Search results for: rational memory therapy

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Kangana Sengar, Sanjay Deb, Ramesh Dawar

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Introduction: Ki-67 can be a useful marker in determining proliferative activity in patients with multiple myeloma (MM). However, using Ki-67 alone results in the erroneous inclusion of non-myeloma cells leading to false high counts. We have used Dual IHC (immunohistochemistry) staining with Ki-67 and CD138 to enhance specificity in assessing proliferative activity of bone marrow plasma cells. Aims and objectives: To estimate the proportion of proliferating (Ki-67 expressing) plasma cells in patients with MM and correlation of Ki-67 with other known prognostic parameters. Materials and Methods: Fifty FFPE (formalin fixed paraffin embedded) blocks of trephine biopsies of cases diagnosed as MM from 2010 to 2015 are subjected to H & E staining and Dual IHC staining for CD 138 and Ki-67. H & E staining is done to evaluate various histological parameters like percentage of plasma cells, pattern of infiltration (nodular, interstitial, mixed and diffuse), routine parameters of marrow cellularity and hematopoiesis. Clinical data is collected from patient records from Medical Record Department. Each of CD138 expressing cells (cytoplasmic, red) are scored as proliferating plasma cells (containing a brown Ki¬67 nucleus) or non¬proliferating plasma cells (containing a blue, counter-stained, Ki-¬67 negative nucleus). Ki-67 is measured as percentage positivity with a maximum score of hundred percent and lowest of zero percent. The intensity of staining is not relevant. Results: Statistically significant correlation of Ki-67 in D-S Stage (Durie & Salmon Stage) I vs. III (p=0.026) and ISS (International Staging System) Stage I vs. III (p=0.019), β2m (p=0.029) and percentage of plasma cells (p < 0.001) is seen. No statistically significant correlation is seen between Ki-67 and hemoglobin, platelet count, total leukocyte count, total protein, albumin, S. calcium, S. creatinine, S. LDH, blood urea and pattern of infiltration. Conclusion: Ki-67 index correlated with other known prognostic parameters. However, it is not determined routinely in patients with MM due to little information available regarding its relevance and paucity of studies done to correlate with other known prognostic factors in MM patients. To the best of our knowledge, this is the first study in India using Dual IHC staining for Ki-67 and CD138 in MM patients. Routine determination of Ki-67 will help to identify patients who may benefit with more aggressive therapy. Recommendation: In this study follow up of patients is not included, and the sample size is small. Studying with larger sample size and long follow up is advocated to prognosticate Ki-67 as a marker of survival in patients with multiple myeloma.

Keywords: bone marrow, dual IHC, Ki-67, multiple myeloma

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Authors: Daisuke Sagiya, Ren Kamioka

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South Africa has ratified the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) on 30th November 2007. In line with this, the Department of Social Development (DSD) revised the White Paper on the Rights of Persons with Disabilities (WPRPD), and the Cabinet approved it on 9th December 2015. The South African government is striving towards the elimination of poverty and inequality in line with UNCRPD and WPRPD. However, there are minimal programmes and services that have been provided to persons with disabilities in the rural community. In order to address current discriminative practices, disunity and limited self-representation in rural community, DSD in cooperation with the Japan International Cooperation Agency (JICA) is implementing the 'Project for the Promotion of Empowerment of Persons with Disabilities and Disability Mainstreaming' from May 2016 to May 2020. The project is targeting rural community as the project sites, namely 1) Collins Chabane municipality, Vhembe district, Limpopo and 2) Maluti-a-Phofung municipality, Thabo Mofutsanyana district, Free State. The project aims at developing good practices on Community-Based Inclusive Development (CBID) at the project sites which will be documented as a guideline and applied in other provinces in South Africa and neighbouring countries (Lesotho, Swaziland, Botswana, Namibia, Zimbabwe, and Mozambique). In cooperation with provincial and district DSD and local government, the project is currently implementing various community activities, for example: Establishment of Self-Help Group (SHG) of persons with disabilities and Peer Counselling in the villages, and will conduct Disability Equality Training (DET) and accessibility workshop in order to enhance the CBID in the project sites. In order to universalise good practices on CBID, the authors will explain lessons learned from the project by utilising the theories of disability and development studies and community psychology such as social model of disability, twin-track approach, empowerment theory, sense of community, helper therapy principle, etc. And the authors conclude that in order to realise social participation of persons with disabilities in rural community, CBID is a strong tool and persons with disabilities must play central roles in all spheres of CBID activities.

Keywords: community-based inclusive development, disability mainstreaming, empowerment of persons with disabilities, self-help group

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Authors: Mehves Isiklar Ekici, Ceyda Tuna Kirsaclioglu, Zarife Kuloglu, Aydan Kansu

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Malnutrition is an important cause of morbidity and mortality as it accounts for 45% of child deaths under the age of 5 worldwide. Therefore, early recognition and effective treatment of failure to thrive and malnutrition are important. In this study, it was aimed to retrospectively evaluate the nutritional support treatment approaches (nutrition education and diet enrichment / use of enteral nutrition products) applied in children followed up with growth failure without underlying organic causes, and to compare the efficacy of nutritional support treatments. In this study, children aged 1 month to 18 years diagnosed with growth failure who were followed up for at least 12 months between January 2011 and February 2020, were included. Anthropometric measurements at baseline and during follow-up, type of nutritional support therapy and treatment compliance were evaluated based on the retrospective records. 119 children (median age:3.2, 69 girls) were included in the study. Nutrition education and dietary enrichment were provided to 28% of the patients (Group 1). In addition to dietary education and recommendations, enteral nutrition supplements was given in 78% of them (Group 2). Compliance to the treatment rates of the patients in Group 1 and Group 2 were not significantly different at both 6th and 12th month controls. At the end of the follow up children who comply with the treatment in Group 1 had significant increase in weight for age z scores (-1.74 vs 0.05, respectively, p=0.019) and body mass index z scores (-1.47 vs -0.53, respectively, p=0.034) compared with baseline measurements. Similar to Group 1, in Group 2 children with treatment compliance, had a significant increase in weight for age z scores (-2.24 vs. -0.54, respectively, p=0.00) and body mass index z scores (-2.27 vs. -1.06, respectively, p=0.00) compared with baseline measurements. The rate of patients with severe malnutrition decreased from 15% to 12%, for moderate malnutrition decreased from 54% to 33%. Moreover, it was observed that this decrease in the rate of patients with both severe and moderate malnutrition was more prominent in patients under 3 years of age. Although there was a significant increase in anthropometric measurements with treatment in both groups, there was no significant difference in between two groups terms of change in anthropometric measurements (p>0.05), therefore effectiveness. Failure to thrive and malnutrition in infancy and childhood cause health problems that can affect adult life. To conclude, nutritional education - dietary enrichment. recommendations and use of enteral nutrition supplements were both proven beneficial in this study. Researchers are willing to underline that the most important part of the treatment is to include the family to the process to ensure the treatment compliance.

