Search results for: cognitive therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3605

Search results for: cognitive therapy

305 Relationship between Glycated Hemoglobin in Adolescents with Type 1 Diabetes Mellitus and Parental Anxiety and Depression

Authors: Evija Silina, Maris Taube, Maksims Zolovs

Abstract:

Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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304 Study on the Focus of Attention of Special Education Students in Primary School

Authors: Tung-Kuang Wu, Hsing-Pei Hsieh, Ying-Ru Meng

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Special Education in Taiwan has been facing difficulties including shortage of teachers and lack in resources. Some students need to receive special education are thus not identified or admitted. Fortunately, information technologies can be applied to relieve some of the difficulties. For example, on-line multimedia courseware can be used to assist the learning of special education students and take pretty much workload from special education teachers. However, there may exist cognitive variations between students in special or regular educations, which suggests the design of online courseware requires different considerations. This study aims to investigate the difference in focus of attention (FOA) between special and regular education students of primary school in viewing the computer screen. The study is essential as it helps courseware developers in determining where to put learning elements that matter the most on the right position of screen. It may also assist special education specialists to better understand the subtle differences among various subtypes of learning disabilities. This study involves 76 special education students (among them, 39 are students with mental retardation, MR, and 37 are students with learning disabilities, LDs) and 42 regular education students. The participants were asked to view a computer screen showing a picture partitioned into 3 × 3 areas with each area filled with text or icon. The subjects were then instructed to mark on the prior given paper sheets, which are also partitioned into 3 × 3 grids, the areas corresponding to the pictures on the computer screen that they first set their eyes on. The data are then collected and analyzed. Major findings are listed: 1. In both text and icon scenario, significant differences exist in the first preferred FOA between special and regular education students. The first FOA for the former is mainly on area 1 (upper left area, 53.8% / 51.3% for MR / LDs students in text scenario; and 53.8% / 56.8% for MR / LDs students in icons scenario), while the latter on area 5 (middle area, 50.0% and 57.1% in text and icons scenarios). 2. The second most preferred area in text scenario for students with MR and LDs are area 2 (upper-middle, 20.5%) and 5 (middle area, 24.3%). In icons scenario, the results are similar, but lesser in percentage. 3. Students with LDs that show similar preference (either in text or icons scenarios) in FOA to regular education students tend to be of some specific sub-type of learning disabilities. For instance, students with LDs that chose area 5 (middle area, either in text or icon scenario) as their FOA are mostly ones that have reading or writing disability. Also, three (out of 13) subjects in this category, after going through the rediagnosis process, were excluded from being learning disabilities. In summary, the findings suggest when designing multimedia courseware for students with MR and LDs, the essential learning elements should be placed on area 1, 2 and 5. In addition, FOV preference may also potentially be used as an indicator for diagnosing students with LDs.

Keywords: focus of attention, learning disabilities, mental retardation, on-line multimedia courseware, special education

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303 Early Return to Play in Football Player after ACL Injury: A Case Report

Authors: Nicola Milani, Carla Bellissimo, Davide Pogliana, Davide Panzin, Luca Garlaschelli, Giulia Facchinetti, Claudia Casson, Luca Marazzina, Andrea Sartori, Simone Rivaroli, Jeff Konin

Abstract:

The patient is a 26 year-old male amateur football player from Milan, Italy; (81kg; 185cm; BMI 23.6 kg/m²). He sustained a non-contact anterior cruciate ligament tear to his right knee in June 2021. In September 2021, his right knee ligament was reconstructed using a semitendinosus graft. The injury occurred during a football match on natural grass with typical shoes on a warm day (32 degrees celsius). Playing as a defender he sustained the injury during a change of direction, where the foot was fixated on the grass. He felt pain and was unable to continue playing the match. The surgeon approved his rehabilitation to begin two weeks post-operative. The initial physiotherapist assessment determined performing two training sessions per day within the first three months. In the first three weeks, the pain was 4/10 on Numerical Rating Scale (NRS), no swelling, a range of motion was 0-110°, with difficulty fully extending his knee and minimal quadriceps activation. Crutches were discontinued at four weeks with improved walking. Active exercise, electrostimulator, physical therapy, massages, osteopathy, and passive motion were initiated. At week 6, he completed his first functional movement screen; the score was 16/21 with no pain and no swelling. At week 8, the isokinetic test showed a 23% differential deficit between the two legs in maximum strength (at 90°/s). At week 10, he improved to 15% of injury-induced deficit which suggested he was ready to start running. At week 12, the athlete sustained his first threshold test. At week 16, he performed his first return to sports movement assessment, which revealed a 10% stronger difference between the legs. At week 16, he had his second threshold test. At week 17, his first on-field test revealed a 5% differential deficit between the two legs in the hop test. At week 18, isokinetic test demonstrates that the uninjured leg was 7% stronger than the recovering leg in maximum strength (at 90°/s). At week 20, his second on-field test revealed a 2% difference in hop test; at week 21, his third isokinetic test demonstrated a difference of 5% in maximum strength (at 90°/s). At week 21, he performed his second return to sports movement assessment which revealed a 2% difference between the limbs. Since it was the end of the championship, the team asked him to partake in the playoffs; moreover the player was very motivated to participate in the playoffs also because he was the captain of the team. Together with the player and the team, we decided to let him play even though we were aware of a heightened risk of injury than what is reported in the literature because of two factors: biological recovery times and the results of the tests we performed. In the decision making process about the athlete’s recovery time, it is important to balance the information available from the literature with the desires of the patient to avoid frustration.

Keywords: ACL, football, rehabilitation, return to play

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302 Reflections on the Trajectory of an Online Literature Cafe through Its Music and Arts Activities

