Search results for: heart failure reversal therapy
Commenced in January 2007
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Edition: International
Paper Count: 5159

Search results for: heart failure reversal therapy

29 Agenesis of the Corpus Callosum: The Role of Neuropsychological Assessment with Implications to Psychosocial Rehabilitation

Authors: Ron Dick, P. S. D. V. Prasadarao, Glenn Coltman

Abstract:

Agenesis of the corpus callosum (ACC) is a failure to develop corpus callosum - the large bundle of fibers of the brain that connects the two cerebral hemispheres. It can occur as a partial or complete absence of the corpus callosum. In the general population, its estimated prevalence rate is 1 in 4000 and a wide range of genetic, infectious, vascular, and toxic causes have been attributed to this heterogeneous condition. The diagnosis of ACC is often achieved by neuroimaging procedures. Though persons with ACC can perform normally on intelligence tests they generally present with a range of neuropsychological and social deficits. The deficit profile is characterized by poor coordination of motor movements, slow reaction time, processing speed and, poor memory. Socially, they present with deficits in communication, language processing, the theory of mind, and interpersonal relationships. The present paper illustrates the role of neuropsychological assessment with implications to psychosocial management in a case of agenesis of the corpus callosum. Method: A 27-year old left handed Caucasian male with a history of ACC was self-referred for a neuropsychological assessment to assist him in his employment options. Parents noted significant difficulties with coordination and balance at an early age of 2-3 years and he was diagnosed with dyspraxia at the age of 14 years. History also indicated visual impairment, hypotonia, poor muscle coordination, and delayed development of motor milestones. MRI scan indicated agenesis of the corpus callosum with ventricular morphology, widely spaced parallel lateral ventricles and mild dilatation of the posterior horns; it also showed colpocephaly—a disproportionate enlargement of the occipital horns of the lateral ventricles which might be affecting his motor abilities and visual defects. The MRI scan ruled out other structural abnormalities or neonatal brain injury. At the time of assessment, the subject presented with such problems as poor coordination, slowed processing speed, poor organizational skills and time management, and difficulty with social cues and facial expressions. A comprehensive neuropsychological assessment was planned and conducted to assist in identifying the current neuropsychological profile to facilitate the formulation of a psychosocial and occupational rehabilitation programme. Results: General intellectual functioning was within the average range and his performance on memory-related tasks was adequate. Significant visuospatial and visuoconstructional deficits were evident across tests; constructional difficulties were seen in tasks such as copying a complex figure, building a tower and manipulating blocks. Poor visual scanning ability and visual motor speed were evident. Socially, the subject reported heightened social anxiety, difficulty in responding to cues in the social environment, and difficulty in developing intimate relationships. Conclusion: Persons with ACC are known to present with specific cognitive deficits and problems in social situations. Findings from the current neuropsychological assessment indicated significant visuospatial difficulties, poor visual scanning and problems in social interactions. His general intellectual functioning was within the average range. Based on the findings from the comprehensive neuropsychological assessment, a structured psychosocial rehabilitation programme was developed and recommended.

Keywords: agenesis, callosum, corpus, neuropsychology, psychosocial, rehabilitation

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28 Confirming the Factors of Professional Readiness in Athletic Training

Authors: Philip A. Szlosek, M. Susan Guyer, Mary G. Barnum, Elizabeth M. Mullin

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In the United States, athletic training is a healthcare profession that encompasses the prevention, examination, diagnosis, treatment, and rehabilitation of injuries and medical conditions. Athletic trainers work under the direction of or in collaboration with a physician and are recognized by the American Medical Association as allied healthcare professionals. Internationally, this profession is often known as athletic therapy. As healthcare professionals, athletic trainers must be prepared for autonomous practice immediately after graduation. However, new athletic trainers have been shown to have clinical areas of strength and weakness.To better assess professional readiness and improve the preparedness of new athletic trainers, the factors of athletic training professional readiness must be defined. Limited research exists defining the holistic aspects of professional readiness needed for athletic trainers. Confirming the factors of professional readiness in athletic training could enhance the professional preparation of athletic trainers and result in more highly prepared new professionals. The objective of this study was to further explore and confirm the factors of professional readiness in athletic training. Authors useda qualitative design based in grounded theory. Participants included athletic trainers with greater than 24 months of experience from a variety of work settings from each district of the National Athletic Trainer’s Association. Participants took the demographic questionnaire electronically using Qualtrics Survey Software (Provo UT). After completing the demographic questionnaire, 20 participants were selected to complete one-on-one interviews using GoToMeeting audiovisual web conferencing software. IBM Statistical Package for the Social Sciences (SPSS, v. 21.0) was used to calculate descriptive statistics for participant demographics. The first author transcribed all interviews verbatim and utilized a grounded theory approach during qualitative data analysis. Data were analyzed using a constant comparative analysis and open and axial coding. Trustworthiness was established using reflexivity, member checks, and peer reviews. Analysis revealed four overarching themes, including management, interpersonal relations, clinical decision-making, and confidence. Management was categorized as athletic training services not involving direct patient care and was divided into three subthemes, including administration skills, advocacy, and time management. Interpersonal Relations was categorized as the need and ability of the athletic trainer to properly interact with others. Interpersonal relations was divided into three subthemes, including personality traits, communication, and collaborative practice. Clinical decision-making was categorized as the skills and attributes required by the athletic trainer whenmaking clinical decisions related to patient care. Clinical decision-making was divided into three subthemes including clinical skills, continuing education, and reflective practice. The final theme was confidence. Participants discussed the importance of confidence regarding relationships building, clinical and administrative duties, and clinical decision-making. Overall, participants explained the value of a well-rounded athletic trainer and emphasized that athletic trainers need communication and organizational skills, the ability to collaborate, and must value self-reflection and continuing education in addition to having clinical expertise. Future research should finalize a comprehensive model of professional readiness for athletic training, develop a holistic assessment instrument for athletic training professional readiness, and explore the preparedness of new athletic trainers.

Keywords: autonomous practice, newly certified athletic trainer, preparedness for professional practice, transition to practice skills

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27 Assessing Organizational Resilience Capacity to Flooding: Index Development and Application to Greek Small & Medium-Sized Enterprises

Authors: Antonis Skouloudis, Konstantinos Evangelinos, Walter Leal-Filho, Panagiotis Vouros, Ioannis Nikolaou