Keywords: enteral nutrition supplements, failure to thrive, malnutrition, nutritional education

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Authors: Valentina Dolmova

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What consumers choose to buy and who voters select on election days are two questions that have captivated the interest of both academics and practitioners for many decades. The importance of understanding what influences the behavior of those groups and whether or not we can predict or control it fuels a steady stream of research in a range of fields. By looking only at the past 40 years, more than 70 thousand scientific papers have been published in each field – consumer behavior and political psychology, respectively. From marketing, economics, and the science of persuasion to political and cognitive psychology - we have all remained heavily engaged. The ever-evolving technology, inevitable socio-cultural shifts, global economic conditions, and much more play an important role in choice-equations regardless of context. On one hand, this makes the research efforts always relevant and needed. On the other, the relatively low number of cross-field collaborations, which seem to be picking up only in more in recent years, makes the existing findings isolated into framed bubbles. By performing systematic research across both areas of psychology and building a parallel between theories and factors of influence, however, we find that there is not only a definitive common ground between the behaviors of consumers and voters but that we are moving towards a global model of choice. This means that the lines between contexts are fading which has a direct implication on what we should focus on when predicting or navigating buyers and voters’ behavior. Internal and external factors in four main categories determine the choices we make as consumers and as voters. Together, personal, psychological, social, and cultural create a holistic framework through which all stimuli in relation to a particular product or a political party get filtered. The analogy “consumer-voter” solidifies further. Leading academics suggest that this fundamental parallel is the key to managing successfully political and consumer brands alike. However, we distinguish additional four key stimuli that relate to those factor categories (1/ opportunity costs; 2/the memory of the past; 3/recognisable figures/faces and 4/conflict) arguing that the level of expertise a person has determines the prevalence of factors or specific stimuli. Our efforts take into account global trends such as the establishment of “celebrity politics” and the image of “ethically concerned consumer brands” which bridge the gap between contexts to an even greater extent. Scientists and practitioners are pushed to accept the transformative nature of both fields in social psychology. Existing blind spots as well as the limited number of research conducted outside the American and European societies open up space for more collaborative efforts in this highly demanding and lucrative field. A mixed method of research tests three main hypotheses, the first two of which are focused on the level of irrelevance of context when comparing voting or consumer behavior – both from the factors and stimuli lenses, the third on determining whether or not the level of expertise in any field skews the weight of what prism we are more likely to choose when evaluating options.

Keywords: buyers’ behaviour, decision-making, voters’ behaviour, social psychology

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Authors: Alexandra Emmanuelle Membangbi, Jacky Njiki Bikoï, Esther Del-florence Moni Ndedi, Marie Joseph Nkodo Mindimi, Donatien Serge Mbaga, Elsa Nguiffo Makue, André Chris Mikangue Mbongue, Martha Mesembe, George Ikomey Mondinde, Eric Walter Perfura-yone, Sara Honorine Riwom Essama

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Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment failed to distinguish active TB (ATB) from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), another cytokine secreted by activated T cells, is also involved in immune response against Mycobacterium tuberculosis. The aim of the study was to assess the capacity of IFN-γ and IL2 to evaluate the therapeutic response of patients on anti-tuberculosis treatment. Material and Methods: We conducted a cross-sectional study in the Pneumonology Departments of the Jamot Hospital in Yaoundé between May and August 2021. After signed the informed consent, the sociodemographic data, as well as 5 mL of blood, were collected in the crook of the elbow of each participant. Sixty-one subjects were selected (n= 61) and divided into 4 groups as followed: group 1: resistant tuberculosis (n=13), group 2: active tuberculosis (n=19), group 3 cured tuberculosis (n=16), and group 4: presumed healthy persons (n=13). The cytokines of interest were determined using an indirect Enzyme-linked Immuno-Sorbent Assay (ELISA) according to the manufacturer's recommendations. P-values < 0.05 were interpreted as statistically significant. All statistical calculations were performed using SPSS version 22.0 Results: The results showed that men were more 14/61 infected (31,8%) with a high presence in active and resistant TB groups. The mean age was 41.3±13.1 years with a 95% CI = [38.2-44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6±160.6 pg/mL and 26.6±13.0 pg/mL in active tuberculosis patients, 251.1±30.9 pg/mL and 21.4±9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3±93.3 pg/mL and 17.9±9.4 pg/mL in cured patients, 15.1±8.4 pg/mL and 5.3±2.6 pg/mL in participants presumed healthy (p <0.0001). Significant differences in IFN-γ and IL-2 rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful to evaluate the therapeutic response of anti-tuberculosis patients, particularly in the both cytokines association case, that could improve the accuracy of routine examinations.

Keywords: antibiotic therapy, interferon gamma, interleukin 2, tuberculosis

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Authors: Duncan Wallace, M-Tahar Kechadi

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In recent years, Machine Learning (ML) approaches have been successfully applied to an analysis of patient symptom data in the context of disease diagnosis, at least where such data is well codified. However, much of the data present in Electronic Health Records (EHR) are unlikely to prove suitable for classic ML approaches. Furthermore, as scores of data are widely spread across both hospitals and individuals, a decentralized, computationally scalable methodology is a priority. The focus of this paper is to develop a method to predict outliers in an out-of-hours healthcare provision center (OOHC). In particular, our research is based upon the early identification of patients who have underlying conditions which will cause them to repeatedly require medical attention. OOHC act as an ad-hoc delivery of triage and treatment, where interactions occur without recourse to a full medical history of the patient in question. Medical histories, relating to patients contacting an OOHC, may reside in several distinct EHR systems in multiple hospitals or surgeries, which are unavailable to the OOHC in question. As such, although a local solution is optimal for this problem, it follows that the data under investigation is incomplete, heterogeneous, and comprised mostly of noisy textual notes compiled during routine OOHC activities. Through the use of Deep Learning methodologies, the aim of this paper is to provide the means to identify patient cases, upon initial contact, which are likely to relate to such outliers. To this end, we compare the performance of Long Short-Term Memory, Gated Recurrent Units, and combinations of both with Convolutional Neural Networks. A further aim of this paper is to elucidate the discovery of such outliers by examining the exact terms which provide a strong indication of positive and negative case entries. While free-text is the principal data extracted from EHRs for classification, EHRs also contain normalized features. Although the specific demographical features treated within our corpus are relatively limited in scope, we examine whether it is beneficial to include such features among the inputs to our neural network, or whether these features are more successfully exploited in conjunction with a different form of a classifier. In this section, we compare the performance of randomly generated regression trees and support vector machines and determine the extent to which our classification program can be improved upon by using either of these machine learning approaches in conjunction with the output of our Recurrent Neural Network application. The output of our neural network is also used to help determine the most significant lexemes present within the corpus for determining high-risk patients. By combining the confidence of our classification program in relation to lexemes within true positive and true negative cases, with an inverse document frequency of the lexemes related to these cases, we can determine what features act as the primary indicators of frequent-attender and non-frequent-attender cases, providing a human interpretable appreciation of how our program classifies cases.