Authors: Mariko Hara, Mari Aoki, Takako Ito, Masao Sugita

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Social distancing measures due to the COVID-19 crisis had a severe impact on music and art practices based in community settings. They had to re-think how to connect with their dispersed community using online tools. As the social distancing continues, there is an urgent need to investigate the possibilities of online community music and art practices. Are they sustainable actions that can have positive impacts on the community and the quality of lives of people over time? The Online Lindgren Café (hereafter ‘OLC’) is a monthly online literature event which started in June 2020. In the OLC, up to 14 members meet online to discuss the works of Astrid Lindgren and similar authors. Members come from various places in Japan and Norway, with a variety of expertise from music therapy, music education, psychotherapy, music sociology, storytelling, and theatre, and their family members join them. In these meetings, music and arts activities emerged in response to interests among the members. The resources and experiences of the members helped to develop these activities further. This paper first introduces one of the music and art activities in one specific event, a collaborative picture book-making with music, which was initiated and led by the second author. The third author chose the music, and the activity itself was recorded. This is followed by the description of a reflecting event, where the recording of the collaborative picture book-making activity was shared to facilitate further creations (drawings, haiku, and fabric weaving) as well as group reflections on the trajectories of the Online Lindgren Café. Finally, we will discuss the preliminary findings using the data collected at the reflecting event. Key findings suggest that the resource-driven approach of the OLC leveled the relationships among the intergenerational, multi-cultural, and interdisciplinary members. This enabled the members to set aside their professional and/or predominant identities, which allowed them to discover their own and others’ resources. The relaxed, unstructured, and liminal phenomenon at OLC can be regarded as a form of communitas, where members gain a sense of liberation and belonging in a different way from in-person communications. Participation from one’s home, as well as a video conferencing function that allowed the members to position themselves among the other participants in equal-sized windows, seems to have enabled members to feel safe to express themselves openly at the same time feel a sense of belonging. Furthermore, in the OLC, music and arts activities acted to inclusively connect and re-connect dispersed, intergenerational members with each other. For instance, in a music and drawing activity, music acted as a means for each member to engage in their own ‘drawing space’ while still feeling connected with the others. The positive experiences from these activities inspired the members to use similar approaches outside of the OLC. The finding suggests that, because of its resource-driven approach supported by the music and arts activities, the OLC could be developed further as a permeable and sustainable action even after any current social distancing measures are lifted.

Keywords: communitas, COVID-19, musical affordances, online community of practices, resource-driven approach

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301 Stimulus-Response and the Innateness Hypothesis: Childhood Language Acquisition of “Genie”

Authors: Caroline Kim

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Scholars have long disputed the relationship between the origins of language and human behavior. Historically, behaviorist psychologist B. F. Skinner argued that language is one instance of the general stimulus-response phenomenon that characterizes the essence of human behavior. Another, more recent approach argues, by contrast, that language is an innate cognitive faculty and does not arise from behavior, which might develop and reinforce linguistic facility but is not its source. Pinker, among others, proposes that linguistic defects arise from damage to the brain, both congenital and acquired in life. Much of his argument is based on case studies in which damage to the Broca’s and Wernicke’s areas of the brain results in loss of the ability to produce coherent grammatical expressions when speaking or writing; though affected speakers often utter quite fluent streams of sentences, the words articulated lack discernible semantic content. Pinker concludes on this basis that language is an innate component of specific, classically language-correlated regions of the human brain. Taking a notorious 1970s case of linguistic maladaptation, this paper queries the dominant materialist paradigm of language-correlated regions. Susan “Genie” Wiley was physically isolated from language interaction in her home and beaten by her father when she attempted to make any sort of sound. Though without any measurable resulting damage to the brain, Wiley was never able to develop the level of linguistic facility normally achieved in adulthood. Having received a negative reinforcement of language acquisition from her father and lacking the usual language acquisition period, in adulthood Wiley was able to develop language only at a quite limited level in later life. From a contemporary behaviorist perspective, this case confirms the possibility of language deficiency without brain pathology. Wiley’s potential language-determining areas in the brain were intact, and she was exposed to language later in her life, but she was unable to achieve the normal level of communication skills, deterring socialization. This phenomenon and others like it in the case limited literature on linguistic maladaptation pose serious clinical, scientific, and indeed philosophical difficulties for both of the major competing theories of language acquisition, innateness, and linguistic stimulus-response. The implications of such cases for future research in language acquisition are explored, with a particular emphasis on the interaction of innate capacity and stimulus-based development in early childhood.

Keywords: behaviorism, innateness hypothesis, language, Susan "Genie" Wiley

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300 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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299 The Acquisition of Spanish L4 by Learners with Croatian L1, English L2 and Italian L3

Authors: Barbara Peric

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The study of acquiring a third and additional language has garnered significant focus within second language acquisition (SLA) research. Initially, it was commonly viewed as merely an extension of second language acquisition (SLA). However, in the last two decades, numerous researchers have emphasized the need to recognize the unique characteristics of third language acquisition (TLA). This recognition is crucial for understanding the intricate cognitive processes that arise from the interaction of more than two linguistic systems in the learner's mind. This study investigates cross-linguistic influences in the acquisition of Spanish as a fourth language by students who have Croatian as a first language (L1). English as a second language (L2), and Italian as a third language (L3). Observational data suggests that influence or transfer of linguistic elements can arise not only from one's native language (L1) but also from non-native languages. This implies that, for individuals proficient in multiple languages, the native language doesn't consistently hold a superior position. Instead, it should be examined alongside other potential sources of linguistic transfer. Earlier studies have demonstrated that high proficiency in a second language can significantly impact cross-linguistic influences when acquiring a third and additional language. Among the extensively examined factors, the typological relationship stands out as one of the most scrutinized variables. The goal of the present study was to explore whether language typology and formal similarity or proficiency in the second language had a more significant impact on L4 acquisition. Participants in this study were third-year undergraduate students at Rochester Institute of Technology’s subsidiary in Croatia (RIT Croatia). All the participants had exclusively Croatian as L1, English as L2, Italian as L3 and were learning Spanish as L4 at the time of the study. All the participants had a high level of proficiency in English and low level of proficiency in Italian. Based on the error analysis the findings indicate that for some types of lexical errors such as coinage, language typology had a more significant impact and Italian language was the preferred source of transfer despite the law proficiency in that language. For some other types of lexical errors, such as calques, second language proficiency had a more significant impact, and English language was the preferred source of transfer. On the other hand, Croatian, Italian, and Spanish are more similar in the area of morphology due to higher degree of inflection compared to English and the strongest influence of the Croatian language was precisely in the area of morphology. The results emphasize the need to consider linguistic resemblances between the native language (L1) and the third and additional language as well as the learners' proficiency in the second language when developing successful teaching strategies for acquiring the third and additional language. These conclusions add to the expanding knowledge in the realm of Second Language Acquisition (SLA) and offer practical insights for language educators aiming to enhance the effectiveness of learning experiences in acquiring a third and additional language.

