Search results for: theme progression

Authors: Miao Zhang, Limin Liu, Feng Zhi, Panpan Niu, Mengya Yang, Xuemei Zhu, Ying Diao, Jun Wang, Ying Zhao

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Background and Aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p=0.0043) and advanced (1.8-fold, p=0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ~0.74-fold, p=0.0002(early)/0.0016(advanced); SMC: ~1.55-fold, p=0.0003(early) /0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p=0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.

Keywords: atherosclerosis, phenotype switch of smooth muscle cells, SSAO/VAP-1, semicarbazide

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

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Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Richard O’Riordan, Saritha Unnikrishnan

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Autonomous Vehicles (AVs) are incorporating an increasing number of ADAS features, including automated lane-keeping systems. In recent years, many research papers into lane detection algorithms have been published, varying from computer vision techniques to deep learning methods. The transition from lower levels of autonomy defined in the SAE framework and the progression to higher autonomy levels requires increasingly complex models and algorithms that must be highly reliable in their operation and functionality capacities. Furthermore, these algorithms have no room for error when operating at high levels of autonomy. Although the current research details existing computer vision and deep learning algorithms and their methodologies and individual results, the research also details challenges faced by the algorithms and the resources needed to operate, along with shortcomings experienced during their detection of lanes in certain weather and lighting conditions. This paper will explore these shortcomings and attempt to implement a lane detection algorithm that could be used to achieve improvements in AV lane detection systems. This paper uses a pre-trained LaneNet model to detect lane or non-lane pixels using binary segmentation as the base detection method using an existing dataset BDD100k followed by a custom dataset generated locally. The selected roads will be modern well-laid roads with up-to-date infrastructure and lane markings, while the second road network will be an older road with infrastructure and lane markings reflecting the road network's age. The performance of the proposed method will be evaluated on the custom dataset to compare its performance to the BDD100k dataset. In summary, this paper will use Transfer Learning to provide a fast and robust lane detection algorithm that can handle various road conditions and provide accurate lane detection.

Keywords: ADAS, autonomous vehicles, deep learning, LaneNet, lane detection

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Authors: Atiqa Marium

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In 2015, all 193 UN Member countries adopted the 2030 Agenda for Sustainable Development, which is an ambitious 15- year plan to address some of the most pressing issues the world faces. Goal 4 is about Quality Education which highlights the importance of inclusive and quality education for sustainable development. Sustainable Development Goal 10 focuses on reducing inequalities within and among countries. In June 2019, Federal Government in Canada released “Towards Canada’s 2030 Agenda National Strategy”, which was an important step to move the 2030 Agenda forward. In April 2019, the Ontario government announced the performance-based funding model for publically assisted colleges and universities in Ontario, which is now part of the universities’ budget 2024-2025. The literature review has shown that the funding model has been implemented by different governments to achieve objectives. However, this model has also resulted in conflicting consequences like reducing university autonomy, education quality/ academic standards, and increased equity concerns. The primary focus of this paper will be to analyze the tensions and coherence between the proposed funding model for education for sustainable development goals and targets set by Canada’s 2030 Agenda National Strategy. Considering that the literature review has provided evidence that the performance-based funding model has resulted in reducing quality of education and increased equity issues in other countries, it will be interesting to see how this proposed funding will align with the SDGs of “Quality Education” and “Reduced Inequalities”. This paper will be well-suited for Volume 4, with the theme of re-visioning institutional impact and sustainability. This paper will underscore the importance of policy coherence between federal and provincial policies for higher education institutions in Ontario for better institutional impact and helping universities in the attainment of goals set in 2030 Agenda towards education for sustainable development.

