Search results for: revealed comparative advantage
Commenced in January 2007
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Search results for: revealed comparative advantage

56 Schoolwide Implementation of Schema-Based Instruction for Mathematical Problem Solving: An Action Research Investigation

Authors: Sara J. Mills, Sally Howell

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The field of special education has long struggled to bridge the research to practice gap. There is ample evidence from research of effective strategies for students with special needs, but these strategies are not routinely implemented in schools in ways that yield positive results for students. In recent years, the field of special education has turned its focus to implementation science. That is, discovering effective methods of implementing evidence-based practices in school settings. Teacher training is a critical factor in implementation. This study aimed to successfully implement Schema-Based Instruction (SBI) for math problem solving in four classrooms in a special primary school serving students with language deficits, including students with Autism Spectrum Disorders (ASD) and Intellectual Disabilities (ID). Using an action research design that allowed for adjustments and modification to be made over the year-long study, two cohorts of teachers across the school were trained and supported in six-week learning cycles to implement SBI in their classrooms. The learning cycles included a one-day training followed by six weeks of one-on-one or team coaching and three fortnightly cohort group meetings. After the first cohort of teachers completed the learning cycle, modifications and adjustments were made to lesson materials in an attempt to improve their effectiveness with the second cohort. Fourteen teachers participated in the study, including master special educators (n=3), special education instructors (n=5), and classroom assistants (n=6). Thirty-one students participated in the study (21 boys and 10 girls), ranging in age from 5 to 12 years (M = 9 years). Twenty-one students had a diagnosis of ASD, 20 had a diagnosis of mild or moderate ID, with 13 of these students having both ASD and ID. The remaining students had diagnosed language disorders. To evaluate the effectiveness of the implementation approach, both student and teacher data was collected. Student data included pre- and post-tests of math word problem solving. Teacher data included fidelity of treatment checklists and pre-post surveys of teacher attitudes and efficacy for teaching problem solving. Finally, artifacts were collected throughout the learning cycle. Results from cohort 1 and cohort 2 revealed similar outcomes. Students improved in the number of word problems they answered correctly and in the number of problem-solving steps completed independently. Fidelity of treatment data showed that teachers implemented SBI with acceptable levels of fidelity (M = 86%). Teachers also reported increases in the amount of time spent teaching problem solving, their confidence in teaching problem solving and their perception of students’ ability to solve math word problems. The artifacts collected during instruction indicated that teachers made modifications to allow their students to access the materials and to show what they knew. These findings are in line with research that shows student learning can improve when teacher professional development is provided over an extended period of time, actively involves teachers, and utilizes a variety of learning methods in classroom contexts. Further research is needed to evaluate whether these gains in teacher instruction and student achievement can be maintained over time once the professional development is completed.

Keywords: implementation science, mathematics problem solving, research-to-practice gap, schema based instruction

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55 Implications of Agricultural Subsidies Since Green Revolution: A Case Study of Indian Punjab

Authors: Kriti Jain, Sucha Singh Gill

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Subsidies have been a major part of agricultural policies around the world, and more extensively since the green revolution in developing countries, for the sake of attaining higher agricultural productivity and achieving food security. But entrenched subsidies lead to distorted incentives and promote inefficiencies in the agricultural sector, threatening the viability of these very subsidies and sustainability of the agricultural production systems, posing a threat to the livelihood of farmers and laborers dependent on it. This paper analyzes the economic and ecological sustainability implications of prolonged input and output subsidies in agriculture by studying the case of Indian Punjab, an agriculturally developed state responsible for ensuring food security in the country when it was facing a major food crisis. The paper focuses specifically on the environmentally unsustainable cropping pattern changes as a result of Minimum Support Price (MSP) and assured procurement and on the resource use efficiency and cost implications of power subsidy for irrigation in Punjab. The study is based on an analysis of both secondary and primary data sources. Using secondary data, a time series analysis was done to capture the changes in Punjab’s cropping pattern, water table depth, fertilizer consumption, and electrification of agriculture. This has been done to examine the role of price and output support adopted to encourage the adoption of green revolution technology in changing the cropping structure of the state, resulting in increased input use intensities (especially groundwater and fertilizers), which harms the ecological balance and decreases factor productivity. Evaluation of electrification of Punjab agriculture helped evaluate the trend in electricity productivity of agriculture and how free power imposed further pressure on the extant agricultural ecosystem. Using data collected from a primary survey of 320 farmers in Punjab, the extent of wasteful application of groundwater irrigation, water productivity of output, electricity usage, and cost of irrigation driven electricity subsidy to the exchequer were estimated for the dominant cropping pattern amongst farmers. The main findings of the study revealed how because of a subsidy has driven agricultural framework, Punjab has lost area under agro climatically suitable and staple crops and moved towards a paddy-wheat cropping system, that is gnawing away the state’s natural resources like water table has been declining at a significant rate of 25 cms per year since 1975-76, and excessive and imbalanced fertilizer usage has led to declining soil fertility in the state. With electricity-driven tubewells as the major source of irrigation within a regime of free electricity and water-intensive crop cultivation, there is both wasteful application of irrigation water and electricity in the cultivation of paddy crops, burning an unproductive hole in the exchequer’s pocket. There is limited access to both agricultural extension services and water-conserving technology, along with policy imbalance, keeping farmers in an intensive and unsustainable production system. Punjab agriculture is witnessing diminishing returns to factor, which under the business-as-usual scenario, will soon enter the phase of negative returns to factor.

Keywords: cropping pattern, electrification, subsidy, sustainability

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54 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

Abstract:

Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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53 Septic Pulmonary Emboli as a Complication of Peripheral Venous Cannula Insertion

Authors: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

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Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

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52 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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51 Production of Insulin Analogue SCI-57 by Transient Expression in Nicotiana benthamiana

Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

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The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

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50 Classical Improvisation Facilitating Enhanced Performer-Audience Engagement and a Mutually Developing Impulse Exchange with Concert Audiences

