Search results for: child-centered play therapy

Authors: Dileep Kumar Verma, Sunil Kumar Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: M. Naude, R. Joubert, A. du Plessis, S. Pelser, M. Trollip

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Context: The study focuses on the perceptions of South African parents and teachers regarding a play-based financial literacy program for children aged 3 to 6 years at an early childhood facility. It emphasizes the importance of early interventions in financial education to reduce poverty and inequality. Research Aim: To explore how parental involvement in teaching money management concepts to young children can support financial literacy education both at school and at home. Methodology: A qualitative deductive case study was conducted at a South African early childhood facility involving 90 children, their teachers and their families. Thematic content analysis of online survey responses and focus group discussions with teachers were used to identify patterns and themes related to participants’ perceptions of the financial literacy program. Validity: The study's validity and reproducibility are ensured by the depth and honesty of the data, participant involvement, and the inquirer's objectivity. Reliability aligns with the interpretive paradigm of this study, while transparency in data gathering and analysis enhances its trustworthiness. Credibility is further supported by using two triangulation methods: focus group interviews with teachers and open-ended questionnaires from parents. Findings: Parents reported overall satisfaction with the program and highlighted the development of essential money management skills in their children. They emphasized the collaborative role of home and school environments in fostering financial literacy in early childhood. Teachers reported that communication and interaction with the parents increased and grew. Healthy and positive relationships were established between the teachers and the parents which contributed to the success of the classroom financial literacy program. Theoretical Importance: The study underscores the significance of play-based financial literacy education in early childhood and the critical role of parental involvement in reinforcing money management concepts. It contributes to laying a solid foundation for children's future financial well-being. Data Collection: Data was collected through an online survey administered to parents of children participating in the financial literacy program over a period of 10 weeks. Focus group discussions were utilized with the teachers of each class after the conclusion of the program. Analysis Procedures: Thematic content analysis was applied to the survey responses to identify patterns, themes, and insights related to the participants’ perceptions of the program's effectiveness in teaching money management concepts to young children. Question Addressed: How does parental involvement in teaching money management concepts to young children support financial literacy education in early childhood? Conclusion: The study highlights the positive impact of a play-based financial literacy program for children aged 3 to 6 years and underscores the importance of collaboration between home and school environments in fostering financial literacy skills.

Keywords: early childhood, financial literacy, money management, parent involvement, play-based learning, South Africa

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Authors: Ewelina Musielak, Agnieszka Feliczak-Guzik, Izabela Nowak

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Based on the latest data, it is expected that the substances of therapeutic interest used will be as natural as possible. Therefore, active substances with the highest possible efficacy and low toxicity are sought. Among natural substances with therapeutic effects, those of plant origin stand out. Curcumin isolated from the Curcuma longa plant has proven to be particularly important from a medical point of view. Due to its ability to regulate many important transcription factors, cytokines, and protein kinases, curcumin has found use as an anti-inflammatory, antioxidant, antiproliferative, antiangiogenic, and anticancer agent. The unfavorable properties of curcumin, such as low solubility, poor bioavailability, and rapid degradation under neutral or alkaline pH conditions, limit its clinical application. These problems can be solved by combining curcumin with suitable carriers such as hierarchical zeolites. This is a new class of materials that exhibit several advantages. Hierarchical zeolites used as drug carriers enable delayed release of the active ingredient and promote drug transport to the desired tissues and organs. In addition, hierarchical zeolites play an important role in regulating micronutrient levels in the body and have been used successfully in cancer diagnosis and therapy. To apply curcumin to hierarchical zeolites synthesized from commercial FAU zeolite, solutions containing curcumin, carrier and acetone were prepared. The prepared mixtures were then stirred on a magnetic stirrer for 24 h at room temperature. The curcumin-filled hierarchical zeolites were drained into a glass funnel, where they were washed three times with acetone and distilled water, after which the obtained material was air-dried until completely dry. In addition, the effect of piperine addition to zeolite carrier containing a sufficient amount of curcumin was studied. The resulting products were weighed and the percentage of pure curcumin in the hierarchical zeolite was calculated. All the synthesized materials were characterized by several techniques: elemental analysis, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, Fourier transform infrared (FT-IR), N2 adsorption, and X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The aim of the presented study was to improve the biological activity of curcumin by applying it to hierarchical zeolites based on FAU zeolite. The results showed that the loading efficiency of curcumin into hierarchical zeolites based on commercial FAU-type zeolite is enhanced by modifying the zeolite carrier itself. The hierarchical zeolites proved to be very good and efficient carriers of plant-derived active ingredients such as curcumin.

