Search results for: arithmetic progression

Authors: Raudone Lina, Raudonis Raimondas, Liaudanskas Mindaugas, Pukalskas Audrius, Viskelis Pranas, Janulis Valdimaras

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Human health fortification, its protection and disease prophylaxis are the main problems of the health care systems. Plant origin materials and their preparations are applied for the prevention of the common diseases. Oxidative stress takes part in the pathogenesis of many autoimmune, neurodegenerative, tumor and ageing processes. The antioxidants are able to protect the human body from the free radicals and to stop the progression of numerous chronic diseases. The research of plant origin materials is relevant for the search of natural antioxidants. A group of compounds that gained scientific attention due to antioxidant properties and effects on human health are phenolic compounds. Phenolic compounds are widely abundant in various parts of plants, i.e. leaves, stems, roots, flowers and fruits. Most commonly consumed fruits all over the world are apples. It is very important to analyze the antioxidant activity of apples as they are extensively used in the prevention of various diseases. The aim of this study was to determine the antioxidant profiles of Malus domestica Borkh fruit cultivars (Aldas, Auksis, Connel Red, Ligol, Lodel, Rajka) and to identify the phenolic compounds with potent contribution to antioxidant activity. Nineteen constituents were identified in apple cultivars using ultra high performance liquid chromatography coupled to quadruple and time-of-flight mass spectrometers (UPLC–QTOF–MS). Phytochemical profile was constituted of phenolic acids, procyanidins, quercetin derivatives and dihydrochalcones. Reducing and radical scavenging activities of individual constituents were determined using high performance liquid chromatography (HPLC) coupled to post-column FRAP and ABTS assay, respectively. Significant differences of total radical scavenging and reducing activity (expressed as trolox equivalents, TE µmol/g) were determined between the investigated cultivars. Chlorogenic acid and complex of procyanidins were the main contributors to antioxidant activity determining up to 35 % and 55 % of total TE values, respectively. Determined phenolic composition and antioxidant activity significantly depend on apple cultivars. It is important to determine the individual compounds that are significant for antioxidant activity and that could be investigated in vivo systems. The identification of the antioxidants provides information for the further research of standardized extracts that could be used for pharmaceutical preparations with specific phenolic traits.

Keywords: FRAP, ABTS, antioxidant, phenolic, apples, chlorogenic acid

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Authors: CA Kishore S. Peshori

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Introduction: India, a country with vast diversity and huge population is going to have largest young population by 2020. Higher education has and will always be the basic requirement for making a developing nation to a developed nation. To improve any system it needs to be bench-marked. There have been various tools for bench-marking the systems. Education is delivered in India by universities which are mainly funded by government. This universities for delivering the education sets up colleges which are again funded mainly by government. Recently however there has also been autonomy given to universities and colleges. Moreover foreign universities are waiting to enter Indian boundaries. With a large number of universities and colleges it has become more and more necessary to measure this institutes for bench-marking. There have been various tools for measuring the institute. In India college assessments have been made compulsory by UGC. Naac has been offically recognised as the accrediation criteria. The Naac criteria has been based on seven criterias namely: 1. Curricular assessments, 2. Teaching learning and evaluation, 3. Research Consultancy and Extension, 4. Infrastructure and learning resources, 5. Student support and progression, 6. Governance leadership and management, 7. Innovation and best practices. The Naac tries to bench mark the institution for identification, sustainability, dissemination and adaption of best practices. It grades the institution according to this seven criteria and the funding of institution is based on these grades. Many of the colleges are struggling to get best of grades but they have not come across a systematic tool to achieve the results. Balanced Scorecard developed by Kaplan has been a successful tool for corporates to develop best of practices so as to increase their financial performance and also retain and increase their customers so as to grow the organization to next level.It is time to test this tool for an educational institute. Methodology: The paper tries to develop a prototype for college based on the secondary data. Once a prototype is developed the researcher based on questionnaire will try to test this tool for successful implementation. The success of this research will depend on its implementation of BSC on an institute and its grading improved due to this successful implementation. Limitation of time is a major constraint in this research as Naac cycle takes minimum 4 years for accreditation and reaccreditation the methodology will limit itself to secondary data and questionnaire to be circulated to colleges along with the prototype model of BSC. Conclusion: BSC is a successful tool for enhancing growth of an organization. Educational institutes are no exception to these. BSC will only have to be realigned to suit the Naac criteria. Once this prototype is developed the success will be tested only on its implementation but this research paper will be the first step towards developing this tool and will also initiate the success by developing a questionnaire and getting and evaluating the responses for moving to the next level of actual implementation

Keywords: balanced scorecard, bench marking, Naac, UGC

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Authors: Marius Nygaard, Ona Flindall

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The Palisaden student housing project was completed in August 2013 and was, with its eight floors, Norway’s tallest timber building at the time of completion. It was the first time cross-laminated-timber (CLT) was utilized at this scale in Norway. The project was the result of a concerted effort by a newly formed management company to establish CLT as a sustainable and financially competitive alternative to conventional steel and concrete systems. The introduction of CLT onto the student housing market proved so successful that by 2017 more than 4000 individual student residences will have been built using the same model of development and construction. The aim of this paper is to identify the key factors that enabled this breakthrough for CLT. It is based on an in-depth study of a series of housing projects and the role of the management company who both instigated and enabled this shift of CLT from the margin to the mainstream. Specifically, it will look at how a new building system was integrated into a marketing strategy that identified a market potential within the existing structure of the construction industry and within the economic restrictions inherent to student housing in Norway. It will show how a key player established a project model that changed both the patterns of cooperation and the information basis for decisions. Based on qualitative semi-structured interviews with managers, contractors and the interdisciplinary teams of consultants (architects, structural engineers, acoustical experts etc.) this paper will trace the introduction, expansion and evolution of CLT-based building systems in the student housing market. It will show how the project management firm’s position in the value chain enabled them to function both as a liaison between contractor and client, and between contractor and producer. A position that allowed them to improve the flow of information. This ensured that CLT was handled on equal terms to other structural solutions in the project specifications, enabling realistic pricing and risk evaluation. Secondly, this paper will describe and discuss how the project management firm established and interacted with a growing network of contractors, architects and engineers to pool expertise and broaden the knowledge base across Norway’s regional markets. Finally, it will examine the role of the client, the building typology, and the industrial and technological factors in achieving this breakthrough for CLT in the construction industry. This paper gives an in-depth view of the progression of a single case rather than a broad description of the state of the art of large-scale timber building in Norway. However, this type of study may offer insights that are important to the understanding not only of specific markets but also of how new technologies should be introduced in big and well-established industries.