Keywords: third and additional language acquisition, cross-linguistic influences, language proficiency, language typology

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298 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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297 The Quantitative SWOT-Analysis of Service Blood Activity of Kazakhstan

Authors: Alua Massalimova

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Situation analysis of Blood Service revealed that the strengths dominated over the weak 1.4 times. The possibilities dominate over the threats by 1.1 times. It follows that by using timely the possibility the Service, it is possible to strengthen its strengths and avoid threats. Priority directions of the resulting analysis are the use of subjective factors, such as personal management capacity managers of the Blood Center in the field of possibilities of legal activity of administrative decisions and the mobilization of stable staff in general market conditions. We have studied for the period 2011-2015 retrospectively indicators of Blood Service of Kazakhstan. Strengths of Blood Service of RK(Ps4,5): 1) indicators of donations for 1000 people is higher than in some countries of the CIS (in Russia 14, Kazakhstan - 17); 2) the functioning science centre of transfusiology; 3) the legal possibility of additional financing blood centers in the form of paid services; 4) the absence of competitors; 5) training on specialty Transfusiology; 6) the stable management staff of blood centers, a high level of competence; 7) increase in the incidence requiring transfusion therapy (oncohematology); 8) equipment upgrades; 9) the opening of a reference laboratory; 10) growth of the proportion of issued high-quality blood components; 11) governmental organization 'Drop of Life'; 12) the functioning bone marrow register; 13) equipped with modern equipment HLA-laboratory; 14) High categorization of average medical workers; 15) availability of own specialized scientific journal; 16) vivarium. The weaknesses (Ps = 3.5): 1) the incomplete equipping of blood centers and blood transfusion cabinets according to standards; 2) low specific weight of paid services of the CC; 3) low categorization of doctors; 4) high staff turnover; 5) the low scientific potential of industrial and clinical of transfusiology; 6) the low wages paid; 7) slight growth of harvested donor blood; 8) the weak continuity with offices blood transfusion; 9) lack of agitation work; 10) the formally functioning of Transfusion Association; 11) the absence of scientific laboratories; 12) high standard deviation from the average for donations in the republic. The possibilities (Ps = 2,7): 1): international grants; 2) organization of international seminars on clinical of transfusiology; 3) cross-sectoral cooperation; 4) to increase scientific research in the field of clinical of transfusiology; 5) reduce the share of donation unsuitable for transfusion and processing; 6) strengthening marketing management in the development of fee-based services; 7) advertising paid services; 8) strengthening the publishing of teaching aids; 9) team-building staff. The threats (Ps = 2.1): 1) an increase of staff turnover; 2) the risk of litigation; 3) reduction gemoprodukts based on evidence-based medicine; 4) regression of scientific capacity; 5) organization of marketing; 6) transfusiologist marketing; 7) reduction in the quality of the evidence base transfusions.

Keywords: blood service, healthcare, Kazakhstan, quantative swot analysis

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296 21st Century Computer Technology for the Training of Early Childhood Teachers: A Study of Second-Year Education Students Challenged with Building a Kindergarten Website

Authors: Yonit Nissim, Eyal Weissblueth

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This research is the continuation of a process that began in 2010 with the goal of redesigning the training program for future early childhood teachers at the Ohalo College, to integrate technology and provide 21st-century skills. The article focuses on a study of the processes involved in developing a special educational unit which challenged students with the task of designing, planning and building an internet site for kindergartens. This project was part of their second-year studies in the early childhood track of an interdisciplinary course entitled 'Educating for the Future.' The goal: enabling students to gain experience in developing an internet site specifically for kindergartens, and gain familiarity with Google platforms, the acquisition and use of innovative skills and the integration of technology in pedagogy. Research questions examined how students handled the task of building an internet site. The study explored whether the guided process of building a site helped them develop proficiency in creativity, teamwork, evaluation and learning appropriate to the 21st century. The research tool was a questionnaire constructed by the researchers and distributed online to the students. Answers were collected from 50-course participants. Analysis of the participants’ responses showed that, along with the significant experience and benefits that students gained from building a website for kindergarten, ambivalence was shown toward the use of new, unfamiliar and complex technology. This attitude was characterized by unease and initial emotional distress triggered by the departure from routine training to an island of uncertainty. A gradual change took place toward the adoption of innovation with the help of empathy, training, and guidance from the instructors, leading to the students’ success in carrying out the task. Initial success led to further successes, resulting in a quality product and a feeling of personal competency among the students. A clear and extreme emotional shift was observed on the spectrum from a sense of difficulty and dissatisfaction to feelings of satisfaction, joy, competency and cognitive understanding of the importance of facing a challenge and succeeding. The findings of this study can contribute to increased understanding of the complex training process of future kindergarten teachers, coping with a changing world, and pedagogy that is supported by technology.

Keywords: early childhood teachers, educating for the future, emotions, kindergarten website

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295 Early Childhood Education and Learning Outcomes in Lower Primary Schools, Uganda

Authors: John Acire, Wilfred Lajul, Ogwang Tom

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Using a qualitative research technique, this study investigates the influence of Early Childhood Education (ECE) on learning outcomes in lower primary schools in Gulu City, Uganda. The study, which is based on Vygotsky's sociocultural theory of human learning, fills gaps in the current literature on the influence of ECE on learning outcomes. The aims of the study include analyzing the state of learning outcomes, investigating ECE practices, and determining the influence of these practices on learning outcomes in lower primary schools. The findings highlight the critical significance of ECE in promoting children's overall development. Nursery education helps children improve their handwriting, reading abilities, and general cognitive development. Children who have received nursery education have improved their abilities to handle pencils, form letters, and engage in social interactions, highlighting the significance of fine motor skills and socializing. Despite the good elements, difficulties in implementing ECE practices were found, such as differences in teaching styles, financial limits, and potential weariness due to prolonged school hours. The study suggests focused interventions to improve the effectiveness of ECE practices, ensure their connection with educational goals and maximize their influence on children's development. The study's findings show that respondents agree on the importance of nursery education in supporting holistic development, socialization, language competency, and conceptual comprehension. Challenges in nursery education, such as differences in teaching techniques and insufficient resources, highlight the need for comprehensive measures to address these challenges. Furthermore, parental engagement in home learning activities was revealed as an important factor affecting early education outcomes. Children who were engaged at home performed better in lower primary, emphasizing the value of a supportive family environment. Finally, the report suggests measures to enhance parental participation, changes in teaching methods through retraining, and age-appropriate enrolment. Future studies might concentrate on the involvement of parents, ECE policy practice, and the influence of ECE teachers on lower primary school learning results. These ideas are intended to help create a more favorable learning environment by encouraging holistic development and preparing children for success in succeeding academic levels.