Keywords: carriers of active substances, curcumin, hierarchical zeolites, incorporation

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Authors: Alaaeddeen M. Seufi

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Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.

Keywords: AMPs, insect, innate immunitty, therappeutics

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Authors: Lina Paola Orozco Marin, Yuliet Montoya Osorio, John Bustamante Osorno

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Ischemic events can culminate in acute myocardial infarction by irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Cell therapy seeks to replace these injured or necrotic cells by transplanting healthy and functional cells. The therapeutic alternatives proposed by tissue engineering and cardiovascular regenerative medicine are the use of biomaterials to mimic the native extracellular medium, which is full of proteins, proteoglycans, and glycoproteins. The selected biomaterials must provide structural support to the encapsulated cells to avoid their migration and death in the host tissue. In this context, the present research work focused on developing a natural thermosensitive hydrogel, its physical and chemical characterization, and the determination of its biocompatibility in vitro. The hydrogel was developed by mixing hydrolyzed bovine and porcine collagen at 2% w/v, chitosan at 2.5% w/v, and beta-glycerolphosphate at 8.5% w/w and 10.5% w/w in magnetic stirring at 4°C. Once obtained, the thermosensitivity and gelation time were determined, incubating the samples at 37°C and evaluating them through the inverted tube method. The morphological characterization of the hydrogels was carried out through scanning electron microscopy. Chemical characterization was carried out employing infrared spectroscopy. The biocompatibility was determined using the MTT cytotoxicity test according to the ISO 10993-5 standard for the hydrogel’s precursors using the fetal human ventricular cardiomyocytes cell line RL-14. The RL-14 cells were also seeded on the top of the hydrogels, and the supernatants were subculture at different periods to their observation under a bright field microscope. Four types of thermosensitive hydrogels were obtained, which differ in their composition and concentration, called A1 (chitosan/bovine collagen/beta-glycerolphosphate 8.5%w/w), A2 (chitosan/porcine collagen/beta-glycerolphosphate 8.5%), B1 (chitosan/bovine collagen/beta-glycerolphosphate 10.5%) and B2 (chitosan/porcine collagen/beta-glycerolphosphate 10.5%). A1 and A2 had a gelation time of 40 minutes, and B1 and B2 had a gelation time of 30 minutes at 37°C. Electron micrographs revealed a three-dimensional internal structure with interconnected pores for the four types of hydrogels. This facilitates the exchange of nutrients, oxygen, and the exit of metabolites, allowing to preserve a microenvironment suitable for cell proliferation. In the infrared spectra, it was possible to observe the interaction that occurs between the amides of polymeric compounds with the phosphate groups of beta-glycerolphosphate. Finally, the biocompatibility tests indicated that cells in contact with the hydrogel or with each of its precursors are not affected in their proliferation capacity for a period of 16 days. These results show the potential of the hydrogel to increase the cell survival rate in the cardiac cell therapies under investigation. Moreover, the results lay the foundations for its characterization and biological evaluation in both in vitro and in vivo models.