Keywords: performance-based funding model, education for sustainable development, policy coherence, sustainable development gaols

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Authors: Sherif D. El Wakil, John Rice

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The aim of the current work was to employ the finite element method to model a slab, with a small hole across its width, undergoing plastic plane strain deformation. The computational model had, however, to be validated by comparing its results with those obtained experimentally. Since they were in good agreement, the finite element method can therefore be considered a reliable tool that can help gain better understanding of the mechanism of ductile failure in structural members having stress raisers. The finite element software used was ANSYS, and the PLANE183 element was utilized. It is a higher order 2-D, 8-node or 6-node element with quadratic displacement behavior. A bilinear stress-strain relationship was used to define the material properties, with constants similar to those of the material used in the experimental study. The model was run for several tensile loads in order to observe the progression of the plastic deformation region, and the stress concentration factor was determined in each case. The experimental study involved employing the visioplasticity technique, where a circular mesh (each circle was 0.5 mm in diameter, with 0.05 mm line thickness) was initially printed on the side of an aluminum slab having a small hole across its width. Tensile loading was then applied to produce a small increment of plastic deformation. Circles in the plastic region became ellipses, where the directions of the principal strains and stresses coincided with the major and minor axes of the ellipses. Next, we were able to determine the directions of the maximum and minimum shear stresses at the center of each ellipse, and the slip-line field was then constructed. We were then able to determine the stress at any point in the plastic deformation zone, and hence the stress concentration factor. The experimental results were found to be in good agreement with the analytical ones.

Keywords: finite element method to model a slab, slab undergoing plastic deformation, stress distribution around a circular hole, visioplasticity

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Authors: Park Eri, Sklad Marcin, Tsirogianni Stavroula

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In a world where there is increasing exchange and movement of populations groups, and interconnectedness, there are plenty of opportunities for mutual cultural enrichment. However, in everyday life, relations among different cultural groups do not go that smoothly often resulting in discrimination, inequalities and violence. The increasing differentiation of roles, values and worldviews raise a lot of tensions and dilemmas for the state and people -especially in western liberal societies- about issues of acceptance, fairness, justice, autonomy, plurality, freedom, equality and cohesion. Cultural diversity requires a deeper understanding of the roots, meaning and consequences of group differences. We argue, that a psychology from the standpoint of the subject needs to be developed further according to new societal needs. This means within a globalised society, issues regarding the construction of the other as another have become of utmost importance. In constructing the other human beings construct their ideal and possible worlds and meanings about their lives and their significance by drawing on a set of cultural norms, beliefs and values embedded in the different contexts whereby they find themselves in. In this article, we are describing a series of exercises developed in collaboration with University students in the Netherlands that have been piloted with undergraduate 2nd year University Psychology students. These exercises aimed at making tangible and obvious how students apply different moral principles and norms to regulate relationships, which are linked to hegemonic ideological forces. The exercises were in the form of thought experiments that included 8 moral dilemmas, inspired by the moral foundations theory, that touched on different moral principles. The moral dilemmas were built onto each other in incremental steps: from a very tangible/hands-on level to more challenging and demanding ones which require to step into pre-existing networks on knowledge and discourses. After the execution of every dilemma, a discussion followed, which is focused on building links between the ‘theme of the exercise’ and participants’ own lives experiences. In this paper, we provide an evaluation of the methodology used through a discursive analysis of the discussion between the students and the teacher.

Keywords: citizenship, moral dilemmas, social justice, education

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Authors: Amenador Kate Benedicta, Wang Zhiwei