Keywords: early childhood education, learning outcomes in lower primary schools, early childhood education practices, how ECE practices influence learning outcomes in lower primary schools

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294 Real-Time Neuroimaging for Rehabilitation of Stroke Patients

Authors: Gerhard Gritsch, Ana Skupch, Manfred Hartmann, Wolfgang Frühwirt, Hannes Perko, Dieter Grossegger, Tilmann Kluge

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Rehabilitation of stroke patients is dominated by classical physiotherapy. Nowadays, a field of research is the application of neurofeedback techniques in order to help stroke patients to get rid of their motor impairments. Especially, if a certain limb is completely paralyzed, neurofeedback is often the last option to cure the patient. Certain exercises, like the imagination of the impaired motor function, have to be performed to stimulate the neuroplasticity of the brain, such that in the neighboring parts of the injured cortex the corresponding activity takes place. During the exercises, it is very important to keep the motivation of the patient at a high level. For this reason, the missing natural feedback due to a movement of the effected limb may be replaced by a synthetic feedback based on the motor-related brain function. To generate such a synthetic feedback a system is needed which measures, detects, localizes and visualizes the motor related µ-rhythm. Fast therapeutic success can only be achieved if the feedback features high specificity, comes in real-time and without large delay. We describe such an approach that offers a 3D visualization of µ-rhythms in real time with a delay of 500ms. This is accomplished by combining smart EEG preprocessing in the frequency domain with source localization techniques. The algorithm first selects the EEG channel featuring the most prominent rhythm in the alpha frequency band from a so-called motor channel set (C4, CZ, C3; CP6, CP4, CP2, CP1, CP3, CP5). If the amplitude in the alpha frequency band of this certain electrode exceeds a threshold, a µ-rhythm is detected. To prevent detection of a mixture of posterior alpha activity and µ-activity, the amplitudes in the alpha band outside the motor channel set are not allowed to be in the same range as the main channel. The EEG signal of the main channel is used as template for calculating the spatial distribution of the µ - rhythm over all electrodes. This spatial distribution is the input for a inverse method which provides the 3D distribution of the µ - activity within the brain which is visualized in 3D as color coded activity map. This approach mitigates the influence of lid artifacts on the localization performance. The first results of several healthy subjects show that the system is capable of detecting and localizing the rarely appearing µ-rhythm. In most cases the results match with findings from visual EEG analysis. Frequent eye-lid artifacts have no influence on the system performance. Furthermore, the system will be able to run in real-time. Due to the design of the frequency transformation the processing delay is 500ms. First results are promising and we plan to extend the test data set to further evaluate the performance of the system. The relevance of the system with respect to the therapy of stroke patients has to be shown in studies with real patients after CE certification of the system. This work was performed within the project ‘LiveSolo’ funded by the Austrian Research Promotion Agency (FFG) (project number: 853263).

Keywords: real-time EEG neuroimaging, neurofeedback, stroke, EEG–signal processing, rehabilitation

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293 Promoting Patients' Adherence to Home-Based Rehabilitation: A Randomised Controlled Trial of a Theory-Driven Mobile Application

Authors: Derwin K. C. Chan, Alfred S. Y. Lee

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The integrated model of self-determination theory and the theory of planned behaviour has been successfully applied to explain individuals’ adherence to health behaviours, including behavioural adherence toward rehabilitation. This study was a randomised controlled trial that examined the effectiveness of an mHealth intervention (i.e., mobile application) developed based on this integrated model in promoting treatment adherence of patients of anterior cruciate ligament rupture during their post-surgery home-based rehabilitation period. Subjects were 67 outpatients (aged between 18 and 60) who undertook anterior cruciate ligament (ACL) reconstruction surgery for less than 2 months for this study. Participants were randomly assigned either into the treatment group (who received the smartphone application; N = 32) and control group (who receive standard treatment only; N = 35), and completed psychological measures relating to the theories (e.g., motivations, social cognitive factors, and behavioural adherence) and clinical outcome measures (e.g., subjective knee function (IKDC), laxity (KT-1000), muscle strength (Biodex)) relating to ACL recovery at baseline, 2-month, and 4-month. Generalise estimating equation showed the interaction between group and time was significant on intention was only significant for intention (Wald x² = 5.23, p = .02), that of perceived behavioural control (Wald x² = 3.19, p = .07), behavioural adherence (Wald x² = 3.08, p = .08, and subjective knee evaluation (Wald x² = 2.97, p = .09) were marginally significant. Post-hoc between-subject analysis showed that control group had significant drop of perceived behavioural control (p < .01), subjective norm (p < .01) and intention (p < .01), behavioural adherence (p < .01) from baseline to 4-month, but such pattern was not observed in the treatment group. The treatment group had a significant decrease of behavioural adherence (p < .05) in the 2-month, but such a decrease was not observed in 4-month (p > .05). Although the subjective knee evaluation in both group significantly improved at 2-month and 4-month from the baseline (p < .05), and the improvements in the control group (mean improvement at 4-month = 40.18) were slightly stronger than the treatment group (mean improvement at 4-month = 34.52). In conclusion, the findings showed that the theory driven mobile application ameliorated the decline of treatment intention of home-based rehabilitation. Patients in the treatment group also reported better muscle strength than control group at 4-month follow-up. Overall, the mobile application has shown promises on tackling the problem of orthopaedics outpatients’ non-adherence to medical treatment.

Keywords: self-determination theory, theory of planned behaviour, mobile health, orthopaedic patients

Procedia PDF Downloads 194
292 Emergency Surgery in the Elderly, What Particularities

Authors: Mekroud Amel

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Introduction The rate of use by the elderly of emergency departments, operating rooms and intensive care units has increased worldwide. Emergency surgery is a context where evaluation is often insufficient, with incomplete information gathering. The aim of this work is to shed light on the frequent use of emergency surgeries by the elderly and their characteristics, as well as on the lack of geriatric assessment scores in the emergency room. Material : Prospective, observational and descriptive, monocentric study. Patients aged 65 and over, admitted for emergency surgery in the operating room, were counted. Emergency operating room including visceral surgery, urology, traumatology and neurosurgery. Parameters studied: Patient characteristics, degree of autonomy, type of surgical pathology, operative management times, preoperative evaluation, postoperative outcome Results : 192 patients were identified over 12 months, from 09.01.2017 to 08.31.2018 Age from 65 to 101 years, 79.81 years +/- 8.38. With predominance of the age group between [65-75 years] 41.1% Female predominance, Sexratio = 0.81 Elderly subjects with total motor autonomy are in the majority at 57.8% Subjects without pathological ATCD represent 12.5% of cases Those who are on only one type of medication or without any treatment are at 36.9% Discussion : The emergency operative care of the elderly patient for a surgical or traumatological pathology is characterized by many specificities linked first to the emergency context, where the evaluation is often insufficient, besides the fact that the elderly patient has particularities requiring reception in centers with experience in the care of this category of patient, or, failing that, a center which uses the minimum of geriatric evaluation scores which are simplified for the emergency departments. In our hospital, we have not yet made this evaluation routine in the emergency room and this delay in the introduction of these scores can be directly attributed to the covid 19 pandemic. Besides the standard preoperative assessment, only 43.2% of patients were assessed in the preoperative period by an anesthesiologist. Traumatological emergencies come first 68.2% followed by visceral emergencies 19.2% (including proctological, urological emergencies), neurosurgical emergencies 7.8% and finally peripheral emergency surgery all acts combined 4.7%. Hospital stay at 9.6 +/- 16.8 days, average operability time of 4.5 +/- 3 days. Death rate at 7.29% Conclusion This work has demonstrated the major impact of emergency surgery, which remains curable for the most part, on the elderly patient despite total motor and cognitive autonomy preoperatively. The improvement of the preoperative evaluation, the reduction of the operating time and enhanced recovery after surgery, with personalized protocols, are the only guarantee for the resumption of preoperative autonomy in these patients.