Authors: Pauliina Haustein

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Improvisation was part of Western classical concert culture and performers’ skill sets until early 20th century. Historical accounts, as well as recent studies, indicate that improvisatory elements in the programme may contribute specifically towards the audiences’ experience of enhanced emotional engagement during the concert. This paper presents findings from the author’s artistic practice research, which explored re-introducing improvisation to Western classical performance practice as a musician (cellist and ensemble partner/leader). In an investigation of four concert cycles, the performer-researcher sought to gain solo and chamber music improvisation techniques (both related to and independent of repertoire), conduct ensemble improvisation rehearsals, design concerts with an improvisatory approach, and reflect on interactions with audiences after each concert. Data was collected through use of reflective diary, video recordings, measurement of sound parameters, questionnaires, a focus group, and interviews. The performer’s empirical experiences and findings from audience research components were juxtaposed and interrogated to better understand the (1) rehearsal and planning processes that enable improvisatory elements to return to Western classical concert experience and (2) the emotional experience and type of engagement that occur throughout the concert experience for both performer and audience members. This informed the development of a concert model, in which a programme of solo and chamber music repertoire and improvisations were combined according to historically evidenced performance practice (including free formal solo and ensemble improvisations based on audience suggestions). Inspired by historical concert culture, where elements of risk-taking, spontaneity, and audience involvement (such as proposing themes for fantasies) were customary, this concert model invited musicians to contribute to the process personally and creatively at all stages, from programme planning, and throughout the live concert. The type of democratic, personal, creative, and empathetic collaboration that emerged, as a result, appears unique in Western classical contexts, rather finding resonance in jazz ensemble, drama, or interdisciplinary settings. The research identified features of ensemble improvisation, such as empathy, emergence, mutual engagement, and collaborative creativity, that became mirrored in audience’s responses, generating higher levels of emotional engagement, empathy, inclusivity, and a participatory, co-creative experience. It appears that duringimprovisatory moments in the concert programme, audience members started feeling more like active participants in za\\a creative, collaborative exchange and became stakeholders in a deeper phenomenon of meaning-making and narrativization. Examining interactions between all involved during the concert revealed that performer-audience impulse exchange occurred on multiple levels of awareness and seemed to build upon each other, resulting in particularly strong experiences of both performer and audience’s engagement. This impact appeared especially meaningful for audience members who were seldom concertgoers and reported little familiarity with classical music. The study found that re-introducing improvisatory elements to Western classical concert programmes has strong potential in increasing audience’s emotional engagement with the musical performance, enabling audience members to connect more personally with the individual performers, and in reaching new-to-classical-music audiences.

Keywords: artistic research, audience engagement, audience experience, classical improvisation, ensemble improvisation, emotional engagement, improvisation, improvisatory approach, musical performance, practice research

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49 Even When the Passive Resistance Is Obligatory: Civil Intellectuals’ Solidarity Activism in Tea Workers Movement

Authors: Moshreka Aditi Huq

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This study shows how a progressive portion of civil intellectuals in Bangladesh contributed as the solidarity activist entities in a movement of tea workers that became the symbol of their unique moral struggle. Their passive yet sharp way of resistance, with the integration of mass tea workers of a tea estate, got demonstrated against certain private companies and government officials who approached to establish a special economic zone inside the tea garden without offering any compensation and rehabilitation for poor tea workers. Due to massive protests and rebellion, the authorized entrepreneurs had to step back and called off the project immediately. The extraordinary features of this movement generated itself from the deep core social need of indigenous tea workers who are still imprisoned in the colonial cage. Following an anthropological and ethnographic perspective, this study adopted the main three techniques of intensive interview, focus group discussion, and laborious observation, to extract empirical data. The intensive interviews were undertaken informally using a mostly conversational approach. Focus group discussions were piloted among various representative groups where observations prevailed as part of the regular documentation process. These were conducted among civil intellectual entities, tea workers, tea estate authorities, civil service authorities, and business officials to obtain a holistic view of the situation. The fieldwork was executed in capital Dhaka city, along with northern areas like Chandpur-Begumkhan Tea Estate of Chunarughat Upazilla and Habiganj city of Habiganj District of Bangladesh. Correspondingly, secondary data were accessed through books, scholarly papers, archives, newspapers, reports, leaflets, posters, writing blog, and electronic pages of social media. The study results find that: (1) civil intellectuals opposed state-sponsored business impositions by producing counter-discourse and struggled against state hegemony through the phases of the movement; (2) instead of having the active physical resistance, civil intellectuals’ strength was preferably in passive form which was portrayed through their intellectual labor; (3) the combined movement of tea workers and civil intellectuals reflected on social security of ethnic worker communities that contrasts state’s pseudo-development motives which ultimately supports offensive and oppressive neoliberal growths of economy; (4) civil intellectuals are revealed as having certain functional limitations in the process of movement organization as well as resource mobilization; (5) in specific contexts, the genuine need of protest by indigenous subaltern can overshadow intellectual elitism and helps to raise the voices of ‘subjugated knowledge’. This study is quite likely to represent two sets of apparent protagonist entities in the discussion of social injustice and oppressive development intervention. On the one, hand it may help us to find the basic functional characteristics of civil intellectuals in Bangladesh when they are in a passive mode of resistance in social movement issues. On the other hand, it represents the community ownership and inherent protest tendencies of indigenous workers when they feel threatened and insecure. The study seems to have the potential to understand the conditions of ‘subjugated knowledge’ of subalterns. Furthermore, being the memory and narratives, these ‘activism mechanisms’ of social entities broadens the path to understand ‘power’ and ‘resistance’ in more fascinating ways.

Keywords: civil intellectuals, resistance, subjugated knowledge, indigenous

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48 Chronic Progressive External Ophthalmoplegia (CPEO)

Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu

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INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.

Keywords: neurology, chronic, progressive, ophthalmoplegia

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47 Sustainable Urban Regenaration the New Vocabulary and the Timless Grammar of the Urban Tissue

Authors: Ruth Shapira

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Introduction: The rapid urbanization of the last century confronts planners, regulatory bodies, developers and most of all the public with seemingly unsolved conflicts regarding values, capital, and wellbeing of the built and un-built urban space. There is an out of control change of scale of the urban form and of the rhythm of the urban life which has known no significant progress in the last 2-3 decades despite the on-growing urban population. It is the objective of this paper to analyze some of these fundamental issues through the case study of a relatively small town in the center of Israel (Kiryat-Ono, 36,000 inhabitants), unfold the deep structure of qualities versus disruptors, present some cure that we have developed to bridge over and humbly suggest a practice that may bring about a sustainable new urban environment based on timeless values of the past, an approach that can be generic for similar cases. Basic Methodologies:The object, the town of Kiryat Ono, shall be experimented upon in a series of four action processes: De-composition, Re-composition, the Centering process and, finally, Controlled Structural Disintegration. Each stage will be based on facts, analysis of previous multidisciplinary interventions on various layers – and the inevitable reaction of the OBJECT, leading to the conclusion based on innovative theoretical and practical methods that we have developed and that we believe are proper for the open ended network, setting the rules for the contemporary urban society to cluster by – thus – a new urban vocabulary based on the old structure of times passed. The Study: Kiryat Ono, was founded 70 years ago as an agricultural settlement and rapidly turned into an urban entity. In spite the massive intensification, the original DNA of the old small town was still deeply embedded, mostly in the quality of the public space and in the sense of clustered communities. In the past 20 years, the recent demand for housing has been addressed to on the national level with recent master plans and urban regeneration policies mostly encouraging individual economic initiatives. Unfortunately, due to the obsolete existing planning platform the present urban renewal is characterized by pressure of developers, a dramatic change in building scale and widespread disintegration of the existing urban and social tissue.Our office was commissioned to conceptualize two master plans for the two contradictory processes of Kiryat Ono’s future: intensification and conservation. Following a comprehensive investigation into the deep structures and qualities of the existing town, we developed a new vocabulary of conservation terms thus redefying the sense of PLACE. The main challenge was to create master plans that should offer a regulatory basis to the accelerated and sporadic development providing for the public good and preserving the characteristics of the place consisting of a tool box of design guidelines that will have the ability to reorganize space along the time axis in a sustainable way. In conclusion: The system of rules that we have developed can generate endless possible patterns making sure that at each implementation fragment an event is created, and a better place is revealed. It takes time and perseverance but it seems to be the way to provide a healthy and sustainable framework for the accelerated urbanization of our chaotic present.