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Organizational resilience capacity to extreme weather events (EWEs) has sparked a growth in scholarly attention over the past decade as an essential aspect in business continuity management, with supporting evidence for this claim to suggest that it retains a key role in successful responses to adverse situations, crises and shocks. Small and medium-sized enterprises (SMEs) are more vulnerable to face floods compared to their larger counterparts, so they are disproportionately affected by such extreme weather events. The limited resources at their disposal, the lack of time and skills all conduce to inadequate preparedness to challenges posed by floods. SMEs tend to plan in the short-term, reacting to circumstances as they arise and focussing on their very survival. Likewise, they share less formalised structures and codified policies while they are most usually owner-managed, resulting in a command-and-control management culture. Such characteristics result in them having limited opportunities to recover from flooding and quickly turnaround their operation from a loss making to a profit making one. Scholars frame the capacity of business entities to be resilient upon an EWE disturbance (such as flash floods) as the rate of recovery and restoration of organizational performance to pre-disturbance conditions, the amount of disturbance (i.e. threshold level) a business can absorb before losing structural and/or functional components that will alter or cease operation, as well as the extent to which the organization maintains its function (i.e. impact resistance) before performance levels are driven to zero. Nevertheless, while it seems to be accepted as an essential trait of firms effectively transcending uncertain conditions, research deconstructing the enabling conditions and/or inhibitory factors of SMEs resilience capacity to natural hazards is still sparse, fragmentary and mostly fuelled by anecdotal evidence or normative assumptions. Focusing on the individual level of analysis, i.e. the individual enterprise and its endeavours to succeed, the emergent picture from this relatively new research strand delineates the specification of variables, conceptual relationships or dynamic boundaries of resilience capacity components in an attempt to provide prescriptions for policy-making as well as business management. This study will present the development of a flood resilience capacity index (FRCI) and its application to Greek SMEs. The proposed composite indicator pertains to cognitive, behavioral/managerial and contextual factors that influence an enterprise’s ability to shape effective responses to meet flood challenges. Through the proposed indicator-based approach, an analytical framework is set forth that will help standardize such assessments with the overarching aim of reducing the vulnerability of SMEs to flooding. This will be achieved by identifying major internal and external attributes explaining resilience capacity which is particularly important given the limited resources these enterprises have and that they tend to be primary sources of vulnerabilities in supply chain networks, generating Single Points of Failure (SPOF).

Keywords: Floods, Small & Medium-Sized enterprises, organizational resilience capacity, index development

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26 Post Liberal Perspective on Minorities Visibility in Contemporary Visual Culture: The Case of Mizrahi Jews

Authors: Merav Alush Levron, Sivan Rajuan Shtang

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From as early as their emergence in Europe and the US, postmodern and post-colonial paradigm have formed the backbone of the visual culture field of study. The self-representation project of political minorities is studied, described and explained within the premises and perspectives drawn from these paradigms, addressing the key issues they had raised: modernism’s crisis of representation. The struggle for self-representation, agency and multicultural visibility sought to challenge the liberal pretense of universality and equality, hitting at its different blind spots, on issues such as class, gender, race, sex, and nationality. This struggle yielded subversive identity and hybrid performances, including reclaiming, mimicry and masquerading. These performances sought to defy the uniform, universal self, which forms the basis for the liberal, rational, enlightened subject. The argument of this research runs that this politics of representation itself is confined within liberal thought. Alongside post-colonialism and multiculturalism’s contribution in undermining oppressive structures of power, generating diversity in cultural visibility, and exposing the failure of liberal colorblindness, this subversion is constituted in the visual field by way of confrontation, flying in the face of the universal law and relying on its ongoing comparison and attribution to this law. Relying on Deleuze and Guattari, this research set out to draw theoretic and empiric attention to an alternative, post-liberal occurrence which has been taking place in the visual field in parallel to the contra-hegemonic phase and as a product of political reality in the aftermath of the crisis of representation. It is no longer a counter-representation; rather, it is a motion of organic minor desire, progressing in the form of flows and generating what Deleuze and Guattari termed deterritorialization of social structures. This discussion shall have its focus on current post-liberal performances of ‘Mizrahim’ (Jewish Israelis of Arab and Muslim extraction) in the visual field in Israel. In television, video art and photography, these performances challenge the issue of representation and generate concrete peripheral Mizrahiness, realized in the visual organization of the photographic frame. Mizrahiness then transforms from ‘confrontational’ representation into a 'presence', flooding the visual sphere in our plain sight, in a process of 'becoming'. The Mizrahi desire is exerted on the plains of sound, spoken language, the body and the space where they appear. It removes from these plains the coding and stratification engendered by European dominance and rational, liberal enlightenment. This stratification, adhering to the hegemonic surface, is flooded not by way of resisting false consciousness or employing hybridity, but by way of the Mizrahi identity’s own productive, material immanent yearning. The Mizrahi desire reverberates with Mizrahi peripheral 'worlds of meaning', where post-colonial interpretation almost invariably identifies a product of internalized oppression, and a recurrence thereof, rather than a source in itself - an ‘offshoot, never a wellspring’, as Nissim Mizrachi clarifies in his recent pioneering work. The peripheral Mizrahi performance ‘unhook itself’, in Deleuze and Guattari words, from the point of subjectification and interpretation and does not correspond with the partialness, absence, and split that mark post-colonial identities.

Keywords: desire, minority, Mizrahi Jews, post-colonialism, post-liberalism, visibility, Deleuze and Guattari

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25 Linguistic Insights Improve Semantic Technology in Medical Research and Patient Self-Management Contexts

Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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24 Effect of Additives on Post-hydrogen Decompression Microstructure and Mechanical Behaviour of PA11 Involved in Type-IV Hydrogen Tank Liners

Authors: Mitia Ramarosaona, Sylvie Castagnet, Damien Halm, Henri-Alexandre Cayzac, Nicolas Dufaure, Philippe Papin

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In light of the ongoing energy transition, 'Infrastructure developments' for hydrogen transportation and storage raise studies on the materials employed for hyperbaric vessels. Type IV tanks represent the most mature choice for gaseous hydrogen storage at high pressure – 70MPa. These tanks are made of a composite shell and an internal hydrogen-exposed polymer liner. High pressure conditions lead to severe mechanical loading requiring high resistance. Liner is in contact with hydrogen and undergoes compression – decompression cycles during system filling and emptying. Stresses induced by this loading, coupled with hydrogen diffusion, were found to cause microstructural changes and degradation of mechanical behaviour after decompression phase in some studies on HDPE. These phenomena are similar to those observed in elastomeric components like sealing rings, which can affect permeability and lead to their failure. They may lead to a hydrogen leak, compromising security and tightness of the tank. While these phenomena have been identified in elastomers, they remain less addressed in thermoplastics and consequences post-decompression damages on mechanical behaviour and to the best of author's knowledge was not studied either. Different additives are also included in liner formulation to improve its behaviour. This study aimed to better understand damage micro-mechanisms in PA11s exposed to hydrogen compression-decompression cycles and understand if additives influence their resistance. Samples of pure, plasticized and impact-modified PA11s are exposed to 1, 3 and 8 pressure cycles including hydrogen saturation at 70MPa followed by severe 15-second decompression. After hydrogen exposure and significantly later than full desorption, the residual mechanical behaviour is characterized through impact and monotonic tensile tests, on plain and notched samples. Several techniques of microstructure and micro-nano damage characterization are carried out to assess whether changes in macroscopic properties are driven by microstructural changes in the crystalline structure (SAXS-WAXS acquisitions and SEM micrographs). Thanks to WAXS acquisition and microscopic observation, the effects due to additives and pressure consequences can be decorrelated. Pure PA11 and PA11 with a low percentage of additives show an increase in stress level at the first yielding point after hydrogen cycles. The amplitude of the stress increase is more important in formulation with additives because of changes in PA11 matrix behavior and environment created by additives actions. Plasticizer modifies chain mobility leading to microstructure changes while other additives, more ductile than PA11, is able to cavitate inside PA11 matrix when undergoing decompression. On plasticized formulation, plasticizer migration are suspected to enhance impact of hydrogen cycling on mechanical behaviour. Compared to the literature on HDPE and elastomers, no damages like cavitation or cracking could be evidenced from SAXS experiments on every PA11 formulation tested. In perspectives, on all formulation, experimental work is underway to confirm influence of residual pressure level after decompression on post-decompression damages level, the aim is to better understand the factors affecting the mechanical behavior of thermoplastics subject to mechanical solicitation from decompression in hydrogen tank liners, not mechanical behaviour of liner in hydrogen tanks directly.