Keywords: cross-laminated-timber (CLT), industry breakthrough, student housing, timber market

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Authors: Leigh G. Hayden, Susan E. Shepley, Cristina Passarelli, William Tingo

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Introduction: Sensory interventions are popular therapeutic and recreational approaches for people living with all stages of dementia. However, it is unknown which sensory interventions are used to achieve which outcomes across all subtypes of dementia. Methods: To address this gap, we conducted a scoping review of sensory interventions for people living with dementia. We conducted a search of the literature for any article published in English from 1 January 1990 to 1 June 2019, on any sensory or multisensory intervention targeted to people living with any kind of dementia, which reported on patient health outcomes. We did not include complex interventions where only a small aspect was related to sensory stimulation. We searched the databases Medline, CINHAL, and Psych Articles using our institutional discovery layer. We conducted all screening in duplicate to reduce Type 1 and Type 2 errors. The data from all included papers were extracted by one team member, and audited by another, to ensure consistency of extraction and completeness of data. Results: Our initial search captured 7654 articles, and the removal of duplicates (n=5329), those that didn’t pass title and abstract screening (n=1840) and those that didn’t pass full-text screening (n=281) resulted in 174 articles included. The countries with the highest publication in this area were the United States (n=59), the United Kingdom (n=26) and Australia (n=15). The most common type of interventions were music therapy (n=36), multisensory rooms (n=27) and multisensory therapies (n=25). Seven articles were published in the 1990’s, 55 in the 2000’s, and the remainder since 2010 (n=112). Discussion: Multisensory rooms have been present in the literature since the early 1990’s. However, more recently, nature/garden therapy, art therapy, and light therapy have emerged since 2008 in the literature, an indication of the increasingly diverse scholarship in the area. The least popular type of intervention is a traditional food intervention. Taste as a sensory intervention is generally avoided for safety reasons, however it shows potential for increasing quality of life. Agitation, behavior, and mood are common outcomes for all sensory interventions. However, light therapy commonly targets sleep. The majority (n=110) of studies have very small sample sizes (n=20 or less), an indicator of the lack of robust data in the field. Additional small-scale studies of the known sensory interventions will likely do little to advance the field. However, there is a need for multi-armed studies which directly compare sensory interventions, and more studies which investigate the use of layering sensory interventions (for example, adding an aromatherapy component to a lighting intervention). In addition, large scale studies which enroll people at early stages of dementia will help us better understand the potential of sensory and multisensory interventions to slow the progression of the disease.

Keywords: sensory interventions, dementia, scoping review

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Authors: Nidhi Malshe

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Background: Currently, there are approximately 1.3 billion individuals worldwide living with significant disabilities, which accounts for 16% of the global population—about 1 in 6 people. As the global population continues to grow, so does the number of people experiencing disabilities. Traffic accidents alone contribute to millions of injuries and disabilities each year, particularly among young people. Additionally, as life expectancy rises, more individuals are likely to experience disabilities in their later years. 27.0% of Canadians aged 15 and over, or 8 million people, had at least one disability in 2022. This represents an increase of 4.7 percentage points from 2017. A person with a disability earns 21.4% less on average as compared to a person without a disability. Using innovative and inclusive methods for accommodations, disability management, and employment, we can progress towards inclusive workplaces and potential income parity for this equity-seeking population. Objective: This study embraces innovative and inclusive approaches to disability management, thereby unlocking the advantages associated with a) fostering equal opportunities for all individuals, b) facilitating streamlined accommodations and making it easier for companies to accommodate people with disabilities, c) harnessing diverse perspectives to drive innovation and enhance overall productivity. Methodology: Literature review, assessments of specific needs and requirements in the workplace. a) Encourage the ability to think out of the box for potential workplace accommodations based on the specific needs of individuals. e.g., propose prolonged integration post disability. b) Perform a cost-benefit analysis of early interventions of return to work vs. duration on disability. c) Expand the scope of vocational assessment/retraining – e.g., retraining a person with permanent physical impairment to become a video game coder. d) Leverage the use of technology while planning to return to work e.g., speech-to-text software for persons with voice impairments. Hypothesized Results: Prolonged progression of return to work increases the potential for sustainable and productive employment. Co-developing a person-centric accommodation plan based on reported functional abilities and applying pioneering methods for extending accommodations to prevent secondary disabilities. Facilitate a sense of belonging by providing employees with benefits and initiatives that honor their unique contributions. Engage individuals with disabilities as active members of the planning committee to ensure the development of innovative and inclusive accommodations that address the needs of all. Conclusion: The global pandemic underscored the need for creativity in our daily routine. It is imperative to integrate the lessons learned from the pandemic, enhance them within employment, and return to work processes. These learnings can also be used to develop creative, distinct methods to ensure equal opportunities for everyone.