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Since the later parts of the 20th century, the notion of equivalence continues to be a central and critical concept in the development of translation theory. After decades of arguments over word-for-word and free translations methods, scholars attempting to develop more systematic and efficient translation theories began to focus on fundamental translation concepts such as equivalence. Although the concept of equivalence has piqued the interest of many scholars, its definition, scope, and applicability have sparked contentious arguments within the discipline. As a result, several distinct theories and explanations on the concept of equivalence have been put forward over the last half-century. Thus, this study explores and discusses the evolution of the critical concept of equivalence in translation studies through a bibliometric method of investigation of manual and digital books and articles by analyzing different scholars' key contributions and limitations on equivalence from various theoretical perspectives. While analyzing them, emphasis is placed on the innovations that each theory has brought to the comprehension of equivalence. In order to achieve the aim of the study, the article began by discussing the contributions of linguistically motivated theories to the notion of equivalence in translation, followed by functionalist-oriented contributions, before moving on to more recent advancements in translation studies on the concept. Because equivalence is such a broad notion, it is impossible to discuss each researcher in depth. As a result, the most well-known names and their equivalent theories are compared and contrasted in this research. The study emphasizes the developmental progression in our comprehension of the equivalence concept and equivalent effect. It concluded that the various theoretical perspective's contributions to the notion of equivalence rather complement and make up for the limitations of each other. The study also highlighted how troublesome the equivalent concept might become in terms of identifying the nature of translation and how central and unavoidable the concept is in every translation action, despite its limitations. The significance of the study lies in its synthesis of the different contributions and limitations of the various theories offered by scholars on the notion of equivalence, lending literature to both student and scholars in the field, and providing insight on future theoretical development

Keywords: equivalence, functionalist translation theories, linguistic translation approaches, translation theories, Skopos

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Tadesse Melaku Abegaz

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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: Javad Sarvestan, Zdenek Svoboda

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Force-time (F-T) curvature characteristics are globally referenced as the main indicators of athletic jump performance. Nevertheless, to the best of authors’ knowledge, no investigation tried to deeply study the relationship between F-T curve variables and real-game jump performance among elite volleyball players. To this end, this study was designated to investigate the association between F-T curve variables, including movement timings, force, velocity, power, rate of force development (RFD), modified reactive strength index (RSImod), and net impulse with spike jump height during real-game circumstances. Twelve young elite volleyball players performed 3 countermovement jump (CMJ) and 3 spike jump in real-game circumstances with 1-minute rest intervals to prevent fatigue. Shapiro-Wilk statistical test illustrated the normality of data distribution, and Pearson’s product correlation test portrayed a significant correlation between CMJ height and peak RFD (0.85), average RFD (r=0.81), RSImod (r=0.88) and concentric net impulse (r=0.98), and also significant correlation between spike jump height and peak RFD (0.73), average RFD (r=0.80), RSImod (r=0.62) and concentric net impulse (r=0.71). Multiple regression analysis also reported that these factors have a strong contribution in predicting of CMJ (98%) and spike jump (77%) heights. Outcomes of this study confirm that the RFD, concentric net impulse, and RSImod values could precisely monitor and track the volleyball attackers’ explosive strength, muscular stretch-shortening cycle function efficiency, and ultimate spike jump height. To this effect, volleyball coaches and trainers are advised to have an in-depth focus on their athletes’ progression or the impacts of strength trainings by observing and chasing the F-T curve variables such as RFD, net impulse, and RSImod.

Keywords: net impulse, reactive strength index, rate of force development, stretch-shortening cycle

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Authors: Alonge Isaac Olusola

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This paper focuses on the evolution and development of Yoruba theatre during the pre-colonial, colonial and post-colonial years and how Yoruba crime films have been influenced by foreign culture. It emphasizes on the transition of theatre from the ground to the stage and from the stage to the screen with emphasis on the contribution of late Chief Hubert Ogunde who is regarded as the doyen of Yoruba and the entire Nigerian theatre. Using the Theory of Post-colonialism, two modern Yoruba crime films are carefully selected from the numerous available ones to highlight and explain the various aspects of Yoruba films that have been greatly influenced by the foreign cultural practices. The questions to be answered here include 'Which attitudes or cultural practices are widely believed to be that of Yoruba?', 'To what extent are they projected in the selected Yoruba crime films?', 'Which attitudes or cultural practices are widely believed to be foreign among the Yoruba people?', 'To what extent are they projected in the selected Yoruba crime films?'. Although, the British colonial masters granted political independence to Nigeria on October 1, 1960, but a seed of multi-culture and counterculture had been sown into the lives of the Yoruba people. Under the literature review, there is an intensive illumination on some scholars’ ideas and views on what constitutes Yoruba culture, the evolution and development of drama, theatre and films in the Yoruba society and the nature of criminals and criminalities in the Yoruba society and the western world in the pre-colonial and post-colonial times. Furthermore, the processes of interaction between man, his values and his thoughts are also highlighted – a situation that procreates criminal or benevolent acts. Consequently, the paper dwells on how colonialism, despite its so-called merits put the gradual process of urbanization and civilization among the originally rustic, cohesive and moralistic Yoruba society on a supersonic speed that culminated in acquisition of attitudes that are alien to the Yoruba culture. Since a drama is nothing but the theatrical replication of what occurs in the real life, the paper then focuses on the submission that Yoruba crime films have experienced a serious foreign influence in form and content as a result of this encounter. In conclusion, the findings of the impact of foreign cultural practices on Yoruba crime films are highlighted and expatiated with a view to recommending a few steps that could be taken to retain the projection of the original Yoruba cultural practices in Yoruba films, especially the ones that have crime as a theme.