Keywords: cardiac cell therapy, cardiac ischemia, natural polymers, thermosensitive hydrogel

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Authors: Maha Salah Abdullah Ismail, Manal S. Ismail, Amir M. Saleh

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Reflexology treatment is a method for enhancing body relaxation. It is a widely recognized as an alternative therapy, effective for many health conditions. This study aimed to evaluate the effect of reflexology treatment on arterial blood gases among mechanically ventilated patients. A quasi-experimental (pre and post-test) research design was used. Research hypothesis was mechanically ventilated patients who will receive the reflexology treatment will have improvement in their arterial blood gases than those who will not. The current study was carried out in different Intensive Care Units at the Cairo University Hospitals. A purposeful sample of 100 adults’ mechanically ventilated patients was recruited over a period of three months of data collection. The participants were divided into two equally matched groups; (1) The study group who has received the routine care, in addition, two reflexology sessions on the feet, (2) The control group who has received only the routine care. One tool was utilized to collect data pertinent to the study; mechanically ventilated patients' data sheet that consists of demographic and medical data. Result: Majority (58% of the study group and 82% of the control group) were males, with mean age of 50.9 years in both groups. Patients who received the reflexology treatment significantly increase in the oxygen saturation pre second session (t=5.15, p=.000), immediate post sessions (t=4.4, p=.000) and post two hours (t= 4.7, p= .000). The study group was more likely to have lower PaO2 (F=5.025, p=.015), PaCo2 (F=4.952, p=.025) and higher HCo3 (F=15.211, p=.000) than the control group. Conclusion: This study results support the positive effect of reflexology treatment in improving some arterial blood gases among mechanically ventilated patients’ with the conventional therapy as in the study group there was increase in the oxygen saturation. In differences between groups there decrease PaO2, PaCo2 and increase HCo3 in the study group. Recommendation: Nurses should be trained how to demonstrate the foot reflexology among mechanically ventilated patients.

Keywords: arterial blood gases, foot, mechanical ventilated patient, reflexology

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Authors: Stephanie P. Nigro

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The Exhale Breath Hold (EBH) technique presents a promising approach to enhance the precision and efficacy of External Beam Radiation Therapy (EBRT) for abdominal tumours, which include liver, pancreas, kidney, and adrenal glands. These tumours are challenging to treat due to their proximity to organs at risk (OARs) and the significant motion induced by respiration and physiological variations, such as stomach filling. Respiratory motion can cause up to 40mm of displacement in abdominal organs, complicating accurate targeting. While current practices like limiting fasting help reduce motion related to digestive processes, they do not address respiratory motion. 4DCT scans are used to assess this motion, but they require extensive workflow time and expose patients to higher doses of radiation. The EBH technique, which involves holding the breath in an exhale with no air in the lungs, stabilizes internal organ motion, thereby reducing respiratory-induced motion. The primary benefit of EBH is the reduction in treatment volume sizes, specifically the Internal Target Volume (ITV) and Planning Target Volume (PTV), as demonstrated by smaller ITVs when gated in EBH. This reduction also improves the quality of 3D Cone Beam CT (CBCT) images by minimizing respiratory artifacts, facilitating soft tissue matching akin to stereotactic treatments. Patients suitable for EBH must meet criteria including the ability to hold their breath for at least 15 seconds and maintain a consistent breathing pattern. For those who do not qualify, the traditional 4DCT protocol will be used. The implementation involves an EBH planning scan and additional short EBH scans to ensure reproducibility and assist in contouring and volume expansions, with a Free Breathing (FB) scan used for setup purposes. Treatment planning on EBH scans leads to smaller PTVs, though intrafractional and interfractional breath hold variations must be accounted for in margins. The treatment decision process includes performing CBCT in EBH intervals, with careful matching and adjustment based on soft tissue and fiducial markers. Initial studies at two sites will evaluate the necessity of multiple CBCTs, assessing shifts and the benefits of initial versus mid-treatment CBCT. Considerations for successful implementation include thorough patient coaching, staff training, and verification of breath holds, despite potential disadvantages such as longer treatment times and patient exhaustion. Overall, the EBH technique offers significant improvements in the accuracy and quality of abdominal EBRT, paving the way for more effective and safer treatments for patients.