Keywords: disbaility management, diversity, inclusion, innovation

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Authors: Maha Atout, Pippa Hemingway, Jane Seymour

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A preliminary systematic review shows that health professionals experience a tension when communicating with the parents and family members of children with life-threatening and life-limiting conditions. On the one hand, they want to promote open and honest communication, while on the other, they are apprehensive about fostering an unrealistic sense of hope. Defining the boundaries between information that might offer reasonable hope versus that which results in false reassurance is challenging. Some healthcare providers worry that instilling a false sense of hope could motivate parents to seek continued aggressive treatment for their child, which in turn might cause the patient further unnecessary suffering. To date, there has been a lack of research in the Middle East regarding how healthcare providers do or should communicate bad news; in particular, the issue of hope in the field of paediatric palliative care has not been researched thoroughly. This study aims to explore, from the perspective of patients’ mothers, physicians, and nurses, the experience of communicating and receiving bad news in the care of children with palliative care needs. Data were collected using a collective qualitative case study approach across three paediatric units in a Jordanian hospital. Two data collection methods were employed: participant observation and semi-structured interviews. The overall number of cases was 15, with a total of 56 interviews with mothers (n=24), physicians (n=12), and nurses (n=20) completed, as well as 197 observational hours logged. The findings demonstrate that mothers wanted their doctors to provide them with hopeful information about the future progression of their child’s illness. Although some mothers asked their doctors to provide them with honest information regarding the condition of their child, they still considered a sense of hope to be essential for coping with caring for their child. According to mothers, hope was critical to treatment as it helped them to stay committed to the treatment and protected them to some extent from the extreme emotional suffering that would occur if they lost hope. The health professionals agreed with the mothers on the importance of hope, so long as it was congruent with the stage and severity of each patient’s disease. The findings of this study conclude that while parents typically insist on knowing all relevant information when their child is diagnosed with a severe illness, they considered hope to be an essential part of life, and they found it very difficult to handle suffering without any glimmer of it. This study finds that using negative terms has extremely adverse effects on the parents’ emotions. Hence, although the mothers asked the doctors to be as honest as they could, they still wanted the physicians to provide them with a positive message by communicating this information in a sensitive manner including hope.

Keywords: health professionals, children, communication, hope, information, mothers, palliative care

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Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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Authors: Yelena Agranovich, Larissa Ageyeva, Aigul Syzdykbayeva, Violetta Tyan

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The modernization of the education system in the Republic of Kazakhstan is aimed at improving the quality of teacher training and enhancing key competencies among teachers. The current professional standard ‘Teacher’ defines the general characteristics of teachers’ activities, key competencies, and criteria according to relevant qualification categories structured on the principle of progression, thereby enabling Continuous Professional Development (CPD). The essence of CPD lies in the constant integration of new knowledge and skills that help teachers adapt to changes in the education system, in technologies, and teaching methods. This developmental process enables teachers to stay updated on recent scientific achievements, innovations, and modern pedagogical practices. Continuous learning helps teachers remain flexible and open to new developments, creating conditions for improving educational quality and fostering students' personal growth. This study aims to address the following objectives: analysis of international CPD practices, identification of conceptual foundations, and investigation of CPD implementation mechanisms in Kazakhstan. The core principles of CPD are identified as longitudinality, systematicity, and fragmentation. CPD implementation is based on various theoretical approaches: axiological, systemic, competency-based, activity-based, and learner-centered. The study analyzes leading models of teacher CPD, with a target sample that includes countries such as Australia, Japan, South Korea, England, Singapore, Sweden, Finland, and Kazakhstan. The research methods include analysis (comparative, historical, content analysis, systematic), case studies of CPD models, and synthesis and systematization of scientific data. As research results, the mechanisms for CPD implementation in Kazakhstan will be identified, along with further perspectives on transforming resources within the teacher professional development system. In comparing CPD models from various countries, it is noted that teacher CPD in the Republic of Kazakhstan: (1) is implemented through educational programs, professional development courses, teacher certification, professional networks, in-school professional development, self-education, and self-assessment; (2) includes the development of pedagogical values and competencies (tolerance, inclusivity, communication, critical thinking, creativity, reflection, etc.); (3) is carried out based on traditional forms (professional development courses, retraining) and informal forms (self-learning, self-development, experience sharing and exchange). Further research will focus on creating a digital ecosystem for teacher CPD, based on an educational platform that facilitates individualized professional development pathways for teachers (competency diagnostics, course selection, and a methodological system of course and post-course support for teachers).

Keywords: continuous professional development, CPD models, professional development, professional upgrading, teacher, teacher training

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Authors: Shamim Mushtaq, Moazzam Shahid

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Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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Authors: Majed A. Alsalem

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In our contemporary world, literacy is an essential skill that enables students to increase their efficiency in managing the many assignments they receive that require understanding and knowledge of the world around them. In addition, literacy enhances student participation in society improving their ability to learn about the world and interact with others and facilitating the exchange of ideas and sharing of knowledge. Therefore, literacy needs to be studied and understood in its full range of contexts. It should be seen as social and cultural practices with historical, political, and economic implications. This study aims to rebuild and reorganize the instructional designs that have been used for deaf and hard-of-hearing (DHH) students to improve their literacy level. The most critical part of this process is the teachers; therefore, teachers will be the center focus of this study. Teachers’ main job is to increase students’ performance by fostering strategies through collaborative teamwork, higher-order thinking, and effective use of new information technologies. Teachers, as primary leaders in the learning process, should be aware of new strategies, approaches, methods, and frameworks of teaching in order to apply them to their instruction. Literacy from a wider view means acquisition of adequate and relevant reading skills that enable progression in one’s career and lifestyle while keeping up with current and emerging innovations and trends. Moreover, the nature of literacy is changing rapidly. The notion of new literacy changed the traditional meaning of literacy, which is the ability to read and write. New literacy refers to the ability to effectively and critically navigate, evaluate, and create information using a range of digital technologies. The term new literacy has received a lot of attention in the education field over the last few years. New literacy provides multiple ways of engagement, especially to those with disabilities and other diverse learning needs. For example, using a number of online tools in the classroom provides students with disabilities new ways to engage with the content, take in information, and express their understanding of this content. This study will provide teachers with the highest quality of training sessions to meet the needs of DHH students so as to increase their literacy levels. This study will build a platform between regular instructional designs and digital materials that students can interact with. The intervention that will be applied in this study will be to train teachers of DHH to base their instructional designs on the notion of Technology Acceptance Model (TAM) theory. Based on the power analysis that has been done for this study, 98 teachers are needed to be included in this study. This study will choose teachers randomly to increase internal and external validity and to provide a representative sample from the population that this study aims to measure and provide the base for future and further studies. This study is still in process and the initial results are promising by showing how students have engaged with digital books.