Keywords: additives, hydrogen tank liner, microstructural analysis, PA11

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23 Kanga Traditional Costume as a Tool for Community Empowerment in Tanzania in Ubuntu perspective - A Literature Review

Authors: Meinrad Haule Lembuka

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Introduction: Ubuntu culture represents African humanism with collective and positive feeling of people living together, interdependence, equally and peaceful etc. Overtime, Ubuntu culture developed varieties of communicative strategies to express experiences, feelings and knowledge. Khanga or kanga (garment) is among the Ubuntu cultural practice of Bantu speaking people along the East African coast following interaction with Arabs and Bantu speaking people to formulate Swahili culture. Kanga or Kanga is a Swahili word which means a traditional soft cotton cloths in varieties of colours, patterns, and styles which as a deep cultural, historical, and social significance not only in Tanzania but the rest of East African coast. Swahili culture is a sub culture of Ubuntu African culture which is rich in customs and rituals that serve to preserve goodness and life where Tanzania, like the rest of East African societies along the Indian coast engaged in kanga dressing custom under Swahili culture to express their feelings and knowledge sharing. After the independence of Tanzania (formerly Tanganyika) from British colonial rule, Kanga traditional dressing gained momentum in Swahili culture and spread to the rest of East Africa and beyond. To date kanga dressing holds a good position as a formal and informal tool for advocating marginalised groups, counselling, psychosocial therapy, liberation, compassion, love, justice, campaign, and cerebration etc. Methodology: A literature review method was guided by Ubuntu theory to assess the implications of kanga traditional dressing in empowering Tanzanian community. Findings: During slavery, slaves wore Kaniki and people despised Kaniki dressing due to its association with slavery. Ex-slave women seeking to become part of the Swahili society began to decorate their Kaniki clothes. After slavery was abolished in 1897, Kangas began to be used for self-empowerment and to indicate that the wearer had personal wealth. During colonial era, freedom of expressions for Africans were restricted by colonial masters thus Tanzanians used kanga to express the evils of colonialism and other social problems, Under Ubuntu value of unity and solidarity liberation and independence fighters crafted motto and liberation messages that were shared and spread rapidly in the community. Political parities like TANU used kanga to spread nationalism and Ujamaa policy. kanga is more than a piece of fabric-it is a space for women to voice unspeakable communication and a women-centred repository for indigenous knowledge, feminisms addressing social ills, happiness, campaigns, memories and reconciliation etc. Kanga provides an indirect voice and support vulnerable and marginalised populations and strongly it has proved to be a peaceful platform of capture attention of government and societies. Kanga textiles gained increased international fame when an Obama kanga design was produced upon the president’s election in 2008 and his visit to Tanzania in 2013. Conclusion: Kanga preserves and symbolises Swahili culture and contributes in realization of social justice, inclusion, national identity and unity. As an inclusive cultural tool, Kanga spread across Africa to international community and the practice has moved from being a woman domination dressing code to other sex orientations.

Keywords: African culture, Kanga, khanga, swahili culture, ubuntu

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22 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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21 MusicTherapy for Actors: An Exploratory Study Applied to Students from University Theatre Faculty

Authors: Adriana De Serio, Adrian Korek

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Aims: This experiential research work presents a Group-MusicTherapy-Theatre-Plan (MusThePlan) the authors have carried out to support the actors. The MusicTherapy gives rise to individual psychophysical feedback and influences the emotional centres of the brain and the subconsciousness. Therefore, the authors underline the effectiveness of the preventive, educational, and training goals of the MusThePlan to lead theatre students and actors to deal with anxiety and to overcome psychophysical weaknesses, shyness, emotional stress in stage performances, to increase flexibility, awareness of one's identity and resources for a positive self-development and psychophysical health, to develop and strengthen social bonds, increasing a network of subjects working for social inclusion and reduction of stigma. Materials-Methods: Thirty students from the University Theatre Faculty participated in weekly music therapy sessions for two months; each session lasted 120 minutes. MusThePlan: Each session began with a free group rhythmic-sonorous-musical-production by body-percussion, voice-canto, instruments, to stimulate communication. Then, a synchronized-structured bodily-rhythmic-sonorous-musical production also involved acting, dances, movements of hands and arms, hearing, and more sensorial perceptions and speech to balance motor skills and the muscular tone. Each student could be the director-leader of the group indicating a story to inspire the group's musical production. The third step involved the students in rhythmic speech and singing drills and in vocal exercises focusing on the musical pitch to improve the intonation and on the diction to improve the articulation and lead up it to an increased intelligibility. At the end of each musictherapy session and of the two months, the Musictherapy Assessment Document was drawn up by analysis of observation protocols and two Indices by the authors: Patient-Environment-Music-Index (time to - tn) to estimate the behavior evolution, Somatic Pattern Index to monitor subject’s eye and mouth and limb motility, perspiration, before, during and after musictherapy sessions. Results: After the first month, the students (non musicians) learned to play percussion instruments and formed a musical band that played classical/modern music on the percussion instruments with the musictherapist/pianist/conductor in a public concert. At the end of the second month, the students performed a public musical theatre show, acting, dancing, singing, and playing percussion instruments. The students highlighted the importance of the playful aspects of the group musical production in order to achieve emotional contact and harmony within the group. The students said they had improved kinetic and vocal and all the skills useful for acting activity and the nourishment of the bodily and emotional balance. Conclusions: The MusThePlan makes use of some specific MusicTherapy methodological models, techniques, and strategies useful for the actors. The MusThePlan can destroy the individual "mask" and can be useful when the verbal language is unable to undermine the defense mechanisms of the subject. The MusThePlan improves actor’s psychophysical activation, motivation, gratification, knowledge of one's own possibilities, and the quality of life. Therefore, the MusThePlan could be useful to carry out targeted interventions for the actors with characteristics of repeatability, objectivity, and predictability of results. Furthermore, it would be useful to plan a University course/master in “MusicTherapy for the Theatre”.