Keywords: sustainable urban design, intensification, emergent urban patterns, sustainable housing, compact urban neighborhoods, sustainable regeneration, restoration, complexity, uncertainty, need for change, implications of legislation on local planning

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46 Phytochemical Investigation, Leaf Structure and Antimicrobial Screening of Pistacia lentiscus against Multi-Drug Resistant Bacteria

Authors: S. Mamoucha, N.Tsafantakis, T. Ioannidis, S. Chatzipanagiotou, C. Nikolaou, L. Skaltsounis, N. Fokialakis, N. Christodoulakis

Abstract:

Introduction: Pistacia lentiscus L. (well known as Mastic tree) is an evergreen sclerophyllous shrub that extensively thrives in the eastern Mediterranean area yet only the trees cultivated in the southern region of the Greek island Chios produces mastic resin. Different parts of P. lentiscus L. var. chia have been used in folk medicine for various purposes, such as tonic, aphrodisiac, antiseptic, antihypertensive and management of dental, gastrointestinal, liver, urinary, and respiratory tract disorders. Several studies have focused on the antibacterial activity of its resin (gum) and its essential oil. However, there is no study combining anatomy of the plant organs, phytochemical profile, and antibacterial screening of the plant. In our attempt to discover novel bioactive metabolites from the mastic tree, we screened its antibacterial activity not only against ATCC strains but also against clinical, resistant strains. Materials-methods: Leaves were investigated using Transmission (ΤΕΜ) and Scanning Εlectron Microscopy (SEM). Histochemical tests were performed on fresh and fixed tissue. Extracts prepared from dried, powdered leaves using 3 different solvents (DCM, MeOH and H2O) the waste water obtained after a hydrodistillation process for essential oil production were screened for their phytochemical content and antibacterial activity. Μetabolite profiling of polar and non-polar extracts was recorded by GC-MS and LC-HRMS techniques and analyzed using in-house and commercial libraries. The antibacterial screening was performed against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853 and against clinical, resistant strains Methicillin-resistant S. aureus (MRSA), Carbapenem-Resistant Metallo-β-Lactamase (carbapenemase) P. aeruginosa (VIM), Klebsiella pneumoniae carbapenemases (KPCs) and Acinetobacter baumanii resistant strains. The antibacterial activity was tested by the Kirby Bauer and the Agar Well Diffusion method. The zone of inhibition (ZI) of each extract was measured and compared with those of common antibiotics. Results: Leaf is compact with inosclereids and numerous idioblasts containing a globular, spiny crystal. The major nerves of the leaf contain a resin duct. Mesophyll cells showed accumulation of osmiophillic metabolites. Histochemical treatments defined secondary metabolites in subcellular localization. The phytochemical investigation revealed the presence of a large number of secondary metabolites, belonging to different chemical groups, such as terpenoids, phenolic compounds (mainly myricetin, kaempferol and quercetin glycosides), phenolic, and fatty acids. Among the extracts, the hydrostillation wastewater achieved the best results against most of the bacteria tested. MRSA, VIM and A. baumanii were inhibited. Conclusion: Extracts from plants have recently been of great interest with respect to their antimicrobial activity. Their use emerged from a growing tendency to replace synthetic antimicrobial agents with natural ones. Leaves of P. lentiscus L. var. chia showed a high antimicrobial activity even against drug - resistant bacteria. Future prospects concern the better understanding of mode of action of the antibacterial activity, the isolation of the most bioactive constituents and the clarification if the activity is related to a single compound or to the synergistic effect of several ones.

Keywords: antibacterial screening, leaf anatomy, phytochemical profile, Pistacia lentiscus var. chia

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45 Phytochemical Profile and in Vitro Bioactivity Studies on Two Underutilized Vegetables in Nigeria

Authors: Borokini Funmilayo Boede

Abstract:

B. alba L., commonly called ‘Amunututu’ and Solanecio biafrae called ‘Worowo’ among the Yoruba tribe in the southwest part of Nigeria are reported to be of great ethnomedicinal importance but are among many underutilized green leafy vegetables in the country. Many studies have established the nutritional values of these vegetables, utilization are very poor and indepth information on their chemical profiles is scarce. The aqueous, methanolic and ethanolic extracts of these vegetables were subjected to phytochemical screening and phenolic profiles of the alcoholic extracts were characterized by using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Total phenol and flavonoid contents were determined, antioxidant activities were evaluated using five in vitro assays to assess DPPH, nitric oxide and hydroxyl radical-scavenging abilities, as well as reducing power with ferric reducing antioxidant assay and phosphomolybdate method. The antibacterial activities of the extracts against Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhi were evaluated by using agar well diffusion method and the antifungal activity evaluated against food-associated filamentous fungi by using poisoned food technique with the aim of assessing their nutraceutical potentials to encourage their production and utilization. The results revealed the presence of saponnin, steroids, tannin, terpenoid and flavonoid as well as phenolic compounds: gallic acid, chlorogenic acid, caffeic acid, coumarin, rutin, quercitrin, quercetin and kaemferol. The vegetables showed varying concentration dependent reducing and radical scavenging abilities from weak to strong compared with gallic acid, rutin, trolox and ascorbic acid used as positive controls; the aqueous extracts which gave higher concentrations of total phenol displayed higher ability to reduce Fe (lll) to Fe (ll) and stronger inhibiting power against hydroxyl radical than the alcoholic extracts and in most cases exhibited more potency than the ascorbic acids used as positive controls, at the same concentrations, whereas, methanol and / or ethanol extracts were found to be more effective in scavenging 2, 2-diphenyl-1-picryl hydrazyl radical and showed higher ability to reduce Mo (VI) to Mo (V) in total antioxidant assay than the aqueous extracts. However, the inhibition abilities of all the extracts against nitric oxide were comparable with the ascorbic acid control at the same concentrations. There were strong positive correlations with total phenol (mg GAE/g) and total flavonoid (mg RE/g) contents in the range TFC (r=0.857- 0999 and r= 0.904-1.000) and TPC (r= 0.844- 0.992 and r= 0.900 -0.999) for Basella alba and Senecio biafrae respectively. Inhibition concentration at 50 % (IC50) for each extract to scavenge DPPH, OH and NO radicals ranged from 32.73 to 1.52 compared with control (0.846 - -6.42) mg/ml. At 0.05g/ml, the vegetables were found to exhibit mild antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi compared with streptomycin sulphate used as control but appreciable antifungi activities against (Trichoderma rubrum and Aspergillus fumigates) compared with bonlate antibiotic positive control. The vegetables possess appreciable antioxidant and antimicrobial properties for promoting good health, their cultivation and utilization should be encouraged especially in the face of increasing health and economic challenges and food insecurity in many parts of the world.