Keywords: deaf and hard of hearing, digital books, literacy, technology

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Authors: C. Watson, T. Glare, M. O'Callaghan, M. Hurst

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The endemic New Zealand grass grub (Costelytra giveni, Coleoptera: Scarabaeidae) is an economically significant grassland pest in New Zealand. Due to their impacts on production within the agricultural sector, one of New Zealand's primary industries, several methods are being used to either control or prevent the establishment of new grass grub populations in the pasture. One such method involves the use of a biopesticide based on the bacterium Serratia entomophila. This species is one of the causative agents of amber disease, a chronic disease of the larvae which results in death via septicaemia after approximately 2 to 3 months. The ability of S. entomophila to cause amber disease is dependant upon the presence of the amber disease associated plasmid (pADAP), which encodes for the key virulence determinants required for the establishment and maintenance of the disease. Following the collapse of grass grub populations within the soil, resulting from either natural population build-up or application of the bacteria, non-pathogenic plasmid-free Serratia strains begin to predominate within the soil. Whilst the interactions between S. entomophila and grass grub larvae are well studied, less information is known on the interactions between plasmid-bearing and plasmid-free strains, particularly the potential impact of these interactions upon the efficacy of an applied biopesticide. Using a range of constructed strains with antibiotic tags, in vitro (broth culture) and in vivo (soil and larvae) experiments were conducted using inoculants comprised of differing ratios of isogenic pathogenic and non-pathogenic Serratia strains, enabling the relative growth of pADAP+ and pADAP- strains under competition conditions to be assessed. In nutrient-rich, the non-pathogenic pADAP- strain outgrew the pathogenic pADAP+ strain by day 3 when inoculated in equal quantities, and by day 5 when applied as the minority inoculant, however, there was an overall gradual decline in the number of viable bacteria for both strains over a 7-day period. Similar results were obtained in additional experiments using the same strains and continuous broth cultures re-inoculated at 24-hour intervals, although in these cultures, the viable cell count did not diminish over the 7-day period. When the same ratios were assessed in soil microcosms with limited available nutrients, the strains remained relatively stable over a 2-month period. Additionally, in vivo grass grub co-infections assays using the same ratios of tagged Serratia strains revealed similar results to those observed in the soil, but there was also evidence of horizontal transfer of pADAP from the pathogenic to the non-pathogenic strain within the larval gut after a period of 4 days. Whilst the influence of competition is more apparent in broth cultures than within the soil or larvae, further testing is required to determine whether this competition between pathogenic and non-pathogenic Serratia strains has any influence on efficacy and disease progression, and how this may impact on the ability of S. entomophila to cause amber disease within grass grub larvae when applied as a biopesticide.

Keywords: biological control, entomopathogen, microbial ecology, New Zealand

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

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

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Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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Authors: Tuba Denkceken, Ayse Nur Sarı, Volkan Ihsan Tore, Mahmut Denkceken

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The aim of the presented study was to develop a newly motorized spectroscopy system. Our system is composed of probe and motor parts. The probe part consists of bioimpedance and fiber optic components that include two platinum wires (each 25 micrometer in diameter) and two fiber cables (each 50 micrometers in diameter) respectively. Probe was examined on tissue phantom (polystyrene microspheres with different diameters). In the bioimpedance part of the probe current was transferred to the phantom and conductivity information was obtained. Adjacent two fiber cables were used in the fiber optic part of the system. Light was transferred to the phantom by fiber that was connected to the light source and backscattered light was collected with the other adjacent fiber for analysis. It is known that the nucleus expands and the nucleus-cytoplasm ratio increases during the cancer progression in the cell and this situation is one of the most important criteria for evaluating the tissue for pathologists. The sensitivity of the probe to particle (nucleus) size in phantom was tested during the study. Spectroscopic data obtained from our system on phantom was evaluated by multivariate statistical analysis. Thus the information about the particle size in the phantom was obtained. Bioimpedance and fiber optic experiments results which were obtained from polystyrene microspheres showed that the impedance value and the oscillation amplitude were increasing while the size of particle was enlarging. These results were compatible with the previous studies. In order to motorize the system within the motor part, three driver electronic circuits were designed primarily. In this part, supply capacitors were placed symmetrically near to the supply inputs which were used for balancing the oscillation. Female capacitors were connected to the control pin. Optic and mechanic switches were made. Drivers were structurally designed as they could command highly calibrated motors. It was considered important to keep the drivers’ dimension as small as we could (4.4x4.4x1.4 cm). Then three miniature step motors were connected to each other along with three drivers. Since spectroscopic techniques are quantitative methods, they yield more objective results than traditional ones. In the future part of this study, it is planning to get spectroscopic data that have optic and impedance information from the cell culture which is normal, low metastatic and high metastatic breast cancer. In case of getting high sensitivity in differentiated cells, it might be possible to scan large surface tissue areas in a short time with small steps. By means of motorize feature of the system, any region of the tissue will not be missed, in this manner we are going to be able to diagnose cancerous parts of the tissue meticulously. This work is supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) through 3001 project (115E662).