Keywords: abdominal cancers, exhale breath hold, radiation therapy, respiratory motion

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Authors: Shifu Hu, Qiong Yu, Wei Xia, Changhong Zhu

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Background: P38α MAPK, which is a member of the canonical MAPK family, is activated in response to various extracellular stresses and plays a role in multiple cellular processes. It is well known that p38α MAPK play vital roles in oocyte maturation, but the localization and functional roles of p38α MAPK during the meiotic maturation of rat oocytes remain unknown. Study Design: In this study, western-blot and immunofluorescent staining were used to investigate the expression and subcellular localization of p38α MAPK during the meiotic maturation of rat oocytes. SB203580, a specific inhibitor of p38α MAPK, was used to study the roles of p38α MAPK in the meiotic cell cycle of rat oocytes. Results: The results found that p38α MAPK phosphorylation (p-p38α MAPK, indicative of p38α MAPK activation) was low at the germinal vesicle (GV) stage, increased 3 h after germinal vesicle breakdown (GVBD), and maintained its maximum at MI (metaphase I) or M II (metaphase II). The p-p38α MAPK mainly accumulated in the germinal vesicle and had no obvious expression in the nucleus. From GVBD to M II, p-p38α MAPK was distributed in the cytoplasm around either the chromosomes or the spindle. We used SB203580, an inhibitor of p38α MAPK, to investigate the possible functional role of p38α MAPK during rat oocyte meiotic maturation. Treatment of GV stage oocytes with 20 μM SB203580 blocked p-p38α MAPK activity, and the spindles appeared abnormal. Additionally, the rate of GVBD after 3h of culture with 20 μM SB203580 (58.8%) was significantly inhibited compared with the control (82.5%, p < 0.05), and the polar body extrusion rate after 12 h of culture with SB203580 was also significantly decreased compared with the control (40.1 vs. 73.3%, p < 0.05). Conclusions: These data indicate that p38α MAPK may play a vital role in rat oocyte meiotic maturation.

Keywords: meiotic maturation, oocyte, p38α MAPK, spindle

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Authors: Shih-Chieh Liao, Jen-Ying Ma

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Dual protagonists game always bring a unique experience compared to the other games. This research wants to discuss whether the dual protagonists have the moving ability and special ability or not; it will affect the preference of the players. This research will focus on the single-player dual protagonists game. After the observation, we found that when players control the dual protagonists, the moving ability and special ability are a great point defining the preference of players. When players control the character, which is lack of moving ability, they often feel impatient with the inconvenient mechanism and then reduce the will to play with the character or even the game. Furthermore, the special ability is also important in the situation that there is another character to compare with. When the character is too powerful, players tend not to use the weaker one. In addition, gender is a big deal in the games. It surprisingly controls the will of play occasionally. In view of these, this research makes a single-player dual protagonists game and the dual protagonists are limited to male and female. The experiment content detected with Electrodermal Activity (EDA) includes seven different situations. (1) male and females both have the moving ability and special ability. (2) male and female both have a special ability, but female does not have the moving ability. (3) male and females both have a special ability, but the male does not have the moving ability. (4) male and female both have the moving ability, but the male does not have special ability (5) male and female both have the moving ability, but female does not have a special ability (6) male-only has the moving ability and female-only has a special ability (7) male-only has a special ability and female only has the moving ability. The experiment will evaluate the emotional changes of the subjects in those situations. The result sorted by the significance of player preference is (6)>(4)>(1)>(2)>(5)>(3)>(7). The result demonstrates that players prefer females with special abilities or males with moving abilities. The game developer could design the ability of dual protagonists based on this research. Therefore, players may have a better experience.