Keywords: emergency surgery, elderly patients, preoperative geriatric scores, curable emergency surgical pathologies

Procedia PDF Downloads 74
291 Diagnosis, Treatment, and Prognosis in Cutaneous Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: A Narrative Review Apropos of a Case

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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290 Auditory Perception of Frequency-Modulated Sweeps and Reading Difficulties in Chinese

Authors: Hsiao-Lan Wang, Chun-Han Chiang, I-Chen Chen

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In Chinese Mandarin, lexical tones play an important role to provide contrasts in word meaning. They are pitch patterns and can be quantified as the fundamental frequency (F0), expressed in Hertz (Hz). In this study, we aim to investigate the influence of frequency discrimination on Chinese children’s performance of reading abilities. Fifty participants from 3rd to 4th grades, including 24 children with reading difficulties and 26 age-matched children, were examined. A serial of cognitive, language, reading and psychoacoustic tests were administrated. Magnetoencephalography (MEG) was also employed to study children’s auditory sensitivity. In the present study, auditory frequency was measured through slide-up pitch, slide-down pitch and frequency-modulated tone. The results showed that children with Chinese reading difficulties were significantly poor at phonological awareness and auditory discrimination for the identification of frequency-modulated tone. Chinese children’s character reading performance was significantly related to lexical tone awareness and auditory perception of frequency-modulated tone. In our MEG measure, we compared the mismatch negativity (MMNm), from 100 to 200 ms, in two groups. There were no significant differences between groups during the perceptual discrimination of standard sounds, fast-up and fast-down frequencies. However, the data revealed significant cluster differences between groups in the slow-up and slow-down frequencies discrimination. In the slow-up stimulus, the cluster demonstrated an upward field map at 106-151 ms (p < .001) with a strong peak time at 127ms. The source analyses of two dipole model and localization resolution model (CLARA) from 100 to 200 ms both indicated a strong source from the left temporal area with 45.845% residual variance. Similar results were found in the slow-down stimulus with a larger upward current at 110-142 ms (p < 0.05) and a peak time at 117 ms in the left temporal area (47.857% residual variance). In short, we found a significant group difference in the MMNm while children processed frequency-modulated tones with slow temporal changes. The findings may imply that perception of sound frequency signals with slower temporal modulations was related to reading and language development in Chinese. Our study may also support the recent hypothesis of underlying non-verbal auditory temporal deficits accounting for the difficulties in literacy development seen developmental dyslexia.

Keywords: Chinese Mandarin, frequency modulation sweeps, magnetoencephalography, mismatch negativity, reading difficulties

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289 A Case of Borderline Personality Disorder: An Explanatory Study of Unconscious Conflicts through Dream-Analysis

Authors: Mariam Anwaar, Kiran B. Ahmad

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Borderline Personality Disorder (BPD) is an invasive presence of affect instability, disturbance in self-concept and attachment in relationships. The profound indicator is the dichotomous approach of the world in which the ego categorizes individuals, especially their significant others, into secure or threatful beings, leaving little room for a complex combination of characteristics in one person. This defense mechanism of splitting their world has been described through the explanatory model of unconscious conflict theorized by Sigmund Freud’s Electra Complex in the Phallic Stage. The central role is of the father with whom the daughter experiences penis envy, thus identifying with the mother’s characteristics to receive the father’s attention. However, Margret Mahler, an object relation theorist, elucidates the central role of the mother and that the split occurs during the pre-Electra complex stage. Amid the 14 and 24 months of the infant, it acknowledges the world away from the mother as they have developed milestones such as crawling. In such novelty, the infant crawls away from the mother creating a sense of independence (individuation). On the other hand, being distant causes anxiety, making them return to their original object of security (separation). In BPD, the separation-individuation stage is disrupted, due to contradictory actions of the caregiver, which results in splitting the object into negative and positive aspects, repressing the former and adhering to the latter for survival. Thus, with time, the ego distorts the reality into dichotomous categories, using the splitting defenses, and the mental representation of the self is distorted due to the internalization of the negative objects. The explanatory model was recognized in the case study of Fizza, at 21-year-old Pakistani female, residing in Karachi. Her marital status is single with an occupation being a dental student. Fizza lives in a nuclear family but is surrounded by her extended family as they all are in close vicinity. She came with the complaints of depressive symptoms for two-years along with self-harm due to severe family conflicts. Through the intervention of Dialectical Behavior Therapy (DBT), the self-harming actions were reduced, however, this libidinal energy transformed into claustrophobic symptoms and, along with this, Fizza has always experienced vivid dreams. A retrospective method of Jungian dream-analysis was applied to locate the origins of the splitting in the unconscious. The result was the revelation of a sexual harassment trauma at the age of six-years which was displaced in the form of self-harm. In addition to this, the presence of a conflict at the separation-individuation stage was detected during the dream-analysis, and it was the underlying explanation of the claustrophobic symptoms. This qualitative case study implicates the use of a patient’s subjective experiences, such as dreams, to journey through the spiral of the unconscious in order to not only detect repressed memories but to use them in psychotherapy as a means of healing the patient.