Keywords: artificial neural networks, data-mining, machine learning, medical informatics

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Authors: Kenneth A. Rostowsky, Alexander S. Maher, Nahian F. Chowdhury, Andrei Irimia

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The clinical significance of cerebral microbleeds (CMBs) due to mild traumatic brain injury (mTBI) remains unclear. Here we use magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and connectomic analysis to investigate the statistical association between mTBI-related CMBs, post-TBI changes to the human connectome and neurological/cognitive deficits. This study was undertaken in agreement with US federal law (45 CFR 46) and was approved by the Institutional Review Board (IRB) of the University of Southern California (USC). Two groups, one consisting of 26 (13 females) mTBI victims and another comprising 26 (13 females) healthy control (HC) volunteers were recruited through IRB-approved procedures. The acute Glasgow Coma Scale (GCS) score was available for each mTBI victim (mean µ = 13.2; standard deviation σ = 0.4). Each HC volunteer was assigned a GCS of 15 to indicate the absence of head trauma at the time of enrollment in our study. Volunteers in the HC and mTBI groups were matched according to their sex and age (HC: µ = 67.2 years, σ = 5.62 years; mTBI: µ = 66.8 years, σ = 5.93 years). MRI [including T1- and T2-weighted volumes, gradient recalled echo (GRE)/susceptibility weighted imaging (SWI)] and gradient echo (GE) DWI volumes were acquired using the same MRI scanner type (Trio TIM, Siemens Corp.). Skull-stripping and eddy current correction were implemented. DWI volumes were processed in TrackVis (http://trackvis.org) and 3D Slicer (http://www.slicer.org). Tensors were fit to DWI data to perform DTI, and tractography streamlines were then reconstructed using deterministic tractography. A voxel classifier was used to identify image features as CMB candidates using Microbleed Anatomic Rating Scale (MARS) guidelines. For each peri-lesional DTI streamline bundle, the null hypothesis was formulated as the statement that there was no neurological or cognitive deficit associated with between-scan differences in the mean FA of DTI streamlines within each bundle. The statistical significance of each hypothesis test was calculated at the α = 0.05 level, subject to the family-wise error rate (FWER) correction for multiple comparisons. Results: In HC volunteers, the along-track analysis failed to identify statistically significant differences in the mean FA of DTI streamline bundles. In the mTBI group, significant differences in the mean FA of peri-lesional streamline bundles were found in 21 out of 26 volunteers. In those volunteers where significant differences had been found, these differences were associated with an average of ~47% of all identified CMBs (σ = 21%). In 12 out of the 21 volunteers exhibiting significant FA changes, cognitive functions (memory acquisition and retrieval, top-down control of attention, planning, judgment, cognitive aspects of decision-making) were found to have deteriorated over the six months following injury (r = -0.32, p < 0.001). Our preliminary results suggest that acute post-TBI CMBs may be associated with cognitive decline in some mTBI patients. Future research should attempt to identify mTBI patients at high risk for cognitive sequelae.

Keywords: traumatic brain injury, magnetic resonance imaging, diffusion tensor imaging, connectomics

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Authors: Marina Karaseva

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The beginning of our century became a new digital epoch in the educational situation. Last decade the newest stage of this process had been initialized by the touch-screen mobile devices with program applications for them. The touch possibilities for learning fundamentals of music are of especially importance for music majors. The phenomenon of touching, firstly, makes it realistic to play on the screen as on music instrument, secondly, helps students to learn music theory while listening in its sound elements by music ear. Nowadays we can detect several levels of such mobile applications: from the basic ones devoting to the elementary music training such as intervals and chords recognition, to the more advanced applications which deal with music perception of non-major and minor modes, ethnic timbres, and complicated rhythms. The main purpose of the proposed paper is to disclose the main tendencies in this process and to demonstrate the most innovative features of music theory applications on the base of iOS and Android systems as the most common used. Methodological recommendations how to use these digital material musicologically will be done for the professional music education of different levels. These recommendations are based on more than ten year ‘iTheory’ teaching experience of the author. In this paper, we try to logically classify all types of ‘iTheory’mobile applications into several groups, according to their methodological goals. General concepts given below will be demonstrated in concrete examples. The most numerous group of programs is formed with simulators for studying notes with audio-visual links. There are link-pair types as follows: sound — musical notation which may be used as flashcards for studying words and letters, sound — key, sound — string (basically, guitar’s). The second large group of programs is programs-tests containing a game component. As a rule, their basis is made with exercises on ear identification and reconstruction by voice: sounds and intervals on their sounding — harmonical and melodical, music modes, rhythmic patterns, chords, selected instrumental timbres. Some programs are aimed at an establishment of acoustical communications between concepts of the musical theory and their musical embodiments. There are also programs focused on progress of operative musical memory (with repeating of sounding phrases and their transposing in a new pitch), as well as on perfect pitch training In addition a number of programs improvisation skills have been developed. An absolute pitch-system of solmisation is a common base for mobile programs. However, it is possible to find also the programs focused on the relative pitch system of solfegе. In App Store and Google Play Market online store there are also many free programs-simulators of musical instruments — piano, guitars, celesta, violin, organ. These programs may be effective for individual and group exercises in ear training or composition classes. Great variety and good sound quality of these programs give now a unique opportunity to musicians to master their music abilities in a shorter time. That is why such teaching material may be a way to effective study of music theory.