Keywords: musictherapy, sonorous-musical energy, quality of life, theatre

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20 Increasing Student Engagement through Culturally-Responsive Classroom Management

Authors: Catherine P. Bradshaw, Elise T. Pas, Katrina J. Debnam, Jessika H. Bottiani, Michael Rosenberg

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Worldwide, ethnically and culturally diverse students are at increased risk for school failure, discipline problems, and dropout. Despite decades of concern about this issue of disparities in education and other fields (e.g., 'school to prison pipeline'), there has been limited empirical examination of models that can actually reduce these gaps in schools. Moreover, few studies have examined the effectiveness of in-service teacher interventions and supports specifically designed to reduce discipline disparities and improve student engagement. This session provides an overview of the evidence-based Double Check model which serves as a framework for teachers to use culturally-responsive strategies to engage ethnically and culturally diverse students in the classroom and reduce discipline problems. Specifically, Double Check is a school-based prevention program which includes three core components: (a) enhancements to the school-wide Positive Behavioral Interventions and Supports (PBIS) tier-1 level of support; (b) five one-hour professional development training sessions, each of which addresses five domains of cultural competence (i.e., connection to the curriculum, authentic relationships, reflective thinking, effective communication, and sensitivity to students’ culture); and (c) coaching of classroom teachers using an adapted version of the Classroom Check-Up, which intends to increase teachers’ use of effective classroom management and culturally-responsive strategies using research-based motivational interviewing and data-informed problem-solving approaches. This paper presents findings from a randomized controlled trial (RCT) testing the impact of Double Check, on office discipline referrals (disaggregated by race) and independently observed and self-reported culturally-responsive practices and classroom behavior management. The RCT included 12 elementary and middle schools; 159 classroom teachers were randomized either to receive coaching or serve as comparisons. Specifically, multilevel analyses indicated that teacher self-reported culturally responsive behavior management improved over the course of the school year for teachers who received the coaching and professional development. However, the average annual office discipline referrals issued to black students were reduced among teachers who were randomly assigned to receive coaching relative to comparison teachers. Similarly, observations conducted by trained external raters indicated significantly more teacher proactive behavior management and anticipation of student problems, higher student compliance, less student non-compliance, and less socially disruptive behaviors in classrooms led by coached teachers than classrooms led teachers randomly assigned to the non-coached condition. These findings indicated promising effects of the Double Check model on a range of teacher and student outcomes, including disproportionality in office discipline referrals among Black students. These results also suggest that the Double Check model is one of only a few systematic approaches to promoting culturally-responsive behavior management which has been rigorously tested and shown to be associated with improvements in either student or staff outcomes indicated significant reductions in discipline problems and improvements in behavior management. Implications of these findings are considered within the broader context of globalization and demographic shifts, and their impacts on schools. These issues are particularly timely, given growing concerns about immigration policies in the U.S. and abroad.

Keywords: ethnically and culturally diverse students, student engagement, school-based prevention, academic achievement

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19 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

Abstract:

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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18 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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17 Delivering Safer Clinical Trials; Using Electronic Healthcare Records (EHR) to Monitor, Detect and Report Adverse Events in Clinical Trials

Authors: Claire Williams

Abstract:

Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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16 Evaluation of Functional Properties of Protein Hydrolysate from the Fresh Water Mussel Lamellidens marginalis for Nutraceutical Therapy

Authors: Jana Chakrabarti, Madhushrita Das, Ankhi Haldar, Roshni Chatterjee, Tanmoy Dey, Pubali Dhar

Abstract:

High incidences of Protein Energy Malnutrition as a consequence of low protein intake are quite prevalent among the children in developing countries. Thus prevention of under-nutrition has emerged as a critical challenge to India’s developmental Planners in recent times. Increase in population over the last decade has led to greater pressure on the existing animal protein sources. But these resources are currently declining due to persistent drought, diseases, natural disasters, high-cost of feed, and low productivity of local breeds and this decline in productivity is most evident in some developing countries. So the need of the hour is to search for efficient utilization of unconventional low-cost animal protein resources. Molluscs, as a group is regarded as under-exploited source of health-benefit molecules. Bivalve is the second largest class of phylum Mollusca. Annual harvests of bivalves for human consumption represent about 5% by weight of the total world harvest of aquatic resources. The freshwater mussel Lamellidens marginalis is widely distributed in ponds and large bodies of perennial waters in the Indian sub-continent and well accepted as food all over India. Moreover, ethno-medicinal uses of the flesh of Lamellidens among the rural people to treat hypertension have been documented. Present investigation thus attempts to evaluate the potential of Lamellidens marginalis as functional food. Mussels were collected from freshwater ponds and brought to the laboratory two days before experimentation for acclimatization in laboratory conditions. Shells were removed and fleshes were preserved at- 20oC until analysis. Tissue homogenate was prepared for proximate studies. Fatty acids and amino acids composition were analyzed. Vitamins, Minerals and Heavy metal contents were also studied. Mussel Protein hydrolysate was prepared using Alcalase 2.4 L and degree of hydrolysis was evaluated to analyze its Functional properties. Ferric Reducing Antioxidant Power (FRAP) and DPPH Antioxidant assays were performed. Anti-hypertensive property was evaluated by measuring Angiotensin Converting Enzyme (ACE) inhibition assay. Proximate analysis indicates that mussel meat contains moderate amount of protein (8.30±0.67%), carbohydrate (8.01±0.38%) and reducing sugar (4.75±0.07%), but less amount of fat (1.02±0.20%). Moisture content is quite high but ash content is very low. Phospholipid content is significantly high (19.43 %). Lipid constitutes, substantial amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which have proven prophylactic values. Trace elements are found present in substantial amount. Comparative study of proximate nutrients between Labeo rohita, Lamellidens and cow’s milk indicates that mussel meat can be used as complementary food source. Functionality analyses of protein hydrolysate show increase in Fat absorption, Emulsification, Foaming capacity and Protein solubility. Progressive anti-oxidant and anti-hypertensive properties have also been documented. Lamellidens marginalis can thus be regarded as a functional food source as this may combine effectively with other food components for providing essential elements to the body. Moreover, mussel protein hydrolysate provides opportunities for utilizing it in various food formulations and pharmaceuticals. The observations presented herein should be viewed as a prelude to what future holds.