Keywords: borderline personality disorder, dream-analysis, Electra complex, separation-individuation, splitting, unconscious

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288 A Post-Occupancy Evaluation of the Impact of Indoor Environmental Quality on Health and Well-Being in Office Buildings

Authors: Suyeon Bae, Abimbola Asojo, Denise Guerin, Caren Martin

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Post-occupancy evaluations (POEs) have been recognized for documenting occupant well-being and responses to indoor environmental quality (IEQ) factors such as thermal, lighting, and acoustic conditions. Sustainable Post-Occupancy evaluation survey (SPOES) developed by an interdisciplinary team at a Midwest University provides an evidence-based quantitative analysis of occupants’ satisfaction in office, classroom, and residential spaces to help direct attention to successful areas and areas that need improvement in buildings. SPOES is a self-administered and Internet-based questionnaire completed by building occupants. In this study, employees in three different office buildings rated their satisfaction on a Likert-type scale about 12 IEQ criteria including thermal condition, indoor air quality, acoustic quality, daylighting, electric lighting, privacy, view conditions, furnishings, appearance, cleaning and maintenance, vibration and movement, and technology. Employees rated their level of satisfaction on a Likert-type scale from 1 (very dissatisfied) to 7 (very satisfied). They also rate the influence of their physical environment on their perception of their work performance and the impact of their primary workspaces on their health on a scale from 1 (hinders) to 7 (enhances). Building A is a three-story building that includes private and group offices, classrooms, and conference rooms and amounted to 55,000 square-feet for primary workplace (N=75). Building B, a six-story building, consisted of private offices, shared enclosed office, workstations, and open desk areas for employees and amounted to 14,193 square-feet (N=75). Building C is a three-story 56,000 square-feet building that included classrooms, therapy rooms, an outdoor playground, gym, restrooms, and training rooms for clinicians (N=76). The results indicated that 10 IEQs for Building A except acoustic quality and privacy showed statistically significant correlations on the impact of the primary workspace on health. In Building B, 11 IEQs except technology showed statistically significant correlations on the impact of the primary workspace on health. Building C had statistically significant correlations between all 12 IEQ and the employees’ perception of the impact of their primary workspace on their health in two-tailed correlations (P ≤ 0.05). Out of 33 statistically significant correlations, 25 correlations (76%) showed at least moderate relationship (r ≥ 0.35). For the three buildings, daylighting, furnishings, and indoor air quality IEQs ranked highest on the impact on health. IEQs about vibration and movement, view condition, and electric lighting ranked second, followed by IEQs about cleaning and maintenance and appearance. These results imply that 12 IEQs developed in SPOES are highly related to employees’ perception of how their primary workplaces impact their health. The IEQs in this study offer an opportunity for improving occupants’ well-being and the built environment.

Keywords: post-occupancy evaluation, built environment, sustainability, well-being, indoor air quality

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287 The Effects of Collaborative Videogame Play on Flow Experience and Mood

Authors: Eva Nolan, Timothy Mcnichols

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Gamers spend over 3 billion hours collectively playing video games a week, which is arguably not nearly enough time to indulge in the many benefits gaming has to offer. Much of the previous research on video gaming is centered on the effects of playing violent video games and the negative impacts they have on the individual. However, there is a dearth of research in the area of non-violent video games, specifically the emotional and cognitive benefits playing non-violent games can offer individuals. Current research in the area of video game play suggests there are many benefits to playing for an individual, such as decreasing symptoms of depression, decreasing stress, increasing positive emotions, inducing relaxation, decreasing anxiety, and particularly improving mood. One suggestion as to why video games may offer such benefits is that they possess ideal characteristics to create and maintain flow experiences, which in turn, is the subjective experience where an individual obtains a heightened and improved state of mind while they are engaged in a task where a balance of challenge and skill is found. Many video games offer a platform for collaborative gameplay, which can enhance the emotional experience of gaming through the feeling of social support and social inclusion. The present study was designed to examine the effects of collaborative gameplay and flow experience on participants’ perceived mood. To investigate this phenomenon, an in-between subjects design involving forty participants were randomly divided into two groups where they engaged in solo or collaborative gameplay. Each group represented an even number of frequent gamers and non-frequent gamers. Each participant played ‘The Lego Movie Videogame’ on the Playstation 4 console. The participant’s levels of flow experience and perceived mood were measured by the Flow State Scale (FSS) and the Positive and Negative Affect Schedule (PANAS). The following research hypotheses were investigated: (i.) participants in the collaborative gameplay condition will experience higher levels of flow experience and higher levels of mood than those in the solo gameplay condition; (ii.) participants who are frequent gamers will experience higher levels of flow experience and higher levels of mood than non-frequent gamers; and (iii.) there will be a significant positive relationship between flow experience and mood. If the estimated findings are supported, this suggests that engaging in collaborative gameplay can be beneficial for an individual’s mood and that experiencing a state of flow can also enhance an individual’s mood. Hence, collaborative gaming can be beneficial to promote positive emotions (higher levels of mood) through engaging an individual’s flow state.

Keywords: collaborative gameplay, flow experience, mood, games, positive emotions

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286 Safety of Mesenchymal Stem Cells Therapy: Potential Risk of Spontaneous Transformations

Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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285 Characterization and Evaluation of the Dissolution Increase of Molecular Solid Dispersions of Efavirenz

Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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284 A Brief Review on Doping in Sports and Performance-Enhancing Drugs

Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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283 Strengthening Social and Psychological Resources - Project "Herausforderung" as a (Sports-) Pedagogical Concept in Adolescence

Authors: Kristof Grätz

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Background: Coping with crisis situations (e.g., the identity crisis in adolescence) is omnipresent in today's socialization and should be encouraged as a child. For this reason, students should be given the opportunity to create, endure and manage these crisis situations in a sporting context within the project “Herausforderung.” They should prove themselves by working on a self-assigned task, accompanied by ‚coaches’ in a place outside of their hometown. The aim of the project is to observe this process from a resource-oriented perspective. Health promotion, as called for by the WHO in the Ottawa Charter since 1986, includes strengthening psychosocial resources. These include cognitive, emotional, and social potentials that contribute to improving the quality of life, provide favourable conditions for coping with health burdens and enable people to influence their physical performance and well-being self-confidently and actively. A systematic strengthening of psychosocial resources leads to an improvement in mental health and contributes decisively to the regular implementation and long-term maintenance of this health behavior. Previous studies have already shown significant increases in self-concept following experiential educational measures [Fengler, 2007; Eberle & Fengler, 2018] and positive effects of experience-based school trips on the social competence of students [Reuker, 2009]. Method: The research project examines the influence of the project “Herausforderung” on psychosocial resources such as self-efficacy, self-concept, social support, and group cohesion. The students participating in the project will be tested in a pre-post design in the context of the challenge. This test includes specific questions to capture the different psychosocial resources. For the measurement, modifications of existing scales with good item selectivity and reliability are used to a large extent, so that acceptable item and scale values can be expected. If necessary, the scales were adapted or shortened to the specific context in order to ensure a balanced relationship between reliability and test economy. Specifically, these are already tested scales such as FRKJ 8-16, FSKN, GEQ, and F-SozU. The aim is to achieve a sample size of n ≥ 100. Conclusion: The project will be reviewed with regard to its effectiveness, and implications for a resource-enhancing application in sports settings will be given. Conclusions are drawn as to which extent to specific experiential educational content in physical education can have a health-promoting effect on the participants.