Keywords: ear training, innovation in music education, music theory, mobile devices

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Authors: Zihan Geng, L. Quentin Dixon

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It has been proposed that early bilingual experience confers a number of advantages in the development of executive control mechanisms. Although the literature provides empirical evidence for bilingual benefits, some studies also reported null or mixed results. To make sense of these contradictory findings, the current review synthesize recent empirical studies investigating bilingual effects on children’s executive function and attention control. The publication time of the studies included in the review ranges from 2010 to 2017. The key searching terms are bilingual, bilingualism, children, executive control, executive function, and attention. The key terms were combined within each of the following databases: ERIC (EBSCO), Education Source, PsycINFO, and Social Science Citation Index. Studies involving both children and adults were also included but the analysis was based on the data generated only by the children group. The initial search yielded 137 distinct articles. Twenty-eight studies from 27 articles with a total of 3367 participants were finally included based on the selection criteria. The selective studies were then coded in terms of (a) the setting (i.e., the country where the data was collected), (b) the participants (i.e., age and languages), (c) sample size (i.e., the number of children in each group), (d) cognitive outcomes measured, (e) data collection instruments (i.e., cognitive tasks and tests), and (f) statistic analysis models (e.g., t-test, ANOVA). The results show that the majority of the studies were undertaken in western countries, mainly in the U.S., Canada, and the UK. A variety of languages such as Arabic, French, Dutch, Welsh, German, Spanish, Korean, and Cantonese were involved. In relation to cognitive outcomes, the studies examined children’s overall planning and problem-solving abilities, inhibition, cognitive complexity, working memory (WM), and sustained and selective attention. The results indicate that though bilingualism is associated with several cognitive benefits, the advantages seem to be weak, at least, for children. Additionally, the nature of the cognitive measures was found to greatly moderate the results. No significant differences are observed between bilinguals and monolinguals in overall planning and problem-solving ability, indicating that there is no bilingual benefit in the cooperation of executive function components at an early age. In terms of inhibition, the mixed results suggest that bilingual children, especially young children, may have better conceptual inhibition measured in conflict tasks, but not better response inhibition measured by delay tasks. Further, bilingual children showed better inhibitory control to bivalent displays, which resembles the process of maintaining two language systems. The null results were obtained for both cognitive complexity and WM, suggesting no bilingual advantage in these two cognitive components. Finally, findings on children’s attention system associate bilingualism with heightened attention control. Together, these findings support the hypothesis of cognitive benefits for bilingual children. Nevertheless, whether these advantages are observable appears to highly depend on the cognitive assessments. Therefore, future research should be more specific about the cognitive outcomes (e.g., the type of inhibition) and should report the validity of the cognitive measures consistently.

Keywords: attention, bilingual advantage, children, executive function

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Authors: Azieva A. M., Yastremsky E. V., Kirillova D. A., Patsaev T. D., Sharikov R. V., Kamyshinsky R. A., Lukanina K. I., Sharikova N. A., Grigoriev T. E., Vasiliev A. L.

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Adhesive properties of scaffolds, which predominantly depend on the chemical and structural features of their surface, play the most important role in tissue engineering. The basic requirements for such scaffolds are biocompatibility, biodegradation, high cell adhesion, which promotes cell proliferation and differentiation. In many cases, synthetic polymers scaffolds have proven advantageous because they are easy to shape, they are tough, and they have high tensile properties. The regeneration of nerve tissue still remains a big challenge for medicine, and neural stem cells provide promising therapeutic potential for cell replacement therapy. However, experiments with stem cells have their limitations, such as low level of cell viability and poor control of cell differentiation. Whereas the study of already differentiated neuronal cell culture obtained from newborn mouse brain is limited only to cell adhesion. The growth and implantation of neuronal culture requires proper scaffolds. Moreover, the polymer scaffolds implants with neuronal cells could demand specific morphology. To date, it has been proposed to use numerous synthetic polymers for these purposes, including polystyrene, polylactic acid (PLA), polyglycolic acid, and polylactide-glycolic acid. Tissue regeneration experiments demonstrated good biocompatibility of PLA scaffolds, despite the hydrophobic nature of the compound. Problem with poor wettability of the PLA scaffold surface could be overcome in several ways: the surface can be pre-treated by poly-D-lysine or polyethyleneimine peptides; roughness and hydrophilicity of PLA surface could be increased by plasma treatment, or PLA could be combined with natural fibers, such as collagen or chitosan. This work presents a study of adhesion of both induced pluripotent stem cells (iPSCs) and mouse primary neuronal cell culture on the polylactide scaffolds of various types: oriented and non-oriented fibrous nonwoven materials and sponges – with and without the effect of plasma treatment and composites with collagen and chitosan. To evaluate the effect of different types of PLA scaffolds on the neuronal differentiation of iPSCs, we assess the expression of NeuN in differentiated cells through immunostaining. iPSCs more effectively differentiate into neurons on PLA scaffolds with high adhesive properties for primary neuronal cells.

Keywords: PLA scaffold, neurons, neuronal differentiation, stem cells, polylactid

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Martyn Queen, Diane Crone, Andrew Parker, Saul Bloxham

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Rationale: There is a growing body of evidence that supports the use of physical activity during and after cancer treatment. However, activity levels for patients remain low. As more cancer patients are treated successfully, and treatment costs continue to escalate, physical activity may be a promising adjunct to a person-centred healthcare approach to recovery. Aim: The aim was to further understand how physical activity may enhance the recovery process for a group of mixed-site cancer patients. Objectives: The research investigated longitudinal changes in physical activity and perceived the quality of life between two and six month’s post-exercise interventions. It also investigated support systems that enabled patients to sustain these perceived changes. Method: The respondent cohort comprised 14 mixed-site cancer patients aged 43-70 (11 women, 3 men), who participated in a two-phase physical activity intervention that took place at a university in the South West of England. Phase 1 consisted of an eight-week structured physical activity programme; Phase 2 consisted of four months of non-supervised physical activity. Semi-structured interviews took place three times over six months with each participant. Grounded theory informed the data collection and analysis which, in turn, facilitated theoretical development. Findings: Our findings propose three theories on the impact of physical activity for recovering cancer patients: 1) Knowledge gained through a structured exercise programme can enable recovering cancer patients to independently sustain physical activity to four-month follow-up. 2) Sustaining physical activity for six months promotes positive changes in the quality of life indicators of chronic fatigue, self-efficacy, the ability to self-manage and energy levels. 3) Peer support from patients facilitates adherence to a structured exercise programme and support from a spouse, or life partner facilitates independently sustained physical activity to four-month follow-up. Conclusions: This study demonstrates that qualitative research can provide an evidence base that could be used to support future care plans for cancer patients. Findings also demonstrate that a physical activity intervention can be effective at helping cancer patients recover from the side effects of their treatment, and recommends that physical activity should become an adjunct therapy alongside traditional cancer treatments.