Keywords: antimicrobial, antioxidants, extracts, phytochemicals

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44 High Performance Lithium Ion Capacitors from Biomass Waste-Derived Activated Carbon

Authors: Makhan Maharjan, Mani Ulaganathan, Vanchiappan Aravindan, Srinivasan Madhavi, Jing-Yuan Wang, Tuti Mariana Lim

Abstract:

The ever-increasing energy demand has made research to develop high performance energy storage systems that are able to fulfill energy needs. Supercapacitors have potential applications as portable energy storage devices. In recent years, there have been huge research interests to enhance the performances of supercapacitors via exploiting novel promising carbon precursors, tailoring textural properties of carbons, exploiting various electrolytes and device types. In this work, we employed orange peel (waste material) as the starting material and synthesized activated carbon by pyrolysis of KOH impregnated orange peel char at 800 °C in argon atmosphere. The resultant orange peel-derived activated carbon (OP-AC) exhibited BET surface area of 1,901 m² g-1, which is the highest surface area so far reported for the orange peel. The pore size distribution (PSD) curve exhibits the pores centered at 11.26 Å pore width, suggesting dominant microporosity. The high surface area OP-AC accommodates more ions in the electrodes and its well-developed porous structure facilitates fast diffusion of ions which subsequently enhance electrochemical performance. The OP-AC was studied as positive electrode in combination with different negative electrode materials, such as pre-lithiated graphite (LiC6) and Li4Ti5O12 for making hybrid capacitors. The lithium ion capacitor (LIC) fabricated using OP-AC with pre-lithiated graphite delivered high energy density of ~106 Wh kg–1. The energy density for OP-AC||Li4Ti5O12 capacitor was ~35 Wh kg⁻¹. For comparison purpose, configuration of OP-AC||OP-AC capacitors were studied in both aqueous (1M H2SO4) and organic (1M LiPF6 in EC-DMC) electrolytes, which delivered the energy density of 8.0 Wh kg⁻¹ and 16.3 Wh kg⁻¹, respectively. The cycling retentions obtained at current density of 1 A g⁻¹ were ~85.8, ~87.0 ~82.2 and ~58.8% after 2500 cycles for OP-AC||OP-AC (aqueous), OP-AC||OP-AC (organic), OP-AC||Li4Ti5O12 and OP-AC||LiC6 configurations, respectively. In addition, characterization studies were performed by elemental and proximate composition, thermogravimetry analysis, field emission-scanning electron microscopy, Raman spectra, X-ray diffraction (XRD) pattern, Fourier transform-infrared, X-ray photoelectron spectroscopy (XPS) and N2 sorption isotherms. The morphological features from FE-SEM exhibited well-developed porous structures. Two typical broad peaks observed in the XRD framework of the synthesized carbon implies amorphous graphitic structure. The ratio of 0.86 for ID/IG in Raman spectra infers high degree of graphitization in the sample. The band spectra of C 1s in XPS display the well resolved peaks related to carbon atoms in various chemical environments. The presence of functional groups is also corroborated from the FTIR spectroscopy. Characterization studies revealed the synthesized carbon to be promising electrode material towards the application for energy storage devices. Overall, the intriguing properties of OP-AC make it a new alternative promising electrode material for the development of high energy lithium ion capacitors from abundant, low-cost, renewable biomass waste. The authors gratefully acknowledge Agency for Science, Technology and Research (A*STAR)/ Singapore International Graduate Award (SINGA) and Nanyang Technological University (NTU), Singapore for funding support.

Keywords: energy storage, lithium-ion capacitors, orange peels, porous activated carbon

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43 Using Health Literacy and Medico-Legal Guidance to Improve Restorative Dentistry Patient Information Leaflets

Authors: Hasneet K. Kalsi, Julie K. Kilgariff

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Introduction: Within dentistry, the process for gaining informed consent has become more complex. To consent for treatment, patients must understand all reasonable treatment options and associated risks and benefits. Consenting is therefore deeply embedded in health literacy. Patients attending for dental consultation are often presented with an array of information and choices, yet studies show patients recall less than half of the information provided immediately after. Appropriate and comprehensible patient information leaflets (PILs) may be useful aid memories. In 2016 the World Health Organisation set improving health literacy as a global priority. Soon after, Scotland’s 2017-2025 Making it Easier: A Health Literacy Action Plan followed. This project involved the review of Restorative PILs used within Dundee Dental Hospital to assess the Content and Readability. Method: The current PIL on Root Canal Treatment (RCT) was created in 2011. This predates the Montgomery vs. NHS Lanarkshire case, a ruling which significantly impacted dental consenting processes, as well as General Dental Council’s (GDC’s) Standards for the Dental Team and Faculty of General Dental Practice’s Good Practice Guidance on Clinical Examination and Record-Keeping. Current evidence-based guidance, including that stipulated by the GDC, was reviewed. A 20-point Essential Content Checklist was designed to conform to best practice guidance for valid consenting processes. The RCT leaflet was scored against this to ascertain if the content was satisfactory. Having ensured the content satisfied medicolegal requirements, health literacy considerations were reviewed regarding readability. This was assessed using McLaughlin’s Simple Measure of Gobbledygook (SMOG) formula, which identifies school stages that would have to be achieved to comprehend the PIL. The sensitivity of the results to alternative readability methods were assessed. Results: The PIL was not sufficient for modern consenting processes and reflected a suboptimal level of health literacy. Evaluation of the leaflet revealed key content was missing, including information pertaining to risks and benefits. Only five points out of the 20-point checklist were present. The readability score was 16, equivalent to a level 2 in National Adult Literacy Standards/Scottish Credit and Qualification Framework Level 5; 62% of Scottish adults are able to read to this standard. Discussion: Assessment of the leaflet showed it was no longer fit for purpose. Reasons include a lack of pertinent information, a text-heavy leaflet lacking flow, and content errors. The SMOG score indicates a high level of comprehension is required to understand this PIL, which many patients may not possess. A new PIL, compliant with medicolegal and health literacy guidance, was designed with patient-driven checklists, notes spaces for annotations/ questions and areas for clinicians to highlight important case-specific information. It has been tested using the SMOG formula. Conclusion: PILs can be extremely useful. Studies show that interactive use can enhance their effectiveness. PILs should reflect best practice guidance and be understood by patients. The 2020 leaflet designed and implemented aims to fulfill the needs of a modern healthcare system and its service users. It embraces and embeds Scotland’s Health Literacy Action Plan within the consenting process. A review of further leaflets using this model is ongoing.