Keywords: children, education, health promotion, psychosocial resources

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282 The Disease That 'Has a Woman Face': Feminization of HIV/AIDS in Nagaland, North-East India

Authors: Kitoholi V. Zhimo

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Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

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281 Attention States in the Sustained Attention to Response Task: Effects of Trial Duration, Mind-Wandering and Focus

Authors: Aisling Davies, Ciara Greene

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Over the past decade the phenomenon of mind-wandering in cognitive tasks has attracted widespread scientific attention. Research indicates that mind-wandering occurrences can be detected through behavioural responses in the Sustained Attention to Response Task (SART) and several studies have attributed a specific pattern of responding around an error in this task to an observable effect of a mind-wandering state. SART behavioural responses are also widely accepted as indices of sustained attention and of general attention lapses. However, evidence suggests that these same patterns of responding may be attributable to other factors associated with more focused states and that it may also be possible to distinguish the two states within the same task. To use behavioural responses in the SART to study mind-wandering, it is essential to establish both the SART parameters that would increase the likelihood of errors due to mind-wandering, and exactly what type of responses are indicative of mind-wandering, neither of which have yet been determined. The aims of this study were to compare different versions of the SART to establish which task would induce the most mind-wandering episodes and to determine whether mind-wandering related errors can be distinguished from errors during periods of focus, by behavioural responses in the SART. To achieve these objectives, 25 Participants completed four modified versions of the SART that differed from the classic paradigm in several ways so to capture more instances of mind-wandering. The duration that trials were presented for was increased proportionately across each of the four versions of the task; Standard, Medium Slow, Slow, and Very Slow and participants intermittently responded to thought probes assessing their level of focus and degree of mind-wandering throughout. Error rates, reaction times and variability in reaction times decreased in proportion to the decrease in trial duration rate and the proportion of mind-wandering related errors increased, until the Very Slow condition where the extra decrease in duration no longer had an effect. Distinct reaction time patterns around an error, dependent on level of focus (high/low) and level of mind-wandering (high/low) were also observed indicating four separate attention states occurring within the SART. This study establishes the optimal duration of trial presentation for inducing mind-wandering in the SART, provides evidence supporting the idea that different attention states can be observed within the SART and highlights the importance of addressing other factors contributing to behavioural responses when studying mind-wandering during this task. A notable finding in relation to the standard SART, was that while more errors were observed in this version of the task, most of these errors were during periods of focus, raising significant questions about our current understanding of mind-wandering and associated failures of attention.

Keywords: attention, mind-wandering, trial duration rate, Sustained Attention to Response Task (SART)

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280 Effects of an Envious Experience on Schadenfreude and Economic Decisions Making

Authors: Pablo Reyes, Vanessa Riveros Fiallo, Cesar Acevedo, Camila Castellanos, Catalina Moncaleano, Maria F. Parra, Laura Colmenares

Abstract:

Social emotions are physiological, cognitive and behavioral phenomenon that intervene in the mechanisms of adaptation of individuals and their context. These are mediated by interpersonal relationship and language. Such emotions are subdivided into moral and comparison. The present research emphasizes two comparative emotions: Envy and Schadenfreude. Envy arises when a person lack of quality, possessions or achievements and these are superior in someone else. The Schadenfreude (SC) expresses the pleasure that someone experienced by the misfortune of the other. The relationship between both emotions has been questioned before. Hence there are reports showing that envy increases and modulates SC response. Other documents suggest that envy causes SC response. However, the methodological approach of the topic has been made through self-reports, as well as the hypothetical scenarios. Given this problematic, the neuroscience social framework provides an alternative and demonstrates that social emotions have neurophysiological correlates that can be measured. This is relevant when studying social emotions that are reprehensible like envy or SC are. When tested, the individuals tend to report low ratings due to social desirability. In this study, it was drawn up a proposal in research's protocol and the progress on its own piloting. The aim is to evaluate the effect of feeling envy and Schadenfreude has on the decision-making process, as well as the cooperative behavior in an economic game. To such a degree, it was proposed an experimental model that will provoke to feel envious by performing games against an unknown opponent. The game consists of asking general knowledge questions. The difficulty level in questions and the strangers' facial response have been manipulated in order to generate an ecological comparison framework and be able to arise both envy and SC emotions. During the game, an electromyography registry will be made for two facial muscles that have been associated with the expressiveness of envy and SC emotions. One of the innovations of the current proposal is the measurement of the effect that emotions have on a specific behavior. To that extent, it was evaluated the effect of each condition on the dictators' economic game. The main intention is to evaluate if a social emotion can modulate actions that have been associated with social norms, in the literacy. The result of the evaluation of a pilot model (without electromyography record and self-report) have shown an association between envy and SC, in a way that as the individuals report a greater sense of envy, the greater the chance to experience SC. The results of the economic game show a slight tendency towards profit maximization decisions. It is expected that at the time of using real cash this behavior will be strengthened and also to correlate with the responses of electromyography.

Keywords: envy, schadenfreude, electromyography, economic games

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279 Safety of Implementation the Gluten - Free Diet in Children with Autism Spectrum Disorder

Authors: J. Jessa

Abstract:

Background: Autism is a pervasive developmental disorder, the incidence of which has significantly increased in recent years. Children with autism have impairments in social skills, communication, and imagination. Children with autism has more common than healthy children feeding problems: food selectivity, problems with gastrointestinal tract: diarrhea, constipations, abdominal pain, reflux and others. Many parents of autistic children report that after implementation of gluten-, casein- and sugar free diet those symptoms disappear and even cognitive functions become better. Some children begin to understand speech and to communicate with parents, regain eye contact, become more calm, sleep better and has better concentration. Probably at the root of this phenomenon lies elimination from the diet peptides construction of which is similar to opiates. Enhanced permeability of gut causes absorption of not fully digested opioid-like peptides from food, like gluten and casein and probably others (proteins from soy and corn) which impact on brain of autistic children. Aim of the study: The aim of the study is to assess the safety of gluten-free diet in children with autism, aged 2,5-7. Methods: Participants of the study (n=70) – children aged 2,5-7 with autism are divided into 3 groups. The first group (research group) are patients whose parents want to implement a gluten-free diet. The second group are patients who have been recommended to eliminate from the diet artificial substances, such as preservatives, artificial colors and flavors, and others (control group 1). The third group (control group 2) are children whose parents did not agree for implementation of the diet. Caregivers of children on the diet are educated about the specifics of the diet and how to avoid malnutrition. At the start of the study we exclude celiac disease. Before the implementation of the diet we performe a blood test for patients (morphology, ferritin, total cholesterol, dry peripheral blood drops to detect some genetic metabolic diseases), plasma aminogram) and urine tests (excretion of ions: Mg, Na, Ca, the profile of organic acids in urine), which assess nutritional status as well as the psychological test assessing the degree of the child's psychological functioning (PEP-R). All of these tests will be repeated after one year from the implementation of the diet. Results: To the present moment we examined 42 children with autism. 12 of children are on gluten- free diet. Our preliminary results are promising. Parents of 9 of them report that, there is a big improvement in child behavior, concentration, less aggression incidents, better eye contact and better verbal skills. Conclusion: Our preliminary results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD.