Keywords: functional food, functional properties, Lamellidens marginalis, protein hydrolysate

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15 Burkholderia Cepacia ST 767 Causing a Three Years Nosocomial Outbreak in a Hemodialysis Unit

Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

Abstract:

Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

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14 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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13 Social Enterprises over Microfinance Institutions: The Challenges of Governance and Management

Authors: Dean Sinković, Tea Golja, Morena Paulišić

Abstract:

Upon the end of the vicious war in former Yugoslavia in 1995, international development community widely promoted microfinance as the key development framework to eradicate poverty, create jobs, increase income. Widespread claims were made that microfinance institutions would play vital role in creating a bedrock for sustainable ‘bottom-up’ economic development trajectory, thus, helping newly formed states to find proper way from economic post-war depression. This uplifting neoliberal narrative has no empirical support in the Republic of Croatia. Firstly, the type of enterprises created via microfinance sector are small, unskilled, labor intensive, no technology and with huge debt burden. This results in extremely high failure rates of microenterprises and poor individuals plunging into even deeper poverty, acute indebtedness and social marginalization. Secondly, evidence shows that microcredit is exact reflection of dangerous and destructive sub-prime lending model with ‘boom-to-bust’ scenarios in which benefits are solely extracted by the tiny financial and political elite working around the microfinance sector. We argue that microcredit providers are not proper financial structures through which developing countries should look way out of underdevelopment and poverty. In order to achieve sustainable long-term growth goals, public policy needs to focus on creating, supporting and facilitating the small and mid-size enterprises development. These enterprises should be technically sophisticated, capable of creating new capabilities and innovations, with managerial expertise (skills formation) and inter-connected with other organizations (i.e. clusters, networks, supply chains, etc.). Evidence from South-East Europe suggest that such structures are not created via microfinance model but can be fostered through various forms of social enterprises. Various legal entities may operate as social enterprises: limited liability private company, limited liability public company, cooperative, associations, foundations, institutions, Mutual Insurances and Credit union. Our main hypothesis is that cooperatives are potential agents of social and economic transformation and community development in the region. Financial cooperatives are structures that can foster more efficient allocation of financial resources involving deeper democratic arrangements and more socially just outcomes. In Croatia, pioneers of the first social enterprises were civil society organizations whilst forming a separated legal entity. (i.e. cooperatives, associations, commercial companies working on the principles of returning the investment to the founder). Ever since 1995 cooperatives in Croatia have not grown by pursuing their own internal growth but mostly by relying on external financial support. The greater part of today’s registered cooperatives tend to be agricultural (39%), followed by war veterans cooperatives (38%) and others. There are no financial cooperatives in Croatia. Due to the above mentioned we look at the historical developments and the prevailing social enterprises forms and discuss their advantages and disadvantages as potential agents for social and economic transformation and community development in the region. There is an evident lack of understanding of this business model and of its potential for social and economic development followed by an unfavorable institutional environment. Thus, we discuss the role of governance and management in the formation of social enterprises in Croatia, stressing the challenges for the governance of the country’s social enterprise movement.

Keywords: financial cooperatives, governance and management models, microfinance institutions, social enterprises

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12 A Prospective Neurosurgical Registry Evaluating the Clinical Care of Traumatic Brain Injury Patients Presenting to Mulago National Referral Hospital in Uganda

Authors: Benjamin J. Kuo, Silvia D. Vaca, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Lydia Nanjula, Christine Muhumuza, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

Abstract:

Background: Traumatic Brain Injury (TBI) is disproportionally concentrated in low- and middle-income countries (LMICs), with the odds of dying from TBI in Uganda more than 4 times higher than in high income countries (HICs). The disparities in the injury incidence and outcome between LMICs and resource-rich settings have led to increased health outcomes research for TBIs and their associated risk factors in LMICs. While there have been increasing TBI studies in LMICs over the last decade, there is still a need for more robust prospective registries. In Uganda, a trauma registry implemented in 2004 at the Mulago National Referral Hospital (MNRH) showed that RTI is the major contributor (60%) of overall mortality in the casualty department. While the prior registry provides information on injury incidence and burden, it’s limited in scope and doesn’t follow patients longitudinally throughout their hospital stay nor does it focus specifically on TBIs. And although these retrospective analyses are helpful for benchmarking TBI outcomes, they make it hard to identify specific quality improvement initiatives. The relationship among epidemiology, patient risk factors, clinical care, and TBI outcomes are still relatively unknown at MNRH. Objective: The objectives of this study are to describe the processes of care and determine risk factors predictive of poor outcomes for TBI patients presenting to a single tertiary hospital in Uganda. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Research Electronic Data Capture (REDCap) was used to systematically collect variables spanning 8 categories. Univariate and multivariate analysis were conducted to determine significant predictors of mortality. Results: 563 TBI patients were enrolled from 1 June – 30 November 2016. 102 patients (18%) received surgery, 29 patients (5.1%) intended for surgery failed to receive it, and 251 patients (45%) received non-operative management. Overall mortality was 9.6%, which ranged from 4.7% for mild and moderate TBI to 55% for severe TBI patients with GCS 3-5. Within each TBI severity category, mortality differed by management pathway. Variables predictive of mortality were TBI severity, more than one intracranial bleed, failure to receive surgery, high dependency unit admission, ventilator support outside of surgery, and hospital arrival delayed by more than 4 hours. Conclusions: The overall mortality rate of 9.6% in Uganda for TBI is high, and likely underestimates the true TBI mortality. Furthermore, the wide-ranging mortality (3-82%), high ICU fatality, and negative impact of care delays suggest shortcomings with the current triaging practices. Lack of surgical intervention when needed was highly predictive of mortality in TBI patients. Further research into the determinants of surgical interventions, quality of step-up care, and prolonged care delays are needed to better understand the complex interplay of variables that affect patient outcome. These insights guide the development of future interventions and resource allocation to improve patient outcomes.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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11 Risks for Cyanobacteria Harmful Algal Blooms in Georgia Piedmont Waterbodies Due to Land Management and Climate Interactions

Authors: Sam Weber, Deepak Mishra, Susan Wilde, Elizabeth Kramer

Abstract:

The frequency and severity of cyanobacteria harmful blooms (CyanoHABs) have been increasing over time, with point and non-point source eutrophication and shifting climate paradigms being blamed as the primary culprits. Excessive nutrients, warm temperatures, quiescent water, and heavy and less regular rainfall create more conducive environments for CyanoHABs. CyanoHABs have the potential to produce a spectrum of toxins that cause gastrointestinal stress, organ failure, and even death in humans and animals. To promote enhanced, proactive CyanoHAB management, risk modeling using geospatial tools can act as predictive mechanisms to supplement current CyanoHAB monitoring, management and mitigation efforts. The risk maps would empower water managers to focus their efforts on high risk water bodies in an attempt to prevent CyanoHABs before they occur, and/or more diligently observe those waterbodies. For this research, exploratory spatial data analysis techniques were used to identify the strongest predicators for CyanoHAB blooms based on remote sensing-derived cyanobacteria cell density values for 771 waterbodies in the Georgia Piedmont and landscape characteristics of their watersheds. In-situ datasets for cyanobacteria cell density, nutrients, temperature, and rainfall patterns are not widely available, so free gridded geospatial datasets were used as proxy variables for assessing CyanoHAB risk. For example, the percent of a watershed that is agriculture was used as a proxy for nutrient loading, and the summer precipitation within a watershed was used as a proxy for water quiescence. Cyanobacteria cell density values were calculated using atmospherically corrected images from the European Space Agency’s Sentinel-2A satellite and multispectral instrument sensor at a 10-meter ground resolution. Seventeen explanatory variables were calculated for each watershed utilizing the multi-petabyte geospatial catalogs available within the Google Earth Engine cloud computing interface. The seventeen variables were then used in a multiple linear regression model, and the strongest predictors of cyanobacteria cell density were selected for the final regression model. The seventeen explanatory variables included land cover composition, winter and summer temperature and precipitation data, topographic derivatives, vegetation index anomalies, and soil characteristics. Watershed maximum summer temperature, percent agriculture, percent forest, percent impervious, and waterbody area emerged as the strongest predictors of cyanobacteria cell density with an adjusted R-squared value of 0.31 and a p-value ~ 0. The final regression equation was used to make a normalized cyanobacteria cell density index, and a Jenks Natural Break classification was used to assign waterbodies designations of low, medium, or high risk. Of the 771 waterbodies, 24.38% were low risk, 37.35% were medium risk, and 38.26% were high risk. This study showed that there are significant relationships between free geospatial datasets representing summer maximum temperatures, nutrient loading associated with land use and land cover, and the area of a waterbody with cyanobacteria cell density. This data analytics approach to CyanoHAB risk assessment corroborated the literature-established environmental triggers for CyanoHABs, and presents a novel approach for CyanoHAB risk mapping in waterbodies across the greater southeastern United States.