Keywords: biofeedback, dual protagonists, emotional responses, psychology, user experience

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Authors: Sophia Cyril Vincent

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Background: As per the Indian Census 2011, there is nearly 104 million elderly population aged above 60 years (53 million females and 51 males), and the count is expected to be 173 million by the end of 2026. Nearly 5.5% of women and 1.5% of men are living alone.1 In India, even though it is the moral duty of the children to take care of aged parents, many elders are landing in old age homes due to the social transformation factors like mushrooming of nuclear families, migration of children, cultural echoes, differences in mindset and values. Nearly 728 old age homes are seen across the country, out of which 78 old age homes with approximately 3000 inmates are seen only in Bangalore2. The existing literature shows that elderly women residing in old age homes experience the challenges like- loneliness, health issues, rejection from children, grief, death anxiety, etc, which leads to mental and physical wellbeing in numerous and tangible ways3. Hence the best and cost-effective way to improve the meaning and quality of life among elderly females is logotherapy, a type of psychotherapeutic analysis and treatment, motivating and driving force4 within the human experience to lead a decent life. Aim: The current research is aimed at studying the effectiveness of a logotherapy intervention on meaning and quality of life among elderly women of old age homes. Samples:200 women aged < 60 years and staying in the old age home for more than 1 year were randomly allocated to the control group and experimental group. Methodology: Using the Meaning in life questionnaire (MLQ)and the World health organization quality of life (WHOQOL) questionnaire, meaning and quality of life were assessed among both groups' women. Intensive Logotherapy and meaning in life program for five days were provided for the experimental group and the control group, with no treatment. Result: Under analysis. Conclusion: It is the right of the elderly woman to lead a happy and peaceful life till her death irrespective of the residing place. Hence, continuous monitoring and effective management are necessary for elderly women.

Keywords: quality of life, meaning of life, logo therapy, old age home

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Authors: Fares A. Mayia, Mahmoud A. Yamany, Mushabbab A. Asiri

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In recent years, non-invasive Focused Ultrasound (FU) has been utilized for generating bubbles (cavities) to ablate target tissue by mechanical fractionation. Intensities >10 kW/cm² are required to generate the inertial cavities. The generation, rapid growth, and collapse of these inertial cavities cause tissue fractionation and the process is called Histotripsy. The ability to fractionate tissue from outside the body has many clinical applications including the destruction of the tumor mass. The process of tissue fractionation leaves a void at the treated site, where all the affected tissue is liquefied to particles at sub-micron size. The liquefied tissue will eventually be absorbed by the body. Histotripsy is a promising non-invasive treatment modality. This paper presents a technique for generating inertial cavities at lower intensities (< 1 kW/cm²). The technique (patent pending) is based on amplitude modulation (AM), whereby a low frequency signal modulates the amplitude of a higher frequency FU wave. Cavitation threshold is lower at low frequencies; the intensity required to generate cavitation in water at 10 kHz is two orders of magnitude lower than the intensity at 1 MHz. The Amplitude Modulation technique can operate in both continuous wave (CW) and pulse wave (PW) modes, and the percentage modulation (modulation index) can be varied from 0 % (thermal effect) to 100 % (cavitation effect), thus allowing a range of ablating effects from Hyperthermia to Histotripsy. Furthermore, changing the frequency of the modulating signal allows controlling the size of the generated cavities. Results from in vitro work demonstrate the efficacy of the new technique in fractionating soft tissue and solid calcium carbonate (Chalk) material. The technique, when combined with MR or Ultrasound imaging, will present a precise treatment modality for ablating diseased tissue without affecting the surrounding healthy tissue.