Keywords: culture, films, theatre, Yoruba

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Authors: Simmi Chopra

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In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

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Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: Martin Dupuy, Solange Grunenwald, Pierre-Louis Colombo, Laurence Mahieu, Pomone Richard, Philippe Bartoli

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Endonasal endoscopic trans-sphenoidal surgery for pituitary tumours has become a mainstay of treatment over the last two decades. Although it is generally accepted that there is no significant difference between endoscopic versus microscopic approach for surgical outcomes (endocrine and ophthalmologic status), nasal morbidity seems to the benefit of endoscopic procedures. Minimally invasive endoscopic surgery needs an operative learning curve to achieve surgeon’s efficiency. This learning curve is now well known for surgical outcomes and complications rate, however, few data are available for nasal morbidity. The aim of our series is to document operative experience and nasal quality of life after (NQOL) endoscopic trans-sphenoidal surgery. The prospective pituitary surgical cohort consisted of 525 consecutives patients referred to our Skull Base Diseases Department. Endoscopic procedures were performed by a single neurosurgeon using an uninostril approach. NQOL was evaluated using the Sino-Nasal Test (SNOT-22), the Anterior Base Nasal Inventory (ASBNI) and the Skull Base Inventory Score (SBIS). Data were collected before surgery during hospital stay and 3 months after the surgery. The seventy first patients were compared to the latest 70 patients. There was no significant difference between comparison score before versus after surgery for SNOT-22, ASBNI and SBIS during the single surgeon’s learning curve. Our series demonstrates that in our institution there is no statistically significant learning curve for NQOL after uninostril endoscopic pituitary surgery. A careful progression through sinonasal structures with very limited mucosal incision is associated with minimal morbidity and preserves nasal function. Conservative and minimal invasive approach could be achieved early during learning curve.

Keywords: pituitary surgery, quality of life, minimal invasive surgery, learning curve, pituitary tumours, skull base surgery, endoscopic surgery

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Authors: Michely Vargas Delpupo, José Geraldo Romanello Bueno

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The right to basic sanitation, was elevated to the category of fundamental right by the Brazilian Constitution of 1988 to protect the ecologically balanced environment, ensuring social rights to health and adequate housing warranting dignity of the human person as a principle of the Brazilian Democratic State. Because of their essentiality to the Brazilian population, this article seeks to understand why universal access to basic sanitation is a goal so difficult to achieve in Brazil. Therefore, this research uses the deductive and analytical method. Given the nature of the research literature, research techniques were centered in specialized books on the subject, journals, theses and dissertations, laws, relevant law case and raising social indicators relating to the theme. The relevance of the topic stems, among other things, the fact that sanitation services are essential for a dignified life, i.e. everyone is entitled to the maintenance of the necessary existence conditions are satisfied. However, the effectiveness of this right is undermined in society, since Brazil has huge deficit in sanitation services, denying thus a worthy life to most of the population. Thus, it can be seen that the provision of water and sewage services in Brazil is still characterized by a large imbalance, since the municipalities with lower population index have greater disability in the sanitation service. The truth is that the precariousness of water and sewage services in Brazil is still very concentrated in the North and Northeast regions, limiting the effective implementation of the Law 11.445/2007 in the country. Therefore, there is urgent need for a positive service by the State in the provision of sanitation services in order to prevent and control disease, improve quality of life and productivity of individuals, besides preventing contamination of water resources. More than just social and economic necessity, there is even a an obligation of the government to implement such services. In this sense, given the current scenario, to achieve universal access to basic sanitation imposes many hurdles. These are mainly in the field of properly formulated and implemented public policies, i.e. it requires an excellent institutional organization, management services, strategic planning, social control, in order to provide answers to complex challenges.