Keywords: cyanobacteria, land use/land cover, remote sensing, risk mapping

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10 Adequate Nutritional Support and Monitoring in Post-Traumatic High Output Duodenal Fistula

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

Abstract:

Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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9 Large-scale GWAS Investigating Genetic Contributions to Queerness Will Decrease Stigma Against LGBTQ+ Communities

Authors: Paul J. McKay

Abstract:

Large-scale genome-wide association studies (GWAS) investigating genetic contributions to sexual orientation and gender identity are largely lacking and may reduce stigma experienced in the LGBTQ+ community by providing an underlying biological explanation for queerness. While there is a growing consensus within the scientific community that genetic makeup contributes – at least in part – to sexual orientation and gender identity, there is a marked lack of genomics research exploring polygenic contributions to queerness. Based on recent (2019) findings from a large-scale GWAS investigating the genetic architecture of same-sex sexual behavior, and various additional peer-reviewed publications detailing novel insights into the molecular mechanisms of sexual orientation and gender identity, we hypothesize that sexual orientation and gender identity are complex, multifactorial, and polygenic; meaning that many genetic factors contribute to these phenomena, and environmental factors play a possible role through epigenetic modulation. In recent years, large-scale GWAS studies have been paramount to our modern understanding of many other complex human traits, such as in the case of autism spectrum disorder (ASD). Despite possible benefits of such research, including reduced stigma towards queer people, improved outcomes for LGBTQ+ in familial, socio-cultural, and political contexts, and improved access to healthcare (particularly for trans populations); important risks and considerations remain surrounding this type of research. To mitigate possibilities such as invalidation of the queer identities of existing LGBTQ+ individuals, genetic discrimination, or the possibility of euthanasia of embryos with a genetic predisposition to queerness (through reproductive technologies like IVF and/or gene-editing in utero), we propose a community-engaged research (CER) framework which emphasizes the privacy and confidentiality of research participants. Importantly, the historical legacy of scientific research attempting to pathologize queerness (in particular, falsely equating gender variance to mental illness) must be acknowledged to ensure any future research conducted in this realm does not propagate notions of homophobia, transphobia or stigma against queer people. Ultimately, in a world where same-sex sexual activity is criminalized in 69 UN member states, with 67 of these states imposing imprisonment, 8 imposing public flogging, 6 (Brunei, Iran, Mauritania, Nigeria, Saudi Arabia, Yemen) invoking the death penalty, and another 5 (Afghanistan, Pakistan, Qatar, Somalia, United Arab Emirates) possibly invoking the death penalty, the importance of this research cannot be understated, as finding a biological basis for queerness would directly oppose the harmful rhetoric that “being LGBTQ+ is a choice.” Anti-trans legislation is similarly widespread: In the United States in 2022 alone (as of Oct. 13), 155 anti-trans bills have been introduced preventing trans girls and women from playing on female sports teams, barring trans youth from using bathrooms and locker rooms that align with their gender identity, banning access to gender affirming medical care (e.g., hormone-replacement therapy, gender-affirming surgeries), and imposing legal restrictions on name changes. Understanding that a general lack of knowledge about the biological basis of queerness may be a contributing factor to the societal stigma faced by gender and sexual orientation minorities, we propose the initiation of large-scale GWAS studies investigating the genetic basis of gender identity and sexual orientation.

Keywords: genome-wide association studies (GWAS), sexual and gender minorities (SGM), polygenicity, community-engaged research (CER)

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8 Development of a Core Set of Clinical Indicators to Measure Quality of Care for Thyroid Cancer: A Modified-Delphi Approach

Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

Abstract:

BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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7 Highly Robust Crosslinked BIAN-based Binder to Stabilize High-Performance Silicon Anode in Lithium-Ion Secondary Battery

Authors: Agman Gupta, Rajashekar Badam, Noriyoshi Matsumi

Abstract:

Introduction: Recently, silicon has been recognized as one of the potential alternatives as anode active material in Li-ion batteries (LIBs) to replace the conventionally used graphite anodes. Silicon is abundantly present in the nature, it can alloy with lithium metal, and has a higher theoretical capacity (~4200 mAhg-1) that is approximately 10 times higher than graphite. However, because of a large volume expansion (~400%) upon repeated de-/alloying, the pulverization of Si particles causes the exfoliation of electrode laminate leading to the loss of electrical contact and adversely affecting the formation of solid-electrolyte interface (SEI).1 Functional polymers as binders have emerged as a competitive strategy to mitigate these drawbacks and failure mechanism of silicon anodes.1 A variety of aqueous/non-aqueous polymer binders like sodium carboxy-methyl cellulose (CMC-Na), styrene butadiene rubber (SBR), poly(acrylic acid), and other variants like mussel inspired binders have been investigated to overcome these drawbacks.1 However, there are only a few reports that mention the attempt of addressing all the drawbacks associated with silicon anodes effectively using a single novel functional polymer system as a binder. In this regard, here, we report a novel highly robust n-type bisiminoacenaphthenequinone (BIAN)-paraphenylene-based crosslinked polymer as a binder for Si anodes in lithium-ion batteries (Fig. 1). On its application, crosslinked-BIAN binder was evaluated to provide mechanical robustness to the large volume expansion of Si particles, maintain electrical conductivity within the electrode laminate, and facilitate in the formation of a thin SEI by restricting the extent of electrolyte decomposition on the surface of anode. The fabricated anodic half-cells were evaluated electrochemically for their rate capability, cyclability, and discharge capacity. Experimental: The polymerized BIAN (P-BIAN) copolymer was synthesized as per the procedure reported by our group.2 The synthesis of crosslinked P-BIAN: a solution of P-BIAN copolymer (1.497 g, 10 mmol) in N-methylpyrrolidone (NMP) (150 ml) was set-up to stir under reflux in nitrogen atmosphere. To this, 1,6-dibromohexane (5 mmol, 0.77 ml) was added dropwise. The resultant reaction mixture was stirred and refluxed at 150 °C for 24 hours followed by refrigeration for 3 hours at 5 °C. The product was obtained by evaporating the NMP solvent under reduced pressure and drying under vacuum at 120 °C for 12 hours. The obtained product was a black colored sticky compound. It was characterized by 1H-NMR, XPS, and FT-IR techniques. Results and Discussion: The N 1s XPS spectrum of the crosslinked BIAN polymer showed two characteristic peaks corresponding to the sp2 hybridized nitrogen (-C=N-) at 399.6 eV of the diimine backbone in the BP and quaternary nitrogen at 400.7 eV corresponding to the crosslinking of BP via dibromohexane. The DFT evaluation of the crosslinked BIAN binder showed that it has a low lying lowest unoccupied molecular orbital (LUMO) that enables it to get doped in the reducing environment and influence the formation of a thin (SEI). Therefore, due to the mechanically robust crosslinked matrices as well as its influence on the formation of a thin SEI, the crosslinked BIAN binder stabilized the Si anode-based half-cell for over 1000 cycles with a reversible capacity of ~2500 mAhg-1 and ~99% capacity retention as shown in Fig. 2. The dynamic electrochemical impedance spectroscopy (DEIS) characterization of crosslinked BIAN-based anodic half-cell confirmed that the SEI formed was thin in comparison with the conventional binder-based anodes. Acknowledgement: We are thankful to the financial support provided by JST-Mirai Program, Grant Number: JP18077239