Keywords: motorized spectroscopy, phantom, scanning system, tissue scanning

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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Authors: Sara R. Knigge, Sugat R. Tuladhar, Alexander Becker, Tobias Schilling, Birgit Glasmacher

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Commercially available mechanical or biological heart valve prostheses both tend to fail long-term due to thrombosis, calcific degeneration, infection, or immunogenic rejection. Moreover, these prostheses are non-viable and do not grow with the patients, which is a problem for young patients. As a result, patients often need to undergo redo-operations. Tissue-engineered (TE) heart valves based on degradable electrospun fiber scaffolds represent a promising approach to overcome these limitations. Such scaffolds need sufficient mechanical properties to withstand the hydrodynamic stress of intracardiac hemodynamics. Additionally, the scaffolds should be colonized by autologous or homologous cells to facilitate the in vivo remodeling of the scaffolds to a viable structure. This study investigates how process parameters of electrospinning and degradation affect the mechanical properties of electrospun scaffolds made of FDA-approved, biodegradable polymer polycaprolactone (PCL). Fiber mats were produced from a PCL/tetrafluoroethylene solution by electrospinning. The e-spinning process was varied in terms of scaffold thickness, fiber diameter, fiber orientation, and fiber interconnectivity. The morphology of the fiber mats was characterized with a scanning electron microscope (SEM). The mats were degraded in different solutions (cell culture media, SBF, PBS and 10 M NaOH-Solution). At different time points of degradation (2, 4 and 6 weeks), tensile and cyclic loading tests were performed. Fresh porcine pericardium and heart valves served as a control for the mechanical assessment. The progression of polymer degradation was quantified by SEM and differential scanning calorimetry (DSC). Primary Human aortic endothelial cells (HAECs) and Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were seeded on the fiber mats to investigate the cell colonization potential. The results showed that both the electrospinning parameters and the degradation significantly influenced the mechanical properties. Especially the fiber orientation has a considerable impact and leads to a pronounced anisotropic behavior of the scaffold. Preliminary results showed that the polymer became strongly more brittle over time. However, the embrittlement can initially only be detected in the mechanical test. In the SEM and DSC investigations, neither morphological nor thermodynamic changes are significantly detectable. Live/Dead staining and SEM imaging of the cell-seeded scaffolds showed that HAECs and iPSC-ECs were able to grow on the surface of the polymer. In summary, this study's results indicate a promising approach to the development of a TE aortic heart valve based on an electrospun scaffold.

Keywords: electrospun scaffolds, long-term polymer degradation, mechanical behavior of electrospun PCL, tissue engineered aortic heart valve

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Authors: Aaron Derner

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Unlike the histories of France, the UK, or even Spain, the Russian colonial past often dissolves before the seemingly more salient Cold War figurations or Soviet dissolution. The obvious explanation behind Caucasian states’ roles—that of Russian-propped governments obeying the whims of their patron—is but the latest instance of such oversight. Where the results of colonial social and cultural interactions are indelibly stamped across France, Algeria, and every other former (and current) French holding, so to are the Muscovite and Russian colonial ambitions embedded within the modern politics and cultures of both Russia and the Caucasus. Russian colonial artefacts are enhanced and perhaps granted an additional social explanatory edge over those of the ‘typical’ colonizers, by the cyclical adoration for and noisy rejection of European cultural markers over the centuries, along with the somewhat unusual composition of the Cossacks: Russia’s main agents of colonialization within the Caucasian frontier. The story of Russia and Chechnya, of all the Caucasus, is of the manufacture of social and individual identity through “modes of subjectification” inherent within the region’s colonial history and driven by the triangular interactions between three main groups: the Cossacks, the Caucasian Mountain Tribes, and the Russian Metropol. Together, interactions between these social groups worked to shape and transform the lifestyles and institutional pathologies that constitute the Russian and Chechen states and the politics between them. At the core of this (Western) state-building is the simultaneous and seemingly contradictory desire to be more Western and emulate Western cultural and political practices while also desperately grasping for a uniquely Russian identity. This sits somewhat ironically against the backdrop that Russia hosted a frontier-based settler society and had established that distinctly European feature of settler colonialism early in its history—arguably establishing a claim to being the most “colonial” of the colonial powers. There is no doubt that these forces worked to shape contemporary Russian political and social identity—apparent in the mythic popularity of the Cossack in Russian literature, politics, and academic discourse. What needs to be expanded from the current narrative, however, is that beyond the Cossack identity’s attractiveness on the grounds of its tones of freedom and resistance to unjust authority, the identity is rooted in the imperial ambitions and colonial experiences of the Russian state, and is, therefore, a direct marker of domination and subjectification. Adding an unusual dimension to this not-uncommon cultural progression, the Russian state needed to colonize both the Caucases and the Russian Cossacks, appropriating them in much the same way they appropriated the Circassian mountain tribes. The focus of this paper is not to tell yet another story of how one culture entered an area to overpower another but how a ‘powerful,’ ‘modern,’ ‘Western(ish)’ culture was profoundly and continually changed through its contact with a group of tribal ‘savages’ and ‘braves.’

Keywords: Russia, chechnya, subjectification, caucasus, cossacks, Ukraine

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Authors: Lei Li, Ping Yin, Haneen Khreis