Keywords: fundamental rights, health, sanitation, universal access

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Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

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Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

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Authors: Medina Adulyarat

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Like many other countries, Thailand is experiencing an increase in its proportion of older adults. However, the political, social, and religious climates of the various regions of Thailand are very diverse and the life experiences of older Thai citizens can vary greatly by region. For more than a decade, the southernmost provinces, namely Yala, Pattani and Narathiwat, have experienced social and political unrest, often characterized by violence in the form of bombings and shootings, which has impacted the older adults residing in these regions. While, Muslims are considered a minority in Thailand, the majority of individuals in southernmost regions are Muslims, causing these regions to be different in terms of culture and beliefs. Using a phenomenological approach, this study examines older adults’ perceptions of successful aging within the context of violent social and political unrest. This research aims to 1) understand how older adults living in these areas perceive successful aging in relation to Rowe and Kahn’s successful ageing model, and 2) describe the experiences of older adults living in areas of violent social and political unrest. Data were collected using in-depth interviews with eight older adults living in the unrest area, composing of four males and four females aged between 55-75. Content analysis was used to investigate older adults’ perception of successful aging. Older adults living their life amidst the violence did not view the situation as a threat to their life for they viewed that they are not the targets of the unrest situation. Additionally, participants identified their religious beliefs and a strong sense of community belonging as coping strategies employed to deal with social and political unrest. Thus, according to them, the violence did not affect their perception of successful aging. While the participants’ perceptions of successful aging were generally consistent with aspects identified in the successful aging model proposed by Rowe and Kahn, a theme of “financial stability” emerged. The results can be divided into four interrelated themes, which are; 1) engaging with others; 2) religiosity; 3) financial stability; and 4) health. Understanding the older persons’ view of successful aging in vulnerable situations should add more depth and enhance the conceptualization of the successful aging concept.

Keywords: cultural gerontology, minority population, successful aging, unrest situation

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Authors: Ann Devitt, Mairead Brady, Markus Lamest, Stephen Gomez

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This study set out to explore the use of an online collaborative serious game for student learning in a postgraduate introductory marketing module. The simulation game aimed to bridge the theory-practice divide in marketing by allowing students to apply theory in a safe, simulated marketplace. This study addresses the following research questions: Does an online marketing simulation game engage students higher order cognitive skills? Does collaborative activity required develop students’ “soft” skills, such as communication and negotiation? What specific affordances of the online simulation promote learning? This qualitative case study took place in 2014 with 40 postgraduate students on a Business Masters Programme. The two-week intensive module combined lectures with collaborative activity on a marketing simulation game, MMX from Pearsons. The game requires student teams to compete against other teams in a marketplace and design a marketing plan to maximize key performance indicators. The data for this study comprise essays written by students after the module reflecting on their learning on the module. A thematic analysis was conducted of the essays using the following a priori theme sets: 6 levels of the cognitive domain of Blooms taxonomy; 5 principles of Cooperative Learning; affordances of simulation environments including experiential learning; motivation and engagement; goal orientation. Preliminary findings would strongly suggest that the game facilitated students identifying the value of theory in practice, in particular for future employment; enhanced their understanding of group dynamics and their role within that; and impacted very strongly, both positively and negatively on motivation. In particular the game mechanics of MMX, which hinges on the correct identification of a target consumer group, was identified as a key determinant of extrinsic and intrinsic motivation for learners. The findings also suggest that the situation of the simulation game within a broader module which required post-game reflection was valuable in identifying key learning of marketing concepts in both the positive and the negative experiences of the game.