Keywords: physical activity, health, cancer recovery, quality of life, support systems, qualitative, grounded theory, person-centred healthcare

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Authors: Joni Asitashvili, Eka Chabashvili, Maya Virsaladze, Alexander Chokhonelidze

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Studying the soundscape is a major challenge in many countries of the civilized world today. The sound environment and music itself are part of the Earth's ecosystem. Therefore, researching its positive or negative impact is important for a clean and healthy environment. The acoustics of nature gave people many musical ideas, and people enriched musical features and performance skills with the ability to imitate the surrounding sound. For example, a population surrounded by mountains invented the technique of antiphonal singing, which mimics the effect of an echo. Canadian composer Raymond Murray Schafer viewed the world as a kind of musical instrument with ever-renewing tuning. He coined the term "Soundscape" as a name of a natural environmental sound, including the sound field of the Earth. It can be said that from which the “music of nature” is constructed. In the 21st century, a new field–Ecomusicology–has emerged in the field of musical art to study the sound ecosystem and various issues related to it. Ecomusicology considers the interconnections between music, culture, and nature–According to the Aaron Allen. Eco-music is a field of ecomusicology concerning with the depiction and realization of practical processes using modern composition techniques. Finding an artificial sound source (instrumental or electronic) for the piece that will blend into the soundscape of Sound Oases. Creating a composition, which sounds in harmony with the vibrations of human, nature, environment, and micro- macrocosm as a whole; Currently, we are exploring the ambient sound of the Georgian urban and suburban environment to discover “Sound Oases" and compose Eco-music works. We called “Sound Oases" an environment with a specific sound of the ecosystem to use in the musical piece as an instrument. The most interesting examples of Eco-music are the round dances, which were already created in the BC era. In round dances people would feel the united energy. This urge to get united revealed itself in our age too, manifesting itself in a variety of social media. The virtual world, however, is not enough for a healthy interaction; we created plan of “contemporary round dance” in sound oasis, found during expedition in Georgian caves, where people interacted with cave's soundscape and eco-music, they feel each other sharing energy and listen to earth sound. This project could be considered a contemporary round dance, a long improvisation, particular type of art therapy, where everyone can participate in an artistic process. We would like to present research result of our eco-music experimental performance.

Keywords: eco-music, environment, sound, oasis

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Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

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Transient ischaemic attacks (TIAs) are warning signs for future strokes. TIA patients are at increased risk of stroke and cardio-vascular events after a first episode. A majority of studies on TIA focused on the occurrence of these ancillary events after a TIA. Long-term mortality after TIA received only limited attention. We undertook this study to determine the long-term hazards of all-cause mortality following a first episode of a TIA using anonymised electronic health records (EHRs). We used a retrospective case-control study using electronic primary health care records from The Health Improvement Network (THIN) database. Patients born prior to or in year 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general medical practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Weibull-Cox survival model which included both scale and shape effects and a random frailty effect of GP practice. 20,633 cases and 58,634 controls were included. Cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to matched controls (HR = 3.04, 95% CI (2.91 - 3.18)). The HRs for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to matched controls. Aspirin provided long-term survival benefits to cases. Cases aged 39-60 years on aspirin had HR of 0.93 (0.84 - 1.00), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5 years, 10 years and 15 years, respectively, compared to cases in the same age group who were not on antiplatelets. Similar beneficial effects of aspirin were observed in other age groups. There were no significant survival benefits with other antiplatelet options. No survival benefits of antiplatelet drugs were observed in controls. Our study highlights the excess long-term risk of death of TIA patients and cautions that TIA should not be treated as a benign condition. The study further recommends aspirin as the better option for secondary prevention for TIA patients compared to clopidogrel recommended by NICE guidelines. Management of risk factors and treatment strategies should be important challenges to reduce the burden of disease.

Keywords: dual antiplatelet therapy (DAPT), General Practice, Multiple Imputation, The Health Improvement Network(THIN), hazard ratio (HR), Weibull-Cox model

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Authors: Robert Pocklington

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Most current language courses expect students to be ‘vocational’, sacrificing their free time in order to learn. However, pupils with a full-time job, or bringing up children, hardly have a spare moment. Others just need the language as a tool or a qualification, as if it were book-keeping or a driving license. Then there are children in unstructured families whose stressful life makes private study almost impossible. And the countless parents whose evenings and weekends have become a nightmare, trying to get the children to do their homework. There are many arguments against homework being a necessity (rather than an optional extra for more ambitious or dedicated students), making a clear case for teaching methods which facilitate full learning of the key content within the classroom. A methodology which could be described as Programmed Mastery Learning has been used at Fluency Language Academy (Spain) since 1992, to teach English to over 4000 pupils yearly, with a staff of around 100 teachers, barely requiring homework. The course is structured according to the tenets of Programmed Learning: small manageable teaching steps, immediate feedback, and constant successful activity. For the Mastery component (not stopping until everyone has learned), the memorisation and practice are entrusted to flashcard-based drilling in the classroom, leading all students to progress together and develop a permanently growing knowledge base. Vocabulary and expressions are memorised using flashcards as stimuli, obliging the brain to constantly recover words from the long-term memory and converting them into reflex knowledge, before they are deployed in sentence building. The use of grammar rules is practised with ‘cue’ flashcards: the brain refers consciously to the grammar rule each time it produces a phrase until it comes easily. This automation of lexicon and correct grammar use greatly facilitates all other language and conversational activities. The full B2 course consists of 48 units each of which takes a class an average of 17,5 hours to complete, allowing the vast majority of students to reach B2 level in 840 class hours, which is corroborated by an 85% pass-rate in the Cambridge University B2 exam (First Certificate). In the past, studying for qualifications was just one of many different options open to young people. Nowadays, youngsters need to stay at school and obtain qualifications in order to get any kind of job. There are many students in our classes who have little intrinsic interest in what they are studying; they just need the certificate. In these circumstances and with increasing government pressure to minimise failure, teachers can no longer think ‘If they don’t study, and fail, its their problem’. It is now becoming the teacher’s problem. Teachers are ever more in need of methods which make their pupils successful learners; this means assuring learning in the classroom. Furthermore, homework is arguably the main divider between successful middle-class schoolchildren and failing working-class children who drop out: if everything important is learned at school, the latter will have a much better chance, favouring inclusiveness in the language classroom.