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Stroke is the second leading cause of death and a third leading cause of death and disability worldwide in 2019. Given the significant role of environmental factors in stroke development and progression, it is essential to investigate the effect of air pollution on stroke occurrence while considering the modifying effects of meteorological variables. This study aimed to evaluate the association between short-term exposure to air pollution and the incidence of stroke subtypes in Shenzhen, China, and to explore the potential interactions of meteorological factors with air pollutants. The study analyzed data from January 1, 2006, to December 31, 2014, including 88,214 cases of ischemic stroke and 30,433 cases of hemorrhagic stroke among residents of Shenzhen. Using a time-stratified case–crossover design with conditional quasi-Poisson regression, the study estimated the percentage changes in stroke morbidity associated with short-term exposure to nitrogen dioxide (NO₂), sulfur dioxide (SO₂), particulate matter less than 10 mm in aerodynamic diameter (PM10), carbon monoxide (CO), and ozone (O₃). A five-day moving average of air pollution was applied to capture the cumulative effects of air pollution. The estimates were further stratified by sex, age, education level, and season. The additive and multiplicative interaction between air pollutants and meteorologic variables were assessed by the relative excess risk due to interaction (RERI) and adding the interactive term into the main model, respectively. The study found that NO₂ was positively associated with ischemic stroke occurrence throughout the year and in the cold season (November through April), with a stronger effect observed among men. Each 10 μg/m³ increment in the five-day moving average of NO₂ was associated with a 2.38% (95% confidence interval was 1.36% to 3.41%) increase in the risk of ischemic stroke over the whole year and a 3.36% (2.04% to 4.69%) increase in the cold season. The harmful effect of CO on ischemic stroke was observed only in the cold season, with each 1 mg/m³ increment in the five-day moving average of CO increasing the risk by 12.34% (3.85% to 21.51%). There was no statistically significant additive interaction between individual air pollutants and temperature or relative humidity, as demonstrated by the RERI. The interaction term in the model showed a multiplicative antagonistic effect between NO₂ and temperature (p-value=0.0268). For hemorrhagic stroke, no evidence of the effects of any individual air pollutants was found in the whole population. However, the RERI indicated a statistically additive and multiplicative interaction of temperature on the effects of PM10 and O₃ on hemorrhagic stroke onset. Therefore, the insignificant conclusion should be interpreted with caution. The study suggests that environmental NO₂ and CO might increase the morbidity of ischemic stroke, particularly during the cold season. These findings could help inform policy decisions aimed at reducing air pollution levels to prevent stroke and other health conditions. Additionally, the study provides valuable insights into the interaction between air pollution and meteorological variables, which underscores the need for further research into the complex relationship between environmental factors and health.

Keywords: air pollution, meteorological variables, interactive effect, seasonal pattern, stroke

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Thimira Pasas P, Nirmala Priyadarshani M, Ishani R

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Obesity is a global health issue. Early identification is essential to plan interventions and intervene than to reduce the worsening of obesity and its consequences on the health issues of the individual. Childhood obesity is multifactorial, with both modifiable and unmodifiable risk factors. A genetically susceptible individual (unmodifiable), when placed in an obesogenic environment (modifiable), is likely to become obese in onset and progression. The present study was conducted to identify the age of onset of childhood obesity and the influence of modifiable risk factors for childhood obesity among school children living in a suburban area of Sri Lanka. The study population was aged 11-12 years of Piliyandala Educational Zone. Data were collected from 11–12-year-old school children attending government schools in the Piliyandala Educational Zone. They were using a validated, pre-tested self-administered questionnaire. A stratified random sampling method was performed to select schools and to select a representative sample to include all 3 types of government schools of students due to the prevailing pandemic situation, information from the last school medical inspection on data from 2020used for this purpose. For each obese child identified, 2 non-obese children were selected as controls. A single representative from the area was selected by using a systematic random sampling method with a sampling interval of 3. Data was collected using a validated, pre-tested self-administered questionnaire and the Child Health Development Record of the child. An introduction, which included explanations and instructions for filing the questionnaire, was carried out as a group activity prior to distributing the questionnaire among the sample. The results of the present study aligned with the hypothesis that the age of onset of childhood obesity and prediction must be within the first two years of child life. A total of 130 children (66 males: 64 females) participated in the study. The age of onset of obesity was seen to be within the first two years of life. The risk of obesity at 11-12 years of age was Obesity risk was identified at 3-time s higher among females who underwent rapid weight gain within their infancy period. Consuming milk prior to breakfast emerged as a risk factor that increases the risk of obesity by three times. The current study found that the drink before breakfast tends to increase the obesity risk by 3-folds, especially among obese females. Proper monitoring must be carried out to identify the rapid weight gain, especially within the first 2 years of life. Consumption of mug milk before breakfast tends to increase the obesity risk by 3 times. Identification of the confounding factors, proper awareness of the mothers/guardians and effective proper interventions need to be carried out to reduce the obesity risk among school children in the future.

Keywords: childhood obesity, school children, age of onset, weight gain, feeding pattern, activity level

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Authors: Paola Millare, Nelinda Catherine Pangilinan

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Background and Aim: Cervical cancer is the most commonly diagnosed gynecological malignancy during pregnancy. Owing to the rarity of the disease, and the complexity of all factors that have to be taken into consideration, standardization of treatment is very difficult. Cervical cancer is the second most common malignancy among women. The treatment of cancer during pregnancy is most challenging in the case of cervical cancer, since the pregnant uterus itself is affected. This report aims to present a case of cervical cancer in a pregnant woman and how to manage this case and several issues accompanied with it. Methods: This is a case of a 28 year-old, Gravida 4 Para 2 (1111), who presented with watery to mucoid, whitish, non-foul smelling and increasing in amount. Internal examination revealed normal external genitalia, parous outlet, cervix was transformed into a fungating mass measuring 5x4 cm, with left parametrial involvement, body of uterus was enlarged to 24 weeks size, no adnexal mass or tenderness. She had cervical punch biopsy, which revealed, adenocarcinoma, well-differentiated cervical tissue. Standard management for cases with stage 2B cervical carcinoma was to start radiation or radical hysterectomy. In the case of patients diagnosed with cervical cancer and currently pregnant, these kind of management will result to fetal loss. The patient still declined the said management and opted to delay the treatment and wait for her baby to reach at least term and proceed to cesarean section as route of delivery. Results: The patient underwent an elective cesarean section at 37th weeks age of gestation, with an outcome of a term, live baby boy APGAR score 7,9 birthweight 2600 grams. One month postpartum, the patient followed up and completed radiotherapy, chemotherapy and brachytherapy. She was advised to go back after 6 months for monitoring. On her last check up, an internal examination was done which revealed normal external genitalia, vagina admits 2 fingers with ease, there is a palpable fungating mass at the cervix measuring 2x2 cm. A repeat gynecologic oncologic ultrasound was done revealing cervical mass, endophytic, grade 1 color score with stromal invasion 35% post radiation reactive lymph nodes with intact paracolpium, pericervical, and parametrial involvement. The patient was then advised to undergo pelvic boost and for close monitoring of the cervical mass. Conclusion: Cervical cancer in pregnancy is rare but is a dilemma for women and their physicians. Treatment should be multidisciplinary and individualized following careful counseling. In this case, the treatment was clearly on the side of preventing the progression of cervical cancer while she is pregnant, however due to ethical reasons, the management deviates on the right of the patient to decide for her own health and her unborn child. The collaborative collection of data relating to treatment and outcome is strongly encouraged.