Keywords: consent, health literacy, patient information leaflet, restorative dentistry

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42 The Semiotics of Soft Power; An Examination of the South Korean Entertainment Industry

Authors: Enya Trenholm-Jensen

Abstract:

This paper employs various semiotic methodologies to examine the mechanism of soft power. Soft power refers to a country’s global reputation and their ability to leverage that reputation to achieve certain aims. South Korea has invested heavily in their soft power strategy for a multitude of predominantly historical and geopolitical reasons. On account of this investment and the global prominence of their strategy, South Korea was considered to be the optimal candidate for the aims of this investigation. Having isolated the entertainment industry as one of the most heavily funded segments of the South Korean soft power strategy, the analysis restricted itself to this sector. Within this industry, two entertainment products were selected as case studies. The case studies were chosen based on commercial success according to metrics such as streams, purchases, and subsequent revenue. This criterion was deemed to be the most objective and verifiable indicator of the products general appeal. The entertainment products which met the chosen criterion were Netflix’ “Squid Game” and BTS’ hit single “Butter”. The methodologies employed were chosen according to the medium of the entertainment products. For “Squid Game,” an aesthetic analysis was carried out to investigate how multi- layered meanings were mobilized in a show popularized by its visual grammar. To examine “Butter”, both music semiology and linguistic analysis were employed. The music section featured an analysis underpinned by denotative and connotative music semiotic theories borrowing from scholars Theo van Leeuwen and Martin Irvine. The linguistic analysis focused on stance and semantic fields according to scholarship by George Yule and John W. DuBois. The aesthetic analysis of the first case study revealed intertextual references to famous artworks, which served to augment the emotional provocation of the Squid Game narrative. For the second case study, the findings exposed a set of musical meaning units arranged in a patchwork of familiar and futuristic elements to achieve a song that existed on the boundary between old and new. The linguistic analysis of the song’s lyrics found a deceptively innocuous surface level meaning that bore implications for authority, intimacy, and commercial success. Whether through means of visual metaphor, embedded auditory associations, or linguistic subtext, the collective findings of the three analyses exhibited a desire to conjure a form of positive arousal in the spectator. In the synthesis section, this process is likened to that of branding. Through an exploration of branding, the entertainment products can be understood as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept. Limitations in the form of a timeframe biased perspective are addressed, and directions for future research are suggested. This paper employs semiotic methodologies to examine two entertainment products as mechanisms of soft power. Through means of visual metaphor, embedded auditory associations, or linguistic subtext, the findings reveal a desire to conjure positive arousal in the spectator. The synthesis finds similarities to branding, thus positioning the entertainment products as cogs in a larger operation aiming to create positive associations to Korea as a country and a concept.

Keywords: BTS, cognitive semiotics, entertainment, soft power, south korea, squid game

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41 A Multivariate Exploratory Data Analysis of a Crisis Text Messaging Service in Order to Analyse the Impact of the COVID-19 Pandemic on Mental Health in Ireland

Authors: Hamda Ajmal, Karen Young, Ruth Melia, John Bogue, Mary O'Sullivan, Jim Duggan, Hannah Wood

Abstract:

The Covid-19 pandemic led to a range of public health mitigation strategies in order to suppress the SARS-CoV-2 virus. The drastic changes in everyday life due to lockdowns had the potential for a significant negative impact on public mental health, and a key public health goal is to now assess the evidence from available Irish datasets to provide useful insights on this issue. Text-50808 is an online text-based mental health support service, established in Ireland in 2020, and can provide a measure of revealed distress and mental health concerns across the population. The aim of this study is to explore statistical associations between public mental health in Ireland and the Covid-19 pandemic. Uniquely, this study combines two measures of emotional wellbeing in Ireland: (1) weekly text volume at Text-50808, and (2) emotional wellbeing indicators reported by respondents of the Amárach public opinion survey, carried out on behalf of the Department of Health, Ireland. For this analysis, a multivariate graphical exploratory data analysis (EDA) was performed on the Text-50808 dataset dated from 15th June 2020 to 30th June 2021. This was followed by time-series analysis of key mental health indicators including: (1) the percentage of daily/weekly texts at Text-50808 that mention Covid-19 related issues; (2) the weekly percentage of people experiencing anxiety, boredom, enjoyment, happiness, worry, fear and stress in Amárach survey; and Covid-19 related factors: (3) daily new Covid-19 case numbers; (4) daily stringency index capturing the effect of government non-pharmaceutical interventions (NPIs) in Ireland. The cross-correlation function was applied to measure the relationship between the different time series. EDA of the Text-50808 dataset reveals significant peaks in the volume of texts on days prior to level 3 lockdown and level 5 lockdown in October 2020, and full level 5 lockdown in December 2020. A significantly high positive correlation was observed between the percentage of texts at Text-50808 that reported Covid-19 related issues and the percentage of respondents experiencing anxiety, worry and boredom (at a lag of 1 week) in Amárach survey data. There is a significant negative correlation between percentage of texts with Covid-19 related issues and percentage of respondents experiencing happiness in Amárach survey. Daily percentage of texts at Text-50808 that reported Covid-19 related issues to have a weak positive correlation with daily new Covid-19 cases in Ireland at a lag of 10 days and with daily stringency index of NPIs in Ireland at a lag of 2 days. The sudden peaks in text volume at Text-50808 immediately prior to new restrictions in Ireland indicate an association between a rise in mental health concerns following the announcement of new restrictions. There is also a high correlation between emotional wellbeing variables in the Amárach dataset and the number of weekly texts at Text-50808, and this confirms that Text-50808 reflects overall public sentiment. This analysis confirms the benefits of the texting service as a community surveillance tool for mental health in the population. This initial EDA will be extended to use multivariate modeling to predict the effect of additional Covid-19 related factors on public mental health in Ireland.