Keywords: simulation, marketing, serious game, cooperative learning, bloom's taxonomy

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Authors: Dusittorn Ngamying

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The research on Thatsana Nataya Chatri Dance: A Creative Conservation Process of Cultural Performing Arts for Competition was aimed at 1) studying the creative conservation process of cultural performing arts; 2) creating conservation process of cultural performing arts of Thatsana Nataya Chatri dance; and 3) utilizing the created performing arts for the competition. The study was conducted using the qualitative research method in the Central region provinces of Thailand through documentary study and data from field observations, interviews and focus group meetings. Data were collected from 50 informants consisting of 10 experts on the subject, 30 practitioners and 10 general information providers. The data collection instruments consisted of participatory and non-participatory forms, structured and non-structured interview schedules and focus group note forms. The data were verified by the triangulation technique and presented using the descriptive analysis. The results of the study reveal that the creative conservation process of cultural performing arts should be initiated by those who have experienced using a prior knowledge in the pursuit of new knowledge. The new knowledge is combined to generate creative work with the conservation process in 9 aspects: acquiring the related knowledge, creating theme and inspiration, designing the music and melody, designing costumes, inventing dance postures, selecting dancers, transferring the dance postures, preparing the stage and performance equipment, planning the performance event. Inventing the conservation process of cultural performing arts Thatsana Nataya Chatri dance consists of 33 dance postures and 14 transformed patterns. The performance requires 6 dancers, 3 males and 3 females. Costume features both male and female classical and modified dancer’s costumes. The duration of the show takes 5 minutes. As for the application for the competition, this creative work has been selected by Dramatic Works Association (Thailand) to represent Thailand at the Lombok International Dance Sports Festival 2015 held at Lombok, Indonesia. The team has been awarded the Second Place in the Traditional Dance category.

Keywords: creative conservation process, cultural performing arts, Thatsana Nataya Chatri dance, competition

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Authors: Kingston Rajiah, Mari Kannan Maharajan, Si Jen Yeen, Sara Lew

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder with evolving layers of complexity. Both motor and non-motor symptoms of PD may affect patients’ quality of life (QoL). Life expectancy for an individual with Parkinson’s disease depends on the level of care the individual has access to, can have a direct impact on length of life. Therefore, improvement of the QoL is a significant part of therapeutic plans. Patients with PD, especially those who are in advanced stages, are in great need of assistance, mostly from their family members or caregivers in terms of medical, emotional, and social support. The role of a caregiver becomes increasingly important with the progression of PD, the severity of motor impairment and increasing age of the patient. The nature and symptoms associated with PD can place significant stresses on the caregivers’ burden. As the prevalence of PD is estimated to more than double by 2030, it is important to recognize and alleviate the burden experienced by caregivers. This study focused on the impact of the clinical features on the QoL of PD patients, and of their caregivers. This study included PD patients along with their caregivers and was undertaken at the Malaysian Parkinson's Disease Association from June 2016 to November 2016. Clinical features of PD patients were assessed using the Movement Disorder Society revised Unified Parkinson Disease Rating Scale (MDS-UPDRS); the Hoehn and Yahr Staging of Parkinson's Disease were used to assess the severity and Parkinson's disease activities of daily living scale were used to assess the disability of Parkinson’s disease patients. QoL of PD patients was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). The revised version of the Zarit Burden Interview assessed caregiver burden. At least one of the clinical features affected PD patients’ QoL, and at least one of the QoL domains affected the caregivers’ burden. Clinical features ‘Saliva and Drooling’, and ‘Dyskinesia’ explained 29% of variance in QoL of PD patients. The QoL domains ‘stigma’, along with ‘emotional wellbeing’ explained 48.6% of variance in caregivers’ burden. Clinical features such as saliva, drooling and dyskinesia affected the QoL of PD patients. The PD patients’ QoL domains such as ‘stigma’ and ‘emotional well-being’ influenced their caregivers’ burden.