Keywords: flashcard drilling, fluency method, mastery learning, programmed learning, teaching English as a foreign language

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Authors: Daifeng Hao, Guang Feng, Jingfeng Zhao, Tao Li, Xiaoye Tuo

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Objective: To retrospectively analyze the clinical characteristics of incision infection with sternal osteomyelitis sinus tract after cardiac surgery and the operation method and therapeutic effect of filling and repairing with activated PRP gel. Methods: From March 2011 to October 2022, 142 cases of incision infection after cardiac surgery with sternal osteomyelitis sinus were retrospectively analyzed, and the causes of poor wound healing after surgery, wound characteristics, perioperative wound management were summarized. Treatment during operation, collection and storage process of autologous PRP before debridement surgery, PRP filling repair and activation method after debridement surgery, effect of anticoagulant drugs on surgery, postoperative complications and average wound healing time, etc.. Results: Among the cases in this group, 53.3% underwent coronary artery bypass grafting, 36.8% underwent artificial heart valve replacement, 8.2% underwent aortic artificial vessel replacement, and 1.7% underwent allogeneic heart transplantation. The main causes of poor incision healing were suture reaction, fat liquefaction, osteoporosis, diabetes, and metal allergy in sequence. The wound is characterized by an infected sinus tract. Before the operation, 100-150ml of PRP with 4 times the physiological concentration was collected separately with a blood component separation device. After sinus debridement, PRP was perfused to fill the bony defect in the middle of the sternum, activated with thrombin freeze-dried powder and calcium gluconate injection to form a gel, and the outer skin and subcutaneous tissue were sutured freely. 62.9% of patients discontinued warfarin during the perioperative period, and 37.1% of patients maintained warfarin treatment. There was no significant difference in the incidence of postoperative wound hematoma. The average postoperative wound healing time was 12.9±4.7 days, and there was no obvious postoperative complication. Conclusions: Application of activated PRP gel to fill incision infection with sternal osteomyelitis sinus after cardiac surgery has a less surgical injury and satisfactory and stable curative effect. It can completely replace the previously used pectoralis major muscle flap transplantation operation scheme.

Keywords: platelet-rich plasma, negative-pressure wound therapy, sternal osteomyelitis, cardiac surgery

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Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

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Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: M. G. Talasbayen, N. N. Dyussenbayev, Y. D. Kali, R. A. Zholbarysov, Y. N. Duissenbayev, I. Z. Mammadinova, S. M. Nuradilov

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Background. Hemorrhagic stroke is an acute cerebrovascular accident resulting from rupture of a cerebral vessel or increased permeability of the wall and imbibition of blood into the brain parenchyma. Arterial hypertension is a common cause of hemorrhagic stroke. Male gender and age over 55 years is a risk factor for intracerebral hemorrhage. Treatment of intracerebral hemorrhage is aimed at the primary pathophysiological link: the relief of coagulopathy and the control of arterial hypertension. Early surgical treatment can limit cerebral compression; prevent toxic effects of blood to the brain parenchyma. Despite progress in the development of neuroimaging data, the use of minimally invasive techniques, and navigation system, mortality from intracerebral hemorrhage remains high. Materials and methods. The study included 78 patients (62.82% male and 37.18% female) with a verified diagnosis of hemorrhagic stroke in the period from 2019 to 2021. The age of patients ranged from 25 to 80 years, the average age was 54.66±11.9 years. Demographic, brain CT data (localization, volume of hematomas), methods of treatment, and disease outcome were analyzed. Results. The retrospective analyze demonstrate that 78.2% of all patients underwent surgical treatment: decompressive craniectomy in 37.7%, craniotomy with hematoma evacuation in 29.5%, and hematoma draining in 24.59% cases. The study of the proportion of deaths, depending on the volume of intracerebral hemorrhage, shows that the number of deaths was higher in the group with a hematoma volume of more than 60 ml. Evaluation of the relationship between the time before surgery and mortality demonstrates that the most favorable outcome is observed during surgical treatment in the interval from 3 to 24 hours. Mortality depending on age did not reveal a significant difference between age groups. An analysis of the impact of the surgery type on mortality reveals that decompressive craniectomy with or without hematoma evacuation led to an unfavorable outcome in 73.9% of cases, while craniotomy with hematoma evacuation and drainage led to mortality only in 28.82% cases. Conclusion. Even though the multimodal approaches, the development of surgical techniques and equipment, and the selection of optimal conservative therapy, the question of determining the tactics of managing and treating hemorrhagic strokes is still controversial. Nevertheless, our experience shows that surgical intervention within 24 hours from the moment of admission and craniotomy with hematoma evacuation improves the prognosis of treatment outcomes.

Keywords: hemorragic stroke, Intracerebral hemorrhage, surgical treatment, stroke mortality

Procedia PDF Downloads 79

Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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Authors: Nadine khadraoui, Rym Essid, Olfa Tabbene, Imen Chniba, Safa Boujemaa, Selim Jallouli, Nadia Fares, Behija Mlik, Boutheina Ben Abdelmoumen Mardassi

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Background and aim: Mycoplasma hominis is an opportunistic pathogen that can cause various gynecological infections such cervicitis, infertility, and, less frequently, extra-genital infections. Previous studies on the antimicrobial susceptibility of Mycoplasma hominis Tunisian strains have highlighted a significant resistance, even multi-resistance, to the most used antibiotic in the therapy of consequential infections. To address this concern, the present study aimed for the alternative of phytotherapy. Peganum harmala seed extract was tested as an antibacterial agent against multidrug-resistant M.hominis clinical strains. Material and Methods: Peganum harmala plant was collected from Ain Sebaa, Tabarka, North West region of Tunisia in April 2018, air-dried, grounded and extracted by different solvents.The crude methanolic extract was further partitioned with n-HEX, DCM, EtOAC and n-BuOl. Antibacterial activity was evaluated against M. hominis ATCC 23114 and 20 M. hominis clinical strains.The antimycoplasmal activity was tested by the microdilution method, and MIC values were determined. Phytochemical analysis and hemolytic activity on human erythrocytes were also performed. The active fraction was then subjected to purification, and the chemical identification of the active compound was investigated. Results: Among the tested fractions, the n-BuOH extract was the most active fraction since it exhibited an inhibitory effect against M. hominis ATCC 23114 and 80% of the tested clinical strains with MIC between 125 and 1000 µg/ml. The phytochemical analysis of the n-BuOH revealed its metabolic abundance in polyphenols, flavonoids and condensed tannin with levels of 257.37 mg AGE/g, 172.27 mg EC/g and 58.27 mg EC/g, respectively. In addition, P. harmala n-BuOH extract exhibited potent bactericidal activity against all M. hominis isolates with CMB values ranging between 125 and 4000 µg/ml. Further, the active fraction exhibited weak cytotoxicity effect at active concentrations when tested on human erythrocytes. The active compound was identified by gas chromatography–mass spectrometry as an indole alkaloid harmaline. Conclusion: In summary, Peganum harmala extract demonstrated an interesting anti-mycoplasmal activity against M. hominis Tunisian strains. Therefore, it could be considered as a potential candidate for the treatment of consequential infections. However, further studies are necessary to evaluate its mechanism of action in mycoplasmas.