Keywords: cancer, cervical, ethical, pregnancy

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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Authors: Efstratios Karavasilis, Foteini Christidi, Georgios Velonakis, Agapi Plousi, Kalliopi Platoni, Nikolaos Kelekis, Ioannis Evdokimidis, Efstathios Efstathopoulos

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Introduction: Advanced structural and functional neuroimaging techniques contribute to the study of anatomical and functional brain connectivity and its role in the pathophysiology and symptoms’ heterogeneity in several neurodegenerative disorders, including multiple sclerosis (MS). Aim: In the present study, we applied multiparametric neuroimaging techniques to investigate the structural and functional cortico-cerebellar changes in MS patients. Material: We included 51 MS patients (28 with clinically isolated syndrome [CIS], 31 with relapsing-remitting MS [RRMS]) and 51 age- and gender-matched healthy controls (HC) who underwent MRI in a 3.0T MRI scanner. Methodology: The acquisition protocol included high-resolution 3D T1 weighted, diffusion-weighted imaging and echo planar imaging sequences for the analysis of volumetric, tractography and functional resting state data, respectively. We performed between-group comparisons (CIS, RRMS, HC) using CAT12 and CONN16 MATLAB toolboxes for the analysis of volumetric (cerebellar gray matter density) and functional (cortico-cerebellar resting-state functional connectivity) data, respectively. Brainance suite was used for the analysis of tractography data (cortico-cerebellar white matter integrity; fractional anisotropy [FA]; axial and radial diffusivity [AD; RD]) to reconstruct the cerebellum tracts. Results: Patients with CIS did not show significant gray matter (GM) density differences compared with HC. However, they showed decreased FA and increased diffusivity measures in cortico-cerebellar tracts, and increased cortico-cerebellar functional connectivity. Patients with RRMS showed decreased GM density in cerebellar regions, decreased FA and increased diffusivity measures in cortico-cerebellar WM tracts, as well as a pattern of increased and mostly decreased functional cortico-cerebellar connectivity compared to HC. The comparison between CIS and RRMS patients revealed significant GM density difference, reduced FA and increased diffusivity measures in WM cortico-cerebellar tracts and increased/decreased functional connectivity. The identification of decreased WM integrity and increased functional cortico-cerebellar connectivity without GM changes in CIS and the pattern of decreased GM density decreased WM integrity and mostly decreased functional connectivity in RRMS patients emphasizes the role of compensatory mechanisms in early disease stages and the disintegration of structural and functional networks with disease progression. Conclusions: In conclusion, our study highlights the added value of multimodal neuroimaging techniques for the in vivo investigation of cortico-cerebellar brain changes in neurodegenerative disorders. An extension and future opportunity to leverage multimodal neuroimaging data inevitably remain the integration of such data in the recently-applied mathematical approaches of machine learning algorithms to more accurately classify and predict patients’ disease course.

Keywords: advanced neuroimaging techniques, cerebellum, MRI, multiple sclerosis

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Authors: Neeraj Vij, Amber Brennan, Jenni Winters, Hadi Salehi, Hamy Temkit, Emily Andrisevic, Mohan V. Belthur

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Idiopathic clubfoot is a common lower extremity deformity with an incidence of 1:500. The Ponseti Method is well known as the gold standard of treatment. However, there is limited functional data demonstrating correction of the clubfoot after treatment with the Ponseti method. The purpose of this study was to study the clinical and functional outcomes after the Ponseti method with the Clubfoot Disease-Specific Instrument (CDS) and pedobarography. This IRB-approved prospective study included patients aged 3-18 who were treated for idiopathic clubfoot with the Ponseti method between January 2008 and December 2018. Age-matched controls were identified through siblings of clubfoot patients and other community members. Treatment details were collected through a chart review of the included patients. Laboratory assessment included a physical exam, gait analysis, and pedobarography. The Pediatric Outcomes Data Collection Instrument and the Clubfoot Disease-Specific Instrument were also obtained on clubfoot patients (CF). The Wilcoxson rank-sum test was used to study differences between the CF patients and the typically developing (TD) patients. Statistical significance was set at p < 0.05. There were a total of 37 enrolled patients in our study. 21 were priorly treated for CF and 16 were TD. 94% of the CF patients had bilateral involvement. The age at the start of treatment was 29 days, the average total number of casts was seven to eight, and the average total number of casts after Achilles tenotomy was one. The reoccurrence rate was 25%, tenotomy was required in 94% of patients, and ≥1 tenotomy was required in 25% of patients. There were no significant differences between step length, step width, stride length, force-time integral, maximum peak pressure, foot progression angles, stance phase time, single-limb support time, double limb support time, and gait cycle time between children treated with the Ponseti method and typically developing children. The average post-treatment Pirani and Dimeglio scores were 5.50±0.58 and 15.29±1.58, respectively. The average post-treatment PODCI subscores were: Upper Extremity: 90.28, Transfers: 94.6, Sports: 86.81, Pain: 86.20, Happiness: 89.52, Global: 88.6. The average post-treatment Clubfoot Disease-Specific Instrument scores subscores were: Satisfaction: 73.93, Function: 80.32, Overall: 78.41. The Ponseti Method has a very high success rate and remains to be the gold standard in the treatment of idiopathic clubfoot. Timely management leads to good outcomes and a low need for repeated Achilles tenotomy. Children treated with the Ponseti method demonstrate good functional outcomes as measured through pedobarography. Pedobarography may have clinical utility in studying congenital foot deformities. Objective measures for hours of brace wear could represent an improvement in clubfoot care.

