosinophil count (AEC) of 0-19/mm³ was a significant finding (p < 0.001) in enteric fever patients, whereas leucopenia was not a significant finding (p=0.096). Using Receiving Operating Characteristic (ROC) curves, it was observed that patients with both AEC < 14/mm³ and TCL < 8 x 10⁹/l had 95.6% chance of being diagnosed as enteric fever and only 4.4% chance of being diagnosed as non-enteric fever. This result was highly significant with p < 0.001. This is a very useful association of AEC and TLC found in enteric fever patients of this study which can be used for the early initiation of treatment in clinically suspected enteric fever patients.

Keywords: absolute eosinopenia, absolute eosinophil count, enteric fever, leucopenia, total leucocyte count

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5294 Recent Developments in the Application of Deep Learning to Stock Market Prediction

Authors: Shraddha Jain Sharma, Ratnalata Gupta

Abstract:

Predicting stock movements in the financial market is both difficult and rewarding. Analysts and academics are increasingly using advanced approaches such as machine learning techniques to anticipate stock price patterns, thanks to the expanding capacity of computing and the recent advent of graphics processing units and tensor processing units. Stock market prediction is a type of time series prediction that is incredibly difficult to do since stock prices are influenced by a variety of financial, socioeconomic, and political factors. Furthermore, even minor mistakes in stock market price forecasts can result in significant losses for companies that employ the findings of stock market price prediction for financial analysis and investment. Soft computing techniques are increasingly being employed for stock market prediction due to their better accuracy than traditional statistical methodologies. The proposed research looks at the need for soft computing techniques in stock market prediction, the numerous soft computing approaches that are important to the field, past work in the area with their prominent features, and the significant problems or issue domain that the area involves. For constructing a predictive model, the major focus is on neural networks and fuzzy logic. The stock market is extremely unpredictable, and it is unquestionably tough to correctly predict based on certain characteristics. This study provides a complete overview of the numerous strategies investigated for high accuracy prediction, with a focus on the most important characteristics.

Keywords: stock market prediction, artificial intelligence, artificial neural networks, fuzzy logic, accuracy, deep learning, machine learning, stock price, trading volume

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5293 Determination of the Phosphate Activated Glutaminase Localization in the Astrocyte Mitochondria Using Kinetic Approach

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

Abstract:

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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