Keywords: mycoplasma hominis, peganum harmala, antibioresistance, phytotherapy, phytochemical analysis

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: M. A. Okezue, K. L. Clase, S. R. Byrn

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The requirement for maintaining data integrity in laboratory operations is critical for regulatory compliance. Automation of procedures reduces incidence of human errors. Quality control laboratories located in low-income economies may face some barriers in attempts to automate their processes. Since data from quality control tests on pharmaceutical products are used in making regulatory decisions, it is important that laboratory reports are accurate and reliable. Zinc Sulphate (ZnSO₄) tablets is used in treatment of diarrhea in pediatric population, and as an adjunct therapy for COVID-19 regimen. Unfortunately, zinc content in these formulations is determined titrimetrically; a manual analytical procedure. The assay for ZnSO4 tablets involves time-consuming steps that contain mathematical formulae prone to calculation errors. To achieve consistency, save costs, and improve data integrity, validated spreadsheets were developed to simplify the two critical steps in the analysis of ZnSO4 tablets: standardization of 0.1M Sodium Edetate (EDTA) solution, and the complexometric titration assay procedure. The assay method in the United States Pharmacopoeia was used to create a process flow for ZnSO₄ tablets. For each step in the process, different formulae were input into two spreadsheets to automate calculations. Further checks were created within the automated system to ensure validity of replicate analysis in titrimetric procedures. Validations were conducted using five data sets of manually computed assay results. The acceptance criteria set for the protocol were met. Significant p-values (p < 0.05, α = 0.05, at 95% Confidence Interval) were obtained from students’ t-test evaluation of the mean values for manual-calculated and spreadsheet results at all levels of the analysis flow. Right-first-time analysis and principles of data integrity were enhanced by use of the validated spreadsheet calculators in titrimetric evaluations of ZnSO₄ tablets. Human errors were minimized in calculations when procedures were automated in quality control laboratories. The assay procedure for the formulation was achieved in a time-efficient manner with greater level of accuracy. This project is expected to promote cost savings for laboratory business models.

Keywords: data integrity, spreadsheets, titrimetry, validation, zinc sulphate tablets

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Authors: Hailemeleak Regassa

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Traditional medicines use medicinal plants as a source of ingredients, and many modern medications are indirectly derived from plants. Consumers in affluent nations are growing disenchanted with contemporary healthcare and looking for alternatives. Oxidative stress is the primary cause of multiple diseases, and exogenous antioxidant supplementation or strengthening the body's endogenous antioxidant defenses are potential ways to counteract the negative effects of oxidative damage. Plants can biosynthesize non-enzymatic antioxidants that can reduce ROS-induced oxidative damage. Aging often aids the propagation and development of carcinogenesis, and older animals and older people exhibit increased vulnerability to tumor promoters. Cancer is a major public health issue, with several anti-cancer medications in clinical use. Potential drugs such as flavopiridol, roscovitine, combretastatin A-4, betulinic acid, and silvestrol are in the clinical or preclinical stages of research. Methodology: Microbial Growth media, Dimethyl sulfoxide (DMSO), methanol, ethyl acetate, and n-hexane were obtained from Himedia Labs, Mumbai, India. plant were collected from the Herbal Garden of Shoolini University campus, Solan, India (Latitude - 30.8644° N and longitude - 77.1184° E). The identity was confirmed by Dr. Y.S. Parmar University of Horticulture and Forestry, Nauni, Solan (H.P.), India, and documented in Voucher specimens - UHF- Herbarium no. 13784; vide book no. 3818 Receipt No. 086. The plant materials were washed with tap water, and 0.1% mercury chloride for 2 minutes, rinsed with distilled water, air dried, and kept in a hot air oven at 40ºc on blotting paper until all the water evaporated and became well dried for grinding. After drying, the plant materials were grounded using a mixer grinder into fine powder transferred into airtight containers with proper labeling, and stored at 4ºc for future use (Horablaga et al., 2023). The extraction process was done according to Altemimi et al., 2017. The 5g powder was mixed with 15 ml of the respective solvents (n-hexane, ethyl acetate, and methanol), and kept for 4-5 days on the platform shaker. The solvents used are based on their increasing polarity index. Then the extract was centrifuged at 10,000rpm for 5 minutes and filtered using No.1 Whatman filter paper.

Keywords: cancer, phytomedicine, medicinal plants, oncology

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Authors: Vinod Kumar

Abstract:

Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

Procedia PDF Downloads 289

Authors: Laverne Seales

Abstract:

When most people think of Panama, they immediately think of the Canal; however, the construction and the people who made it possible are often omitted and seldom acknowledged. The reality is that the construction of this waterway was achieved through forced migration and discriminatory practices toward people of African descent, specifically black people from the Caribbean. From the colonial period to the opening and subsequent operation of the Panama Canal by the United States, this paper goes through the rich layers of Panamanian history to examine the life of Afro-Caribbeans and their descendants in Panama. It also considers the role of the United States in Panama; it explores how the United States in Panama forged a racially complex country that made the integration of Afro-Caribbeans and their descendants difficult. After laying a historical foundation, the exploration of Afro-Caribbean people and Panamanians of Afro-Caribbean descent are analyzed through Afro-Panamanian writer Carlos Guillermo ‘Cubena’ Wilson's novels, short stories, and poetry. This study focuses on how Cubena addresses racism, discrimination, inequality, and social justice issues towards Afro-Caribbeans and their descendants who traveled to Panama to construct the Canal. Content analysis methodology can yield several significant contributions, and analyzing Carlos Guillermo Wilson's literature under this framework allows us to consider social commentary and critique of Panamanian society. It identifies the social issues and concerns of Afro-Caribbeans and people of Afro-Caribbean descent, such as inequality, corruption, racism, political oppression, and cultural identity. Analysis methodology allows us to explore how Cubena's literature engages with questions of cultural identity and belonging in Panamanian society. By examining themes related to race, ethnicity, language, and heritage, this research uncovers the complexities of Panamanian cultural identity, allowing us to interrogate power dynamics and social hierarchies in Panamanian society. Analyzing the portrayal of different social groups, institutions, and power structures helps uncover how power is wielded, contested, and resisted; Cubena's fictional world allows us to see how it functions in Panama. Content analysis methodology also provides for critiquing political systems and governance in Panama. By examining the representation and presentation of political figures, institutions, and events in Cubena's literature, we uncover his commentary on corruption, authoritarianism, governance, and the role of the United States in Panama. Content analysis highlights how Wilson's literature amplifies the voices and experiences of marginalized individuals and communities in Panamanian society. By centering the narratives of Afro-Panamanians and other marginalized groups, this researcher uncovers Cubena's commitment to social justice and inclusion in his writing and helps the reader engage with historical narratives and collective memory in Panama. Overall, analyzing Carlos Guillermo ‘Cubena’ Wilson's literature as a platform for social commentary and critique of Panamanian society using content analysis methodology provides valuable insights into the cultural, social, and political dimensions of Afro-Panamanians during and after the construction of the Panama Canal.