Keywords: carers, quality of life, clinical features, Malaysia

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Authors: Denise Levy, Anna Lucia C. H. Villavicencio

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In a rapid-changing world, science teachers face considerable challenges. In addition to the basic curriculum, there must be included several transversal themes, which demand creative and innovative strategies to be arranged and integrated to traditional disciplines. In Brazil, nuclear science is still a controversial theme, and teachers themselves seem to be unaware of the issue, most often perpetuating prejudice, errors and misconceptions. This article presents the authors’ experience in the development of an interdisciplinary pedagogical proposal to include nuclear science in the basic curriculum, in a transversal and integrating way. The methodology applied was based on the analysis of several normative documents that define the requirements of essential learning, competences and skills of basic education for all schools in Brazil. The didactic materials and resources were developed according to the best practices to improve learning processes privileging constructivist educational techniques, with emphasis on active learning process, collaborative learning and learning through research. The material consists of an illustrated book for students, a book for teachers and a manual with activities that can articulate nuclear science to different disciplines: Portuguese, mathematics, science, art, English, history and geography. The content counts on high scientific rigor and articulate nuclear technology with topics of interest to society in the most diverse spheres, such as food supply, public health, food safety and foreign trade. Moreover, this pedagogical proposal takes advantage of the potential value of digital technologies, implementing QR codes that excite and challenge students of all ages, improving interaction and engagement. The expected results include the education of the educators for nuclear science communication in a transversal and integrating way, demystifying nuclear technology in a contextualized and significant approach. It is expected that the interdisciplinary pedagogical proposal contributes to improving attitudes towards knowledge construction, privileging reconstructive questioning, fostering a culture of systematic curiosity and encouraging critical thinking skills.

Keywords: science education, interdisciplinary learning, nuclear science, scientific literacy

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Authors: Gi-Young Park, Dong Rak Kwon, Sung Cheol Cho

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Objective: The synovium is known to be involved in many pathological characteristic processes. Also, synovitis is common in advanced osteoarthritis. We aimed to evaluate the clinical, radiographic, and ultrasound findings in patients with knee osteoarthritis and to compare the clinical and imaging findings between knee osteoarthritis with and without synovial hypertrophy confirmed by ultrasound. Methods: One hundred knees (54 left, 46 right) in 95 patients (64 women, 31 men; mean age, 65.9 years; range, 43-85 years) with knee osteoarthritis were recruited. The Visual Analogue Scale (VAS) was used to assess the intensity of knee pain. The severity of knee osteoarthritis was classified according to Kellgren and Lawrence's (K-L) grade on a radiograph. Ultrasound examination was performed by a physiatrist who had 24 years of experience in musculoskeletal ultrasound. Ultrasound findings, including the thickness of joint effusion in the suprapatellar pouch, synovial hypertrophy, infrapatellar tendinosis, meniscal tear or extrusion, and Baker cyst, were measured and detected. The thickness of knee joint effusion was measured at the maximal anterior-posterior diameter of fluid collection in the suprapatellar pouch. Synovial hypertrophy was identified as the soft tissue of variable echogenicity, which is poorly compressible and nondisplaceable by compression of an ultrasound transducer. The knees were divided into two groups according to the presence of synovial hypertrophy. The differences in clinical and imaging findings between the two groups were evaluated by independent t-test and chi-square test. Results: Synovial hypertrophy was detected in 48 knees of 100 knees on ultrasound. There were no significant differences in demographic parameters and VAS score except in sex between the two groups (P<0.05). Medial meniscal extrusion and tear were significantly more frequent in knees with synovial hypertrophy than those in knees without synovial hypertrophy. K-L grade and joint effusion thickness were greater in patients with synovial hypertrophy than those in patients without synovial hypertrophy (P<0.05). Conclusion: Synovial hypertrophy in knee osteoarthritis was associated with greater suprapatellar joint effusion and higher K-L grade and maybe a characteristic ultrasound feature of late knee osteoarthritis. These results suggest that synovial hypertrophy on ultrasound can be regarded as a predictor of rapid progression in patients with knee osteoarthritis.