Keywords: COVID-19 pandemic, data analysis, digital health, mental health, public health, digital health

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40 Effects of Delphinidin on Lipid Metabolism in HepG2 Cells and Diet-Induced Obese Mice

Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

Abstract:

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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39 The Use of Antioxidant and Antimicrobial Properties of Plant Extracts for Increased Safety and Sustainability of Dairy Products

Authors: Loreta Serniene, Dalia Sekmokiene, Justina Tomkeviciute, Lina Lauciene, Vaida Andruleviciute, Ingrida Sinkeviciene, Kristina Kondrotiene, Neringa Kasetiene, Mindaugas Malakauskas

Abstract:

One of the most important areas of product development and research in the dairy industry is the product enrichment with active ingredients as well as leading to increased product safety and sustainability. The most expanding field of the active ingredients is the various plants' CO₂ extracts with aromatic, antioxidant and antimicrobial properties. In this study, 15 plant extracts were evaluated based on their antioxidant, antimicrobial properties as well as sensory acceptance indicators for the development of new dairy products. In order to increase the total antioxidant capacity of the milk products, it was important to determine the content of phenolic compounds and antioxidant activity of CO₂ extract. The total phenolic content of fifteen different commercial CO₂ extracts was determined by the Folin-Ciocalteu reagent and expressed as milligrams of the Gallic acid equivalents (GAE) in gram of extract. The antioxidant activities were determined by 2.2′-azinobis-(3-ethylbenzthiazoline)-6-sulfonate (ABTS) methods. The study revealed that the antioxidant activities of investigated CO₂ extract vary from 4.478-62.035 µmole Trolox/g, while the total phenolic content was in the range of 2.021-38.906 mg GAE/g of extract. For the example, the estimated antioxidant activity of Chinese cinnamon (Cinammonum aromaticum) CO₂ extract was 62.023 ± 0.15 µmole Trolox/g and the total flavonoid content reached 17.962 ± 0.35 mg GAE/g. These two parameters suggest that cinnamon could be a promising supplement for the development of new cheese. The inhibitory effects of these essential oils were tested by using agar disc diffusion method against pathogenic bacteria, most commonly found in dairy products. The obtained results showed that essential oil of lemon myrtle (Backhousia citriodora) and cinnamon (Cinnamomum cassia) has antimicrobial activity against E. coli, S. aureus, B. cereus, P. florescens, L. monocytogenes, Br. thermosphacta, P. aeruginosa and S. typhimurium with the diameter of inhibition zones variation from 10 to 52 mm. The sensory taste acceptability of plant extracts in combination with a dairy product was evaluated by a group of sensory evaluation experts (31 individuals) by the criteria of overall taste acceptability in the scale of 0 (not acceptable) to 10 (very acceptable). Each of the tested samples included 200g grams of natural unsweetened greek yogurt without additives and 1 drop of single plant extract (essential oil). The highest average of overall taste acceptability was defined for the samples with essential oils of orange (Citrus sinensis) - average score 6.67, lemon myrtle (Backhousia citriodora) – 6.62, elderberry flower (Sambucus nigra flos.) – 6.61, lemon (Citrus limon) – 5.75 and cinnamon (Cinnamomum cassia) – 5.41, respectively. The results of this study indicate plant extracts of Cinnamomum cassia and Backhousia citriodora as a promising additive not only to increase the total antioxidant capacity of the milk products and as alternative antibacterial agent to combat pathogenic bacteria commonly found in dairy products but also as a desirable flavour for the taste pallet of the consumers with expressed need for safe, sustainable and innovative dairy products. Acknowledgment: This research was funded by the European Regional Development Fund according to the supported activity 'Research Projects Implemented by World-class Researcher Groups' under Measure No. 01.2.2-LMT-K-718.

Keywords: antioxidant properties, antimicrobial properties, cinnamon, CO₂ plant extracts, dairy products, essential oils, lemon myrtle

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38 Genetic Diversity of Exon-20 of the IIS6 of the Voltage Gated Sodium Channel Gene from Pyrethroid Resistant Anopheles Mosquitoes in Sudan Savannah Region of Jigawa State

Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

Abstract:

Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

Procedia PDF Downloads 52
37 Provision of Afterschool Programs: Understanding the Educational Needs and Outcomes of Newcomer and Refugee Students in Canada

Authors: Edward Shizha, Edward Makwarimba

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Newcomer and refugee youth feel excluded in the education system in Canada, and the formal education environment does not fully cater for their learning needs. The objective of this study was to build knowledge and understanding of the educational needs and experiences of these youth in Canada and how available afterschool programs can most effectively support their learning needs and academic outcomes. The Employment and Social Development Canada (ESDC), which funded this research, enables and empowers students to advance their educational experience through targeted investments in services that are delivered by youth-serving organizations outside the formal education system through afterschool initiatives. A literature review and a provincial/territorial internet scan were conducted to determine the availability of services and programs that serve the educational needs and academic outcomes of newcomer youth in 10 provinces and 3 territories in Canada. The goal was to identify intersectional factors (e.g., gender, sexuality, culture, social class, race, etc.) that influence educational outcomes of newcomer/refugee students and to recommend ways the ESDC could complement settlement services to enhance students’ educational success. First, data was collected through a literature search of various databases, including PubMed, Web of Science, Scopus, Google docs, ACADEMIA, and grey literature, including government documents, to inform our analysis. Second, a provincial/territorial internet scan was conducted using a template that was created by ESDC staff with the input of the researchers. The objective of the web-search scan was to identify afterschool programs, projects, and initiatives offered to newcomer/refugee youth by service provider organizations. The method for the scan included both qualitative and quantitative data gathering. Both the literature review and the provincial/territorial scan revealed that there are gender disparities in educational outcomes of newcomer and refugee youth. High school completion rates by gender show that boys are at higher risk of not graduating than girls and that girls are more likely than boys to have at least a high school diploma and more likely to proceed to postsecondary education. Findings from literature reveal that afterschool programs are required for refugee youth who experience mental health challenges and miss out on significant periods of schooling, which affect attendance, participation, and graduation from high school. However, some refugee youth use their resilience and ambition to succeed in their educational outcomes. Another finding showed that some immigrant/refugee students, through ethnic organizations and familial affiliation, maintain aspects of their cultural values, parental expectations and ambitious expectations for their own careers to succeed in both high school and postsecondary education. The study found a significant combination of afterschool programs that include academic support, scholarships, bursaries, homework support, career readiness, internships, mentorship, tutoring, non-clinical counselling, mental health and social well-being support, language skills, volunteering opportunities, community connections, peer networking, culturally relevant services etc. These programs assist newcomer youth to develop self-confidence and prepare for academic success and future career development. The study concluded that advantages of afterschool programs are greatest for youth at risk for poor educational outcomes, such as Latino and Black youth, including 2SLGBTQI+ immigrant youth.