Keywords: focused ultrasound therapy, histotripsy, inertial cavitation, mechanical tissue ablation

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Authors: Maliheh Rezaei

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Peace education has been introduced into many higher educational contexts by designing different programs, expecting to result in constructive changes, specifically in post-conflict countries. Teachers are the potential agents of positive change who play a major role in fostering the culture of peace in their classes. The purpose of this literature review was thus to evaluate the implementation of peace pedagogies by teachers in the context of higher education. More specifically, it addressed a) the role and characteristics of teachers and b) the pedagogies that they used to construct the culture of peace. The systematic literature review was used and several inclusion criteria were applied. Only papers published in English, which contained the keywords of university, higher education, peace, peace education, and similar derivatives such as ‘peacebuilding’ in their title and/or abstract, were included in this review. Moreover, only papers that dealt with the actual implementation of peace education theories were investigated. Findings highlighted that most teachers relied on pedagogies adopted from social justice, global citizenship, and positive psychology practices aiming to foster positive human traits such as resilience, empathy and reflection that were also believed to play an important role in peacebuilding efforts. Nevertheless, the incorporation of peace remained peripheral. The main challenge to incorporate the tenets of peace education was the shortage of teachers who were skilled and qualified enough to incorporate and promote the culture of peace in their classes. This literature review presents the body of research that has linked peace education to Higher Education. Therefore, it informs teachers about the potential roles they have in creating a peaceful and sustainable future. It also presents them with more effective pedagogies and practices to successfully integrate peace-related activities in Higher Education.

Keywords: culture of peace, higher education, teacher, pedogogy

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Authors: Shawna Staud, Mary Kaye Scaramucci

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Objective: Rubber cup polishing has been a traditional method of preventative therapy in dental hygiene treatment. Newer methods such as air polishing have changed the way dental hygiene care is provided, yet this technique has not been embraced by students in the program nor by practitioners in the workforce. Students entering the workforce tend to follow office protocol and are limited in confidence to introduce technologies learned in the curriculum. This project was designed to help students gain confidence in newer skills and encourage private practice settings to adopt newer technologies for patient care. Our program recently introduced air polishing earlier in the program before the rubber cup technique to determine if students would embrace the technology to become leading-edge professionals when they enter the marketplace. Methods: The class of 2022 was taught the traditional method of polishing in the first-year curriculum and air polishing in the second-year curriculum. The class of 2023 will be taught the air polishing method in the first-year curriculum and the traditional method of polishing in the second-year curriculum. Pre- and post-graduation survey data will be collected from both cohorts. Descriptive statistics and pre and post-paired t-tests with alpha set at .05 to compare pre and post-survey results will be used to assess data. Results: This study is currently in progress, with a completion date of October 2023. The class of 2022 completed the pre-graduation survey in the spring of 2022. The post-gradation survey will be sent out in October 2022. The class of 2023 cohort will be surveyed in the spring of 2023 and October 2023. Conclusion: Our hypothesis is students who are taught air polishing first will be more inclined to adopt that skill in private practice, thereby embracing newer technology and improving oral health care.

Keywords: luggage handling system at world’s largest pilgrimage center

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Authors: Raghava Dhanya, Shashank S.

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This paper delves into the intersection of chess and computer science, specifically focusing on the efficient representation of chess game states. We propose two methods: the Static Method and the Dynamic Method, each offering unique advantages in terms of space efficiency and computational complexity. The Static Method aims to represent the game state using a fixedlength encoding, allocating 192 bits to capture the positions of all pieces on the board. This method introduces a protocol for ordering and encoding piece positions, ensuring efficient storage and retrieval. However, it faces challenges in representing pieces no longer in play. In contrast, the Dynamic Method adapts to the evolving game state by dynamically adjusting the encoding length based on the number of pieces in play. By incorporating Alive Bits for each piece kind, this method achieves greater flexibility and space efficiency. Additionally, it includes provisions for encoding additional game state information such as castling rights and en passant squares. Our findings demonstrate that the Dynamic Method offers superior space efficiency compared to traditional Forsyth-Edwards Notation (FEN), particularly as the game progresses and pieces are captured. However, it comes with increased complexity in encoding and decoding processes. In conclusion, this study provides insights into optimizing the representation of chess game states, offering potential applications in chess engines, game databases, and artificial intelligence research. The proposed methods offer a balance between space efficiency and computational overhead, paving the way for further advancements in the field.