Keywords: Afro-Caribbean, Panama Canal, race, Afro-Panamanian, identity, history

Procedia PDF Downloads 12

Authors: Madeleine Elder, Aye Htun

Abstract:

Background: Myiasis is the parasitic infestation of body tissues by fly larvae. It predominantly occurs in poor socioeconomic regions of tropical and subtropical countries where it is associated with poor hygiene and sanitation. Cutaneous and wound myiasis are the most common presentations whereas urogenital myiasis is rare, with few reported cases. Case: a 26-year-old primiparous woman with a low-risk pregnancy presented to the emergency department at 37+3-weeks’ gestation after passing a 2cm black larva during micturition, with 2 weeks of mild vulvar pruritus and dysuria. She had travelled to India 9-months prior. Examination of the external genitalia showed small white larvae over the vulva and anus and a mildly inflamed introitus. Speculum examination showed infiltration into the vagina and heavy white discharge. High vaginal swab reported Candida albicans. Urine microscopy reported bacteriuria with Enterobacter cloacae. Urine parasite examination showed myiasis caused by Clogmia albipunctata species of fly larvae from the family Psychodidae. Renal tract ultrasound and inflammatory markers were normal. Infectious diseases, urology and paediatric teams were consulted. The woman received treatment for her urinary tract infection (which was likely precipitated by bladder irritation from local parasite infestation) and vaginal candidiasis. She underwent daily physical removal of parasites with cleaning, speculum examination and removal, and hydration to promote bladder emptying. Due to the risk of neonatal exposure, aspiration pneumonitis and facial infestation, the woman was steroid covered and proceeded to have an elective caesarean section at 38+3-weeks’ gestation, with delivery of a healthy infant. She then proceeded to have a rigid cystoscopy and washout, which was unremarkable. Placenta histopathology revealed focal eosinophilia in keeping with the history of maternal parasites. Conclusion: Urogenital myiasis is very rare, especially in the developed world where it is seen in returned travellers. Treatment may include systemic therapy with ivermectin and physical removal of parasites. During pregnancy, physical removal is considered the safest treatment option, and discussion around the timing and mode of delivery should consider the risk of harm to the foetus.

Keywords: urogenital myiasis, parasitic infection, infection in pregnancy, returned traveller

Procedia PDF Downloads 99

Authors: Colleen Cleveland, W. Adam Baldowski

Abstract:

In the dynamic realm of online education, the integration of games and entertainment has emerged as a powerful strategy to captivate learners, drive active participation, and cultivate meaningful learning experiences. This abstract presents an overview of the upcoming conference, "Game On," dedicated to exploring the transformative impact of gamification, interactive simulations, and multimedia content in the digital learning landscape. Introduction: The conference aims to blur the traditional boundaries between education and entertainment, inspiring learners of diverse ages and backgrounds to actively engage in their online learning journeys. By leveraging the captivating elements of games and entertainment, educators can enhance motivation, retention, and deep understanding among virtual classroom participants. Conference Highlights: Commencing with an exploration of theoretical foundations drawing from educational psychology, instructional design, and the latest pedagogical research, participants will gain valuable insights into the ways gamified elements elevate the quality of online education. Attendees can expect interactive sessions, workshops, and case studies showcasing best practices and innovative strategies, including game-based assessments and virtual reality simulations. Inclusivity and Diversity: The conference places a strong emphasis on inclusivity, accessibility, and diversity in the integration of games and entertainment for educational purposes. Discussions will revolve around accommodating diverse learning styles, overcoming potential challenges, and ensuring equitable access to engaging educational content for all learners. Educational Transformation: Educators, instructional designers, and e-learning professionals attending "Game On" will acquire practical techniques to elevate the quality of their online courses. The conference promises a stimulating and informative exploration of blending education with entertainment, unlocking the untapped potential of games and entertainment in online education. Conclusion: "Game On" invites participants to embark on a journey that transforms online education by harnessing the power of entertainment. This event promises to be a cornerstone in the evolution of virtual learning, offering valuable insights for those seeking to create a more engaging and effective online educational experience. Join us as we explore new horizons, pushing the boundaries of online education through the fusion of games and entertainment.

Keywords: online education, games, entertainment, psychology, therapy, pop culture

Procedia PDF Downloads 27

Authors: Bruno R. Mendes, Francisco J. Caldeira, Rita S. Luís

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Population ageing is directly correlated to an increase in medicine consumption. Beyond the latter and the polymedicated profile of elderly, it is possible to see a need for pharmacotherapeutic monitoring due to cognitive and physical impairment. In this sense, the tracking, organization and administration of medicines become a daily challenge and the pill-box dispenser system a solution. The pill-box dispenser (system) consists in a small compartmentalized container to unit dose organization, which means a container able to correlate the patient’s prescribed dose regimen and the time schedule of intake. In many European countries, this system is part of pharmacist’s role in clinical pharmacy. Despite this simple solution, therapy compliance is only possible if the patient adheres to the system, so it is important to establish a qualitative and quantitative analysis on the perception of the patient on the benefits and risks of the pill-box dispenser as well as the identification of the ideal system. The analysis was conducted through an observational study, based on the application of a standardized questionnaire structured with the numerical scale of Likert (5 levels) and previously validated on the population. The study was performed during a limited period of time and under a randomized sample of 188 participants. The questionnaire consisted of 22 questions: 6 background measures and 16 specific measures. The standards for the final comparative analysis were obtained through the state-of-the-art on the subject. The study carried out using the Likert scale afforded a degree of agreement and discordance between measures (Sample vs. Standard) of 56,25% and 43,75%, respectively. It was concluded that the pill-box dispenser has greater acceptance among a younger population, that was not the initial target of the system. However, this allows us to guarantee a high adherence in the future. Additionally, it was noted that the cost associated with this service is not a limiting factor for its use. The pill-box dispenser system, as currently implemented, demonstrates an important weakness regarding the quality and effectiveness of the medicines, which is not understood by the patient, revealing a significant lack of literacy when it concerns with medicine area. The characteristics of an ideal system remain unchanged, which means that the size, appearance and availability of information in the pill-box continue to be indispensable elements for the compliance with the system. The pill-box dispenser remains unsuitable regarding container size and the type of treatment to which it applies. Despite that, it might be a future standard for clinical pharmacy, allowing a differentiation of the pharmacist role, as well as a wider range of applications to other age groups and treatments.

Keywords: clinical pharmacy, medicines, patient safety, pill-box dispenser

Procedia PDF Downloads 173