Keywords: self-healing binder, n-type binder, thin solid-electrolyte interphase (SEI), high-capacity silicon anodes, low-LUMO

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6 Inhibitory Effects of Crocin from Crocus sativus L. on Cell Proliferation of a Medulloblastoma Human Cell Line

Authors: Kyriaki Hatziagapiou, Eleni Kakouri, Konstantinos Bethanis, Alexandra Nikola, Eleni Koniari, Charalabos Kanakis, Elias Christoforides, George Lambrou, Petros Tarantilis

Abstract:

Medulloblastoma is a highly invasive tumour, as it tends to disseminate throughout the central nervous system early in its course. Despite the high 5-year-survival rate, a significant number of patients demonstrate serious long- or short-term sequelae (e.g., myelosuppression, endocrine dysfunction, cardiotoxicity, neurological deficits and cognitive impairment) and higher mortality rates, unrelated to the initial malignancy itself but rather to the aggressive treatment. A strong rationale exists for the use of Crocus sativus L (saffron) and its bioactive constituents (crocin, crocetin, safranal) as pharmaceutical agents, as they exert significant health-promoting properties. Crocins are water soluble carotenoids. Unlike other carotenoids, crocins are highly water-soluble compounds, with relatively low toxicity as they are not stored in adipose and liver tissues. Crocins have attracted wide attention as promising anti-cancer agents, due to their antioxidant, anti-inflammatory, and immunomodulatory effects, interference with transduction pathways implicated in tumorigenesis, angiogenesis, and metastasis (disruption of mitotic spindle assembly, inhibition of DNA topoisomerases, cell-cycle arrest, apoptosis or cell differentiation) and sensitization of cancer cells to radiotherapy and chemotherapy. The current research aimed to study the potential cytotoxic effect of crocins on TE671 medulloblastoma cell line, which may be useful in the optimization of existing and development of new therapeutic strategies. Crocins were extracted from stigmas of saffron in ultrasonic bath, using petroleum-ether, diethylether and methanol 70%v/v as solvents and the final extract was lyophilized. Identification of crocins according to high-performance liquid chromatography (HPLC) analysis was determined comparing the UV-vis spectra and the retention time (tR) of the peaks with literature data. For the biological assays crocin was diluted to nuclease and protease free water. TE671 cells were incubated with a range of concentrations of crocins (16, 8, 4, 2, 1, 0.5 and 0.25 mg/ml) for 24, 48, 72 and 96 hours. Analysis of cell viability after incubation with crocins was performed with Alamar Blue viability assay. The active ingredient of Alamar Blue, resazurin, is a blue, nontoxic, cell permeable compound virtually nonfluorescent. Upon entering cells, resazurin is reduced to a pink and fluorescent molecule, resorufin. Viable cells continuously convert resazurin to resorufin, generating a quantitative measure of viability. The colour of resorufin was quantified by measuring the absorbance of the solution at 600 nm with a spectrophotometer. HPLC analysis indicated that the most abundant crocins in our extract were trans-crocin-4 and trans-crocin-3. Crocins exerted significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72 and 96 hours versus cells not exposed); as their concentration and time of exposure increased, the reduction of resazurin to resofurin decreased, indicating reduction in cell viability. IC50 values for each time point were calculated ~3.738, 1.725, 0.878 and 0.7566 mg/ml at 24, 48, 72 and 96 hours, respectively. The results of our study could afford the basis of research regarding the use of natural carotenoids as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgements: The research was funded by Fellowships of Excellence for Postgraduate Studies IKY-Siemens Programme.

Keywords: crocetin, crocin, medulloblastoma, saffron

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5 Investigation of Delamination Process in Adhesively Bonded Hardwood Elements under Changing Environmental Conditions

Authors: M. M. Hassani, S. Ammann, F. K. Wittel, P. Niemz, H. J. Herrmann

Abstract:

Application of engineered wood, especially in the form of glued-laminated timbers has increased significantly. Recent progress in plywood made of high strength and high stiffness hardwoods, like European beech, gives designers in general more freedom by increased dimensional stability and load-bearing capacity. However, the strong hygric dependence of basically all mechanical properties renders many innovative ideas futile. The tendency of hardwood for higher moisture sorption and swelling coefficients lead to significant residual stresses in glued-laminated configurations, cross-laminated patterns in particular. These stress fields cause initiation and evolution of cracks in the bond-lines resulting in: interfacial de-bonding, loss of structural integrity, and reduction of load-carrying capacity. Subsequently, delamination of glued-laminated timbers made of hardwood elements can be considered as the dominant failure mechanism in such composite elements. In addition, long-term creep and mechano-sorption under changing environmental conditions lead to loss of stiffness and can amplify delamination growth over the lifetime of a structure even after decades. In this study we investigate the delamination process of adhesively bonded hardwood (European beech) elements subjected to changing climatic conditions. To gain further insight into the long-term performance of adhesively bonded elements during the design phase of new products, the development and verification of an authentic moisture-dependent constitutive model for various species is of great significance. Since up to now, a comprehensive moisture-dependent rheological model comprising all possibly emerging deformation mechanisms was missing, a 3D orthotropic elasto-plastic, visco-elastic, mechano-sorptive material model for wood, with all material constants being defined as a function of moisture content, was developed. Apart from the solid wood adherends, adhesive layer also plays a crucial role in the generation and distribution of the interfacial stresses. Adhesive substance can be treated as a continuum layer constructed from finite elements, represented as a homogeneous and isotropic material. To obtain a realistic assessment on the mechanical performance of the adhesive layer and a detailed look at the interfacial stress distributions, a generic constitutive model including all potentially activated deformation modes, namely elastic, plastic, and visco-elastic creep was developed. We focused our studies on the three most common adhesive systems for structural timber engineering: one-component polyurethane adhesive (PUR), melamine-urea-formaldehyde (MUF), and phenol-resorcinol-formaldehyde (PRF). The corresponding numerical integration approaches, with additive decomposition of the total strain are implemented within the ABAQUS FEM environment by means of user subroutine UMAT. To predict the true stress state, we perform a history dependent sequential moisture-stress analysis using the developed material models for both wood substrate and adhesive layer. Prediction of the delamination process is founded on the fracture mechanical properties of the adhesive bond-line, measured under different levels of moisture content and application of the cohesive interface elements. Finally, we compare the numerical predictions with the experimental observations of de-bonding in glued-laminated samples under changing environmental conditions.