Keywords: chess, optimisation, encoding, bit manipulation

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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Authors: Nuzhat Sharmin

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Human being is the most integral part of the nature and responsible for maintaining ecological balance both in rural and urban areas. But unfortunately, we are not doing our job with a holistic approach. The rapid growth of urbanization is making human life more isolated from greenery. Nowadays modern urban living involves sensory deprivation and overloaded stress. In many cities and towns of the world are expanding unabated in the name of urbanization and industrialization and in fact becoming jungles of concrete. Dhaka is one of the examples of such cities where open and green spaces are decreasing because of accommodating the overflow of population. This review paper has been prepared based on interviewing 30 teenagers, both male and female in Dhaka city. There were 12 open-ended questions in the questionnaire. For the literature review information had been gathered from scholarly papers published in various peer-reviewed journals. Some information was collected from the newspapers and some from fellow colleagues working around the world. Ideally about 25% of an urban area should be kept open or with parks, fields and/or plants and vegetation. But currently Dhaka has only about 10-12% open space and these also are being filled up rapidly. Old Dhaka has only about 5% open space while the new Dhaka has about 12%. Dhaka is now one of the most populated cities in the world. Accommodating this huge influx of people Dhaka is continuously losing its open space. As a result, children and teenagers are losing their interest in playing games and making friends, rather they are mostly occupied by television, gadgets and social media. It has been known from the interview that only 28% of teenagers regularly play. But the majority of them have to play on the street and rooftop for the lack of open space. On an average they are occupied with electronic devices for 8.3 hours/day. 64% of them has chronic diseases and often visit doctors. Most shockingly 35% of them claimed for not having any friends. Green space offers relief from stress. Areas of natural environment in towns and cities are theoretically seen providing setting for recovery and recuperation from anxiety and strains of the urban environment. Good quality green spaces encourage people to walk, run, cycle and play. Green spaces improve air quality and reduce noise, while trees and shrubbery help to filter out dust and pollutants. Relaxation, contemplation and passive recreation are essential to stress management. All city governments that are losing its open spaces should immediately pay attention to this aesthetic issue for the benefit of urban people. All kinds of development must be sustainable both for human being and nature.

Keywords: greenery, health, human, urban

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Authors: Keiko Yamauchi, Motoyuki Nakao, Yoko Ishihara

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The increase in the number of women with breast cancer in Japan has required hospitals to provide a higher quality of medicine so that patients are satisfied with the treatment they receive. However, patients’ satisfaction following breast cancer treatment has not been sufficiently studied. Hence, we investigated the factors influencing patient satisfaction following breast cancer treatment among Japanese women. These women underwent either breast-conserving surgery (BCS) (n = 380) or total mastectomy (TM) (n = 247). In March 2016, we conducted a cross-sectional internet survey of Japanese women with breast cancer in Japan. We assessed the following factors: socioeconomic status, cancer-related information, the role of medical decision-making, the degree of satisfaction regarding the treatments received, and the regret arising from the medical decision-making processes. We performed logistic regression analyses with the following dependent variables: extreme satisfaction with the treatments received, and regret regarding the medical decision-making process. For both types of surgery, the odds ratio (OR) of being extremely satisfied with the cancer treatment was significantly higher among patients who did not have any regrets compared to patients who had. Also, the OR tended to be higher among patients who chose to play a wanted role in the medical decision-making process, compared with patients who did not. In the BCS group, the OR of being extremely satisfied with the treatment was higher if, at diagnosis, the patient’s youngest child was older than 19 years, compared with patients with no children. The OR was also higher if patient considered the stage and characteristics of their cancer significant. The OR of being extremely satisfied with the treatments was lower among patients who were not employed on full-time basis, and among patients who considered the second medical opinions and medical expenses to be significant. These associations were not observed in the TM group. The OR of having regrets regarding the medical decision-making process was higher among patients who chose to play a role in the decision-making process as they preferred, and was also higher in patients who were employed on either a part-time or contractual basis. For both types of surgery, the OR was higher among patients who considered a second medical opinion to be significant. Regardless of surgical type, regret regarding the medical decision-making process decreases treatment satisfaction. Patients who received breast-conserving surgery were more likely to have regrets concerning the medical decision-making process if they could not play a role in the process as they preferred. In addition, factors associated with the satisfaction with treatment in BCS group but not TM group included the second medical opinion, medical expenses, employment status, and age of the youngest child at diagnosis.