Keywords: knee osteoarthritis, synovial hypertrophy, ultrasound, K-L grade

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Authors: Susanne Gustafsson

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Life-history research is an extraordinarily fruitful method to use for social analysis and gendered health analysis in particular. Its potential is illustrated through a case study drawn from a Swedish project. It reveals an old type of masculinity that faces difficulties when carrying out two sets of demands simultaneously, as a worker/manager and as a father/husband. The paper illuminates the historical transformation of masculinity and the consequences of this for health. We draw on the idea of the “changing faces of masculinity” to explore the dynamism and complexity of gendered health. An empirical case is used for its illustrative abilities. Jan, a middle-level manager and father employed in the energy sector in urban Sweden is the subject of this paper. Jan’s story is one of 32 semi-structured interviews included in an extended study focusing on well-being at work. The results reveal a face of masculinity conceived of in middle-level management as tacitly linked to the neoliberal doctrine. Over a couple of decades, the idea of “flexibility” was turned into a valuable characteristic that everyone was supposed to strive for. This resulted in increased workloads. Quite a few employees, and managers, in particular, find themselves working both day and night. This may explain why not having enough time to spend with children and family members is a recurring theme in the data. Can this way of doing be linked to masculinity and health? The first author’s research has revealed that the use of gender in health science is not sufficiently or critically questioned. This lack of critical questioning is a serious problem, especially since ways of doing gender affect health. We suggest that gender reproduction and gender transformation are interconnected, regardless of how they affect health. They are recognized as two sides of the same phenomenon, and minor movements in one direction or the other become crucial for understanding its relation to health. More or less, at the same time, as Jan’s masculinity was reproduced in response to workplace practices, Jan’s family position was transformed—not totally but by a degree or two, and these degrees became significant for the family’s health and well-being. By moving back and forth between varied events in Jan’s biographical history and his sociohistorical life span, it becomes possible to show that in a time of gender transformations, power relations can be renegotiated, leading to consequences for health.

Keywords: changing faces of masculinity, gendered health, life-history research method, subverter

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Rachel Falconer

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Background: The United Nations Convention on the Rights of the Child sets out the duties placed on signatory nations to take measures to protect children from all forms of violence, abuse, neglect and maltreatment. The systems for ensuring this protection vary globally, shaped by national welfare policies. In England and Finland, past research has highlighted differences in how child protection issues are framed and how state agencies respond. However, less is known about how such differences impact processes of social work judgment and decision making in practice. Method: Data was collected as part of a wider PhD project in three stages. First, social workers in sites across England and Finland were asked to complete a short questionnaire. Participants were then asked to comment on two constructed case vignettes, and were interviewed about their experiences of child protection decision making at the point of referral. Interviews were analyzed using NVivo to draw out key themes. Findings: There were similarities in how the English and Finnish social workers responded to the case vignettes; for example, participants in both countries expressed concerns about similar risk factors and all felt further assessment was needed. Differences were observed, in particular, in regard to the sources of support and guidance participants referred to, with the English social workers appearing to rely more upon managerial input for their decisions than the Finnish social workers. These findings suggest evidence for two distinct decision making approaches: ‘supervised’ and ‘supported’ judgement. Implications for practice: The findings have relevance to the conference theme of research and evaluation of social work practice, and support the findings of previous studies that have emphasized the significance of organizational factors in child protection decision making. The comparative methodology has also helped to demonstrate how organizational factors can influence practice in different child protection system ‘orientations’. The presentation will discuss the potential practice implications of ‘supervised’, manager-led approaches to decision making as contrasted with ‘supported’, team-led approaches, inviting discussion about the relevance of these findings for social work in other countries.

Keywords: child protection, comparative research, decision making, social work, vignettes

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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