Keywords: engineered wood, adhesive, material model, FEM analysis, fracture mechanics, delamination

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4 Developing a Framework for Sustainable Social Housing Delivery in Greater Port Harcourt City Rivers State, Nigeria

Authors: Enwin Anthony Dornubari, Visigah Kpobari Peter

Abstract:

This research has developed a framework for the provision of sustainable and affordable housing to accommodate the low-income population of Greater Port Harcourt City. The objectives of this study among others, were to: examine UN-Habitat guidelines for acceptable and sustainable social housing provision, describe past efforts of the Rivers State Government and the Federal Government of Nigeria to provide housing for the poor in the Greater Port Harcourt City area; obtain a profile of prospective beneficiaries of the social housing proposed by this research as well as perceptions of their present living conditions, and living in the proposed self-sustaining social housing development, based on the initial simulation of the proposal; describe the nature of the framework, guideline and management of the proposed social housing development and explain the modalities for its implementation. The study utilized the mixed methods research approach, aimed at triangulating findings from the quantitative and qualitative paradigms. Opinions of professional of the built environment; Director, Development Control, Greater Port Harcourt City Development Authority; Directors of Ministry of Urban Development and Physical Planning; Housing and Property Development Authority and managers of selected Primary Mortgage Institutions were sought and analyzed. There were four target populations for the study, namely: members of occupational sub-groups for FGDs (Focused Group Discussions); development professionals for KIIs (Key Informant Interviews), household heads in selected communities of GPHC; and relevant public officials for IDI (Individual Depth Interview). Focus Group Discussions (FGDs) were held with members of occupational sub-groups in each of the eight selected communities (Fisherfolk). The table shows that there were forty (40) members across all occupational sub-groups in each selected community, yielding a total of 320 in the eight (8) communities of Mgbundukwu (Mile 2 Diobu), Rumuodomaya, Abara (Etche), Igwuruta-Ali(Ikwerre), Wakama(Ogu-Bolo), Okujagu (Okrika), Akpajo (Eleme), and Okoloma (Oyigbo). For key informant interviews, two (2) members were judgmentally selected from each of the following development professions: urban and regional planners; architects; estate surveyors; land surveyors; quantity surveyors; and engineers. Concerning Population 3-Household Heads in Selected Communities of GPHC, a stratified multi-stage sampling procedure was adopted: Stage 1-Obtaining a 10% (a priori decision) sample of the component communities of GPHC in each stratum. The number in each stratum was rounded to one whole number to ensure representation of each stratum. Stage 2-Obtaining the number of households to be studied after applying the Taro Yamane formula, which aided in determining the appropriate number of cases to be studied at the precision level of 5%. Findings revealed, amongst others, that poor implementation of the UN-Habitat global shelter strategy, lack of stakeholder engagement, inappropriate locations, undue bureaucracy, lack of housing fairness and equity and high cost of land and building materials were the reasons for the failure of past efforts towards social housing provision in the Greater Port Harcourt City area. The study recommended a public-private partnership approach for the implementation and management of the framework. It also recommended a robust and sustained relationship between the management of the framework and the UN-Habitat office and other relevant government agencies responsible for housing development and all investment partners to create trust and efficiency.

Keywords: development, framework, low-income, sustainable, social housing

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3 Remote Building: An Integrated Approach to Domestic Rainwater Harvesting System Implementation in a Rural Village in Himachal Pradesh, India

Authors: Medha Iyer, Anshul Paul, Aunnesha Bhowmick, Anahita Banerjee, Sana Prasad, Anoushka Singal, Lauren Sinopoli, Pooja Bapat, Shivi Jain

Abstract:

In Himachal Pradesh, India, a majority of the population lives in rural villages spread throughout its hilly regions; many of these households rely on subsistence farming as their main source of livelihood. The student-run non-profit organization affiliated with this study, Project RISHI (Rural India Social and Health Improvement), works to promote sustainable development practices in Bharog Baneri, a gram panchayat, or union, of villages in Himachal Pradesh. In 2017, an established rainwater harvesting (RWH) project group within Project RISHI had surveyed many families, finding that the most common issue regarding food and water access was a lack of accessible water sources for agricultural use in the dry season. After a prototype build in 2018, the group built 6 systems for eligible residents that demonstrated need in 2019. Subsequently, the project went through an evaluation period, including self-evaluation of project goals and post-impact surveying of system recipients. The group used the social impact assessment model to optimize the implementation of domestic RWH systems in Bharog Baneri. Assessing implementation after in-person builds produced three pillars of focus — system design, equitable recipient selection, and community involvement. After two years of remote involvement during COVID-19, the group prepared to visit Bharog Baneri to build 10 new systems in the Summer 2022. First, the group created a more durable and cost-effective design that could withstand debris and heavy rains to prevent gutter failure. The domestic system design is a rooftop RWH catchment system with two tanks attached, an overflow pipe, debris filtration, and a spigot for accessibility. The group also developed a needs-based eligibility methodology with assistance from village leaders and surveying in Bharog Baneri and set up the groundwork for a future community board. COVID-19 has strengthened remote work, telecommunications, and other organizational support systems. As sustainable development evolves to encompass these practices in a post-pandemic world, the potential for new RWH system design and implementation processes has emerged as well. This raises the question: how can a social impact assessment of rural RWH projects inform an integrated approach to post-pandemic RWH system practices? The objective of this exploratory study is to investigate and evaluate a novel remote build infrastructure that brings access to reliable and sustainable sources of water for agricultural use. To construct the remote build approach, the group identified and assigned a point of contact who was experienced with previous RWH system builds. The recipients were selected based on demonstrated need and ease of building. The contact visited each of the houses and coordinated supplier relations and transportation of the materials in accordance with the participatory approach to sustainable development. Over the course of two months, the group completed four system builds with the resulting infrastructure. The infrastructure adhered to the social impact assessment model by centering supplier relations, material transportation, and construction logistics within the community. The conclusion of this exploration is that post-pandemic rural RWH practices should be rooted in strengthening villager communication and utilizing local assets. Through this, non-profit organizations can incorporate remote build strategies into their long-term goals.

Keywords: capturing run-off from rooftops, domestic rainwater harvesting, Implementation approaches and strategies, rainwater harvesting and management in rural sectors

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2 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 59
1 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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