Keywords: medical decision making, breast-conserving surgery, total mastectomy, Japanese

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Authors: Navah Z. Ratzon, Shlomit Cohen, Sigal Portnoy

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This work focuses on posture and risk factors for the musculoskeletal disorder in guitarists, which constitutes the largest group of musicians today. The source of the problems experienced by these musicians is linked to physical, psychosocial and personal risk factors. These muscular problems are referred to as Playing Related Musculoskeletal Disorder (PRMD). There is not enough research that specifically studies guitar players, and to the extent of our knowledge, there is almost no reference to the characteristics of their movement patterns while they play. This is in spite of the high prevalence of PRMD in this population. Kinematic research may provide a basis for the development of a prevention plan for this population and their unique characteristics of playing patterns. The aim of the study was to investigate the correlation between risk factors for PRMD among guitar players and self-reporting of pain in the skeletal muscles, and specifically to test whether there are differences in the kinematics of the upper body while playing in a sitting or standing posture. Twenty-five guitarists, aged 18-35, participated in the study. The methods included a motion analysis using a motion capture system, anthropometric measurements and questionnaires relating to risk factors. The questionnaires used were the Standardized Nordic Questionnaire for the Analysis of Musculoskeletal Symptoms and the Demand Control Support Questionnaire, as well as a questionnaire of personal details. All of the study participants complained of musculoskeletal pain in the past year; the most frequent complaints being in the left wrist. Statistically significant correlations were found between biodemographic indices and reports of pain in the past year and the previous week. No significant correlations were found between the physical posture while playing and reports of pain among professional guitarists. However, a difference was found in several kinematic parameters between seated and standing playing postures. In a majority of the joints, the joint angles while playing in a seated position were more extreme than those during standing. This finding may suggest a higher risk for musculoskeletal disorder while playing in a seated position. In conclusion, the results of the present research highlight the prevalence of musculoskeletal problems in guitar players and its correlation with various risk factors. The finding supports the need for intervention in the form of prevention through identifying the risk factors and addressing them. Relating to the person, to their occupation and environment, which are the basis of proper occupational therapy, can help meet this need.

Keywords: body posture, motion tracking, PRMD, guitarists

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Authors: Meless Gebrie Bore, Lin Perry, Xiaoyue Xu, Andargachew Kassa, Marilyn Cruickshank

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Background: Adolescents living with HIV (ALHIV) in Ethiopia face significant health challenges, particularly related to nutrition, which is essential for optimizing antiretroviral therapy (ART) outcomes. This population is vulnerable to nutritional deficiencies due to increased energy demands and the adverse effects of HIV, alongside rapid growth and low socio-economic status. Despite advances in ART, research on nutritional care for ALHIV in Ethiopia is limited. Integrated nutritional interventions are critical for improving health outcomes, yet comprehensive guidance is lacking. This study aimed to evaluate healthcare workers' practices in ART clinics, assess the nutritional status of ALHIV, and provide recommendations for enhancing nutritional care. Method: Cross-sectional surveys were conducted, recruiting 44 healthcare professionals and 384 ALHIV across ten public hospitals in Addis Ababa and Oromia regions. Participants were selected using purposive sampling for healthcare workers and proportionate random sampling