Keywords: afterschool programs, educational outcomes, newcomer youth, refugee youth, youth-serving organizations

Procedia PDF Downloads 68
36 Biodegradation of Chlorophenol Derivatives Using Macroporous Material

Authors: Dmitriy Berillo, Areej K. A. Al-Jwaid, Jonathan L. Caplin, Andrew Cundy, Irina Savina

Abstract:

Chlorophenols (CPs) are used as a precursor in the production of higher CPs and dyestuffs, and as a preservative. Contamination by CPs of the ground water is located in the range from 0.15-100mg/L. The EU has set maximum concentration limits for pesticides and their degradation products of 0.1μg/L and 0.5μg/L, respectively. People working in industries which produce textiles, leather products, domestic preservatives, and petrochemicals are most heavily exposed to CPs. The International Agency for Research on Cancers categorized CPs as potential human carcinogens. Existing multistep water purification processes for CPs such as hydrogenation, ion exchange, liquid-liquid extraction, adsorption by activated carbon, forward and inverse osmosis, electrolysis, sonochemistry, UV irradiation, and chemical oxidation are not always cost effective and can cause the formation of even more toxic or mutagenic derivatives. Bioremediation of CPs derivatives utilizing microorganisms results in 60 to 100% decontamination efficiency and the process is more environmentally-friendly compared with existing physico-chemical methods. Microorganisms immobilized onto a substrate show many advantages over free bacteria systems, such as higher biomass density, higher metabolic activity, and resistance to toxic chemicals. They also enable continuous operation, avoiding the requirement for biomass-liquid separation. The immobilized bacteria can be reused several times, which opens the opportunity for developing cost-effective processes for wastewater treatment. In this study, we develop a bioremediation system for CPs based on macroporous materials, which can be efficiently used for wastewater treatment. Conditions for the preparation of the macroporous material from specific bacterial strains (Pseudomonas mendocina and Rhodococus koreensis) were optimized. The concentration of bacterial cells was kept constant; the difference was only the type of cross-linking agents used e.g. glutaraldehyde, novel polymers, which were utilized at concentrations of 0.5 to 1.5%. SEM images and rheology analysis of the material indicated a monolithic macroporous structure. Phenol was chosen as a model system to optimize the function of the cryogel material and to estimate its enzymatic activity, since it is relatively less toxic and harmful compared to CPs. Several types of macroporous systems comprising live bacteria were prepared. The viability of the cross-linked bacteria was checked using Live/Dead BacLight kit and Laser Scanning Confocal Microscopy, which revealed the presence of viable bacteria with the novel cross-linkers, whereas the control material cross-linked with glutaraldehyde(GA), contained mostly dead cells. The bioreactors based on bacteria were used for phenol degradation in batch mode at an initial concentration of 50mg/L, pH 7.5 and a temperature of 30°C. Bacterial strains cross-linked with GA showed insignificant ability to degrade phenol and for one week only, but a combination of cross-linking agents illustrated higher stability, viability and the possibility to be reused for at least five weeks. Furthermore, conditions for CPs degradation will be optimized, and the chlorophenol degradation rates will be compared to those for phenol. This is a cutting-edge bioremediation approach, which allows the purification of waste water from sustainable compounds without a separation step to remove free planktonic bacteria. Acknowledgments: Dr. Berillo D. A. is very grateful to Individual Fellowship Marie Curie Program for funding of the research.

Keywords: bioremediation, cross-linking agents, cross-linked microbial cell, chlorophenol degradation

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35 Magnetic Single-Walled Carbon Nanotubes (SWCNTs) as Novel Theranostic Nanocarriers: Enhanced Targeting and Noninvasive MRI Tracking

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

Abstract:

Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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34 Linking the Genetic Signature of Free-Living Soil Diazotrophs with Process Rates under Land Use Conversion in the Amazon Rainforest

Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

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The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

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33 Identification of a Panel of Epigenetic Biomarkers for Early Detection of Hepatocellular Carcinoma in Blood of Individuals with Liver Cirrhosis

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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32 Recurrent Torsades de Pointes Post Direct Current Cardioversion for Atrial Fibrillation with Rapid Ventricular Response

Authors: Taikchan Lildar, Ayesha Samad, Suraj Sookhu

Abstract:

Atrial fibrillation with rapid ventricular response results in the loss of atrial kick and shortened ventricular filling time, which often leads to decompensated heart failure. Pharmacologic rhythm control is the treatment of choice, and patients frequently benefit from the restoration of sinus rhythm. When pharmacologic treatment is unsuccessful or a patient declines hemodynamically, direct cardioversion is the treatment of choice. Torsades de pointes or “twisting of the points'' in French, is a rare but under-appreciated risk of cardioversion therapy and accounts for a significant number of sudden cardiac death each year. A 61-year-old female with no significant past medical history presented to the Emergency Department with worsening dyspnea. An electrocardiogram showed atrial fibrillation with rapid ventricular response, and a chest X-ray was significant for bilateral pulmonary vascular congestion. Full-dose anticoagulation and diuresis were initiated with moderate improvement in symptoms. A transthoracic echocardiogram revealed biventricular systolic dysfunction with a left ventricular ejection fraction of 30%. After consultation with an electrophysiologist, the consensus was to proceed with the restoration of sinus rhythm, which would likely improve the patient’s heart failure symptoms and possibly the ejection fraction. A transesophageal echocardiogram was negative for left atrial appendage thrombus; the patient was treated with a loading dose of amiodarone and underwent successful direct current cardioversion with 200 Joules. The patient was placed on telemetry monitoring for 24 hours and was noted to have frequent premature ventricular contractions with subsequent degeneration to torsades de pointes. The patient was found unresponsive and pulseless; cardiopulmonary resuscitation was initiated with cardioversion, and return of spontaneous circulation was achieved after four minutes to normal sinus rhythm. Post-cardiac arrest electrocardiogram showed sinus bradycardia with heart-rate corrected QT interval of 592 milliseconds. The patient continued to have frequent premature ventricular contractions and required two additional cardioversions to achieve a return of spontaneous circulation with intravenous magnesium and lidocaine. An automatic implantable cardioverter-defibrillator was subsequently implanted for secondary prevention of sudden cardiac death. The backup pacing rate of the automatic implantable cardioverter-defibrillator was set higher than usual in an attempt to prevent premature ventricular contractions-induced torsades de pointes. The patient did not have any further ventricular arrhythmias after implantation of the automatic implantable cardioverter-defibrillator. Overdrive pacing is a method utilized to treat premature ventricular contractions-induced torsades de pointes by preventing a patient’s susceptibility to R on T-wave-induced ventricular arrhythmias. Pacing at a rate of 90 beats per minute succeeded in controlling the arrhythmia without the need for traumatic cardiac defibrillation. In our patient, conversion of atrial fibrillation with rapid ventricular response to normal sinus rhythm resulted in a slower heart rate and an increased probability of premature ventricular contraction occurring on the T-wave and ensuing ventricular arrhythmia. This case highlights direct current cardioversion for atrial fibrillation with rapid ventricular response resulting in persistent ventricular arrhythmia requiring an automatic implantable cardioverter-defibrillator placement with overdrive pacing to prevent a recurrence.