Keywords: functional outcomes, pediatric deformity, patient-reported outcomes, talipes equinovarus

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Authors: Ting-I Lin

Abstract:

Objective: This article explores the nursing care experience of a 51-year-old terminal lung cancer patient admitted to the intensive care unit (ICU) following an upper right lobectomy. The patient initially sought emergency treatment due to worsening cough and dyspnea, which led to the placement of an endotracheal tube following sudden deterioration. Subsequent CT scans and chest X-rays revealed a tumor in the upper right lung with metastases to the lungs, liver, bones, and adrenal glands. The patient underwent a right upper lobectomy and a wedge resection of the right middle lobe. Pathology staging: T4N3M1c and the patient was diagnosed with advanced cancer postoperatively. Method: During the care period, nursing staff continuously monitored the patient’s physiological data through observations, direct care, interviews, physical assessments, and review of the patient’s medical records. The nursing team collaborated with the critical care team and the palliative care team, using Gordon's Eleven Functional Health Patterns to conduct a comprehensive assessment. The key health problems identified included pain related to postoperative cancer resection and invasive devices, fear of death due to rapid disease progression, and altered tissue perfusion associated with hemodynamic instability. Results: Postoperatively, the patient experienced pain from the surgical wound and dyspnea due to extensive metastasis, often leading to confusion. Through the adjustment of pain medication, the patient’s discomfort was alleviated, using Morphine 8 mg in 0.9% normal saline 60 ml IV drip q6h prn, and Ultracet 37.5 mg/325 mg 1# PO q6h. Additionally, lavender essential oil inhalation and limb massage were provided for 15 minutes four times a day. The patient’s FLACC pain score decreased from 7 to below 3. After respiratory training, the endotracheal tube was successfully removed, and the patient was weaned off the ventilator. Triflow exercises were used to promote alveolar expansion, with the goal of achieving 2 balls for 10 seconds, 5 repetitions per session, 6-8 times a day. The patient’s breathing stabilized at 16-18 breaths per minute, body temperature remained between 35.8°C and 36.1°C, and the mean arterial pressure was maintained between 60-80 mmHg. Conclusion: The critical care team and the palliative care team held a family meeting to discuss not only the patient’s care but also the emotional well-being of the family. Visiting hours were increased to two times per day, one hour each time, allowing the patient and family to express love and gratitude, which strengthened their emotional connection and reduced the patient’s anxiety from severe to mild. The family expressed that they had no regrets. After the patient was transferred to the general ward, the nursing team continued to provide end-of-life care with genuine empathy, compassion, and religious support, helping both the patient and family through the final stage of life.

Keywords: multiple metastases, lung cancer, palliative care, nursing experience

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Authors: Damian Islas

Abstract:

Debates on realism in science concern two different questions: (I) whether the unobservable entities posited by theories can be known; and (II) whether any knowledge we have of them is objective or not. Question (I) arises from the doubt that since observation is the basis of all our factual knowledge, unobservable entities cannot be known. Question (II) arises from the doubt that since scientific representations are inextricably laden with the subjective, idiosyncratic, and a priori features of human cognition and scientific practice, they cannot convey any reliable information on how their objects are in themselves. A way of understanding scientific realism (SR) is through three lines of inquiry: ontological, semantic, and epistemological. Ontologically, scientific realism asserts the existence of a world independent of human mind. Semantically, scientific realism assumes that theoretical claims about reality show truth values and, thus, should be construed literally. Epistemologically, scientific realism believes that theoretical claims offer us knowledge of the world. Nowadays, the literature on scientific realism has proceeded rather far beyond the realism versus antirealism debate. This stance represents a middle-ground position between the two according to which science can attain justified true beliefs concerning relational facts about the unobservable realm but cannot attain justified true beliefs concerning the intrinsic nature of any objects occupying that realm. That is, the structural content of scientific theories about the unobservable can be known, but facts about the intrinsic nature of the entities that figure as place-holders in those structures cannot be known. There are two possible versions of SR: Epistemological Structural Realism (ESR) and Ontic Structural Realism (OSR). On ESR, an agnostic stance is preserved with respect to the natures of unobservable entities, but the possibility of knowing the relations obtaining between those entities is affirmed. OSR includes the rather striking claim that when it comes to the unobservables theorized about within fundamental physics, relations exist, but objects do not. Focusing on ESR, questions arise concerning its ability to explain the empirical success of a theory. Empirical success certainly involves predictive success, and predictive success implies a theory’s power to make accurate predictions. But a theory’s power to make any predictions at all seems to derive precisely from its core axioms or laws concerning unobservable entities and mechanisms, and not simply the sort of structural relations often expressed in equations. The specific challenge to ESR concerns its ability to explain the explanatory and predictive power of successful theories without appealing to their substantive ontologies, which are often not preserved by their successors. The response to this challenge will depend on the various and subtle different versions of ESR and OSR stances, which show a sort of progression through eliminativist OSR to moderate OSR of gradual increase in the ontological status accorded to objects. Knowing the relations between unobserved entities is methodologically identical to assert that these relations between unobserved entities exist.

Keywords: eliminativist ontic structural realism, epistemological structuralism, moderate ontic structural realism, ontic structuralism

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Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

Abstract:

Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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