Keywords: gluten free diet, autism spectrum disorder, autism, blood test

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278 Antimicrobial Activities of Lactic Acid Bacteria from Fermented Foods and Probiotic Products

Authors: Alec Chabwinja, Cannan Tawonezvi, Jerneja Vidmar, Constance Chingwaru, Walter Chingwaru

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Objective: To evaluate the potential of commercial fermented / probiotic products available in Zimbabwe or internationally, and strains of Lactobacillus plantarum (L. plantarum) as prophylaxis and therapy against diarrhoeal and sexually transmitted infections. Methods: The antimicrobial potential of cultures of lactobacilli enriched from 4 Zimbabwean commercial food/beverage products, namely Dairibord Lacto sour milk (DLSM), Probrand sour milk (PSM), Kefalos Vuka cheese (KVC) and Chibuku opaque beer (COB); three probiotic products obtainable in Europe and internationally; and four strains of L. plantarum obtained from Balkan traditional cheeses and Zimbabwean foods against clinical strains of Escherichia coli (E. coli) and non-clinical strains of Candida albicans and Rhodotorula spp. was assayed using the well diffusion method. Three commercial Agar diffusion assay and a competitive exclusion assay were carried out on Mueller-Hinton agar. Results: Crude cultures of putative lactobacillus strains obtained from Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer) exhibited significantly greater antimicrobial activities against clinical strains of E. coli than strains of L. plantarum isolated from Balkan cheeses (CLP1, CLP2 or CLP3) or crude microbial cultures from commercial paediatric probiotic products (BG, PJ and PL) of a culture of Lactobacillus rhamnosus LGG (p < 0.05). Furthermore, the following has high antifungal activities against the two yeasts: supernatant-free microbial pellet (SFMP) from an extract of M. azedarach leaves (27mm ± 2.5) > cell-free culture supernatants (CFCS) from Maaz Dairy sour milk and Mnandi sour milk (approximately 26mm ± 1.8) > CFCS and SFMP from Amansi hodzeko (25mm ± 1.5) > CFCS from Parinari curatellifolia fruit (24mm ± 1.5), SFMP from P. curatellifolia fruit (24mm ± 1.4) and SFMP from mahewu (20mm ± 1.5). These cultures also showed high tolerance to acidic conditions (~pH4). Conclusions: The putative lactobacilli from four commercial Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer), and three strains of L. plantarum from Balkan cheeses (CLP1, CLP2 or CLP3) exhibited high antibacterial activities, while Maaz Dairy sour-, Mnandi sour- and Amansi hodzeko milk products had high antifungal activities. Our selection of Zimbabwean probiotic products has potential for further development into probiotic products for use in the control diarrhea caused by pathogenic strains of E. coli or yeast infections. Studies to characterise the probiotic potential of the live cultures in the products are underway.

Keywords: lactic acid bacteria, Staphylococcus aureus, Streptococcus spp, yeast, inhibition, acid tolerance

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277 Effect of Endurance Training on Serum Chemerin Levels and Lipid Profile of Plasma in Obese Women

Authors: A. Moghadasein, M. Ghasemi, S. Fazelifar

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Aim: Chemerin is a novel adipokine that play an important role in regulating lipid metabolism and abiogenesis. Chemerin is dependent on autocrine and paracrine signals for the differentiation and maturation of fat cells; it also regulates glucose uptake in fat cells and stimulates lipolysis. It has been reported that in adipocytes, chemerin enhances the insulin-stimulated glucose and causes the phosphorylation of tyrosine in Insulin receptor substrate. According to the studies, Chemerin may increase insulin sensitivity in adipose tissue and is largely associated with Body mass index, triglycerides, and blood pressure in those with normal glucose tolerance. There is limited information available regarding the effect of exercise training on serum chemerin concentrations. The purpose of this study was to investigate the effect of endurance training on serum chemerin levels and lipids of plasma in overweight women. Methodology: This study was a quasi-experimental research with a pre-post test design. After required examination and verification of high pressure by the physician, 22 obese subjects (age: 35.64±5.55 yr, weight: 75.62±9.30 kg, body mass index: 32.4±1.6 kg/m2) were randomly assigned to aerobic training (n= 12) and control (n= 12) groups. Participants completed a questionnaire indicating the lack of sports history during the past six months, the lack of anti-hypertension drugs use, hormone therapy, cardiovascular problems, and complete stoppage of menstrual cycle. Aerobic training was performed 3 times weekly for 8 weeks. Resting levels of chemerin plasma, metabolic parameters were measured prior to and after the intervention. The control group did not participate in any training program. In this study, ethical considerations included the complete description of the objectives to the study participants, ensuring the confidentiality of their information. Kolmogorov-Smirnov and Levin test were used for determining the normal distribution of data and homogeneity of variances, respectively. Analyze of variance with repeated measure were used to investigate the changes in the intra-group and the differences in inter-group of variables. Statistical operations were performed using SPSS 16 and the significance level of the tests was considered at P < 0.05. Results: After an 8 week aerobic training, levels of chemerin plasma were significantly decreased in aerobic trained group when compared with their control groups (p < 0.05).Concurrently, levels of HDL-c were significantly decreased (p < 0.05) whereas, levels of cholesterol, TG and LDL-c, showed no significant changes (p > 0.05). No significant correlations between chemerin levels and weight loss were observed in subjects with overweight women. Conclusion: The present study demonstrated, 8 weeks aerobic training, reduced serum chemerin concentrations in overweight women. Whereas, aerobic training exercise programmers affected the lipid profile response of obese subjects differently. However further research is warranted in order to unravel the molecular mechanism for the range of responses and the role of serum chemerin.

Keywords: chemerin, aerobic training, lipid profile, obese women

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276 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade

Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

Abstract:

Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

Procedia PDF Downloads 141