Keywords: refractory atrial fibrillation, atrial fibrillation, overdrive pacing, torsades de pointes

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31 Analysis Of Fine Motor Skills in Chronic Neurodegenerative Models of Huntington’s Disease and Amyotrophic Lateral Sclerosis

Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

Abstract:

Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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30 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

Abstract:

In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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29 DH-Students Promoting Underage Asylum Seekers' Oral Health in Finland

Authors: Eeva Wallenius-Nareneva, Tuula Toivanen-Labiad

Abstract:

Background: Oral health promotion event was organised for forty Afghanistan, Iraqi and Bangladeshi underage asylum seekers in Finland. The invitation to arrange this coaching occasion was accepted in the Degree Programme in Oral Hygiene in Metropolia. The personnel in the reception center found the need to improve oral health among the youngsters. The purpose was to strengthen the health literacy of the boys in their oral self-care and to reduce dental fears. The Finnish studies, especially the terminology of oral health was integrated to coaching with the help of interpreters. Cooperative learning was applied. Methods: Oral health was interactively discussed in four study group sessions: 1. The importance of healthy eating habits; - Good and bad diets, - Regular meals, - Acid attack o Xylitol. 2. Oral diseases − connection to general health; - Aetiology of gingivitis, periodontitis and caries, - Harmfulness of smoking 3. Tools and techniques for oral self-care; - Brushing and inter dental cleaning. 4. Sharing earlier dental care experiences; - Cultural differences, - Dental fear, - Regular check-ups. Results: During coaching deficiencies appeared in brushing and inter dental cleaning techniques. Some boys were used to wash their mouth with salt justifying it by salt’s antiseptic properties. Many brushed their teeth by vertical movements. The boys took feedback positively when a demonstration with model jaws revealed the inefficiency of the technique. The advantages of fluoride tooth paste were advised. Dental care procedures were new and frightening for many boys. Finnish dental care system was clarified. The safety and indolence of the treatments and informed consent were highlighted. Video presentations and the dialog lowered substantially the threshold to visit dental clinic. The occasion gave the students means for meeting patients from different cultural and language backgrounds. The information hidden behind the oral health problems of the asylum seekers was valuable. Conclusions: Learning dental care practices used in different cultures is essential for dental professionals. The project was a good start towards multicultural oral health care. More experiences are needed before graduation. Health education themes should be held simple regardless of the target group. The heterogeneity of the group does not pose a problem. Open discussion with questions leading to the theme works well in clarifying the target group’s knowledge level. Sharing own experiences strengthens the sense of equality among the participants and encourages them to express own opinions. Motivational interview method turned out to be successful. In the future coaching occasions must confirm active participation of everyone. This could be realized by dividing the participants to even smaller groups. The different languages impose challenges but they can be solved by using more interpreters. Their presence ensures that everyone understands the issues properly although the use of plain and sign languages are helpful. In further development, it would be crucial to arrange a rehearsal occasion to the same participants in two/three months’ time. This would strengthen the adaption of self-care practices and give the youngsters opportunity to pose more open questions. The students would gain valuable feedback regarding the effectiveness of their work.

Keywords: cooperative learning, interactive methods, motivational interviewing, oral health promotion, underage asylum seekers

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28 Geospatial and Statistical Evidences of Non-Engineered Landfill Leachate Effects on Groundwater Quality in a Highly Urbanised Area of Nigeria

Authors: David A. Olasehinde, Peter I. Olasehinde, Segun M. A. Adelana, Dapo O. Olasehinde

Abstract:

An investigation was carried out on underground water system dynamics within Ilorin metropolis to monitor the subsurface flow and its corresponding pollution. Africa population growth rate is the highest among the regions of the world, especially in urban areas. A corresponding increase in waste generation and a change in waste composition from predominantly organic to non-organic waste has also been observed. Percolation of leachate from non-engineered landfills, the chief means of waste disposal in many of its cities, constitutes a threat to the underground water bodies. Ilorin city, a transboundary town in southwestern Nigeria, is a ready microcosm of Africa’s unique challenge. In spite of the fact that groundwater is naturally protected from common contaminants such as bacteria as the subsurface provides natural attenuation process, groundwater samples have been noted to however possesses relatively higher dissolved chemical contaminants such as bicarbonate, sodium, and chloride which poses a great threat to environmental receptors and human consumption. The Geographic Information System (GIS) was used as a tool to illustrate, subsurface dynamics and the corresponding pollutant indicators. Forty-four sampling points were selected around known groundwater pollutant, major old dumpsites without landfill liners. The results of the groundwater flow directions and the corresponding contaminant transport were presented using expert geospatial software. The experimental results were subjected to four descriptive statistical analyses, namely: principal component analysis, Pearson correlation analysis, scree plot analysis, and Ward cluster analysis. Regression model was also developed aimed at finding functional relationships that can adequately relate or describe the behaviour of water qualities and the hypothetical factors landfill characteristics that may influence them namely; distance of source of water body from dumpsites, static water level of groundwater, subsurface permeability (inferred from hydraulic gradient), and soil infiltration. The regression equations developed were validated using the graphical approach. Underground water seems to flow from the northern portion of Ilorin metropolis down southwards transporting contaminants. Pollution pattern in the study area generally assumed a bimodal pattern with the major concentration of the chemical pollutants in the underground watershed and the recharge. The correlation between contaminant concentrations and the spread of pollution indicates that areas of lower subsurface permeability display a higher concentration of dissolved chemical content. The principal component analysis showed that conductivity, suspended solids, calcium hardness, total dissolved solids, total coliforms, and coliforms were the chief contaminant indicators in the underground water system in the study area. Pearson correlation revealed a high correlation of electrical conductivity for many parameters analyzed. In the same vein, the regression models suggest that the heavier the molecular weight of a chemical contaminant of a pollutant from a point source, the greater the pollution of the underground water system at a short distance. The study concludes that the associative properties of landfill have a significant effect on groundwater quality in the study area.

Keywords: dumpsite, leachate, groundwater pollution, linear regression, principal component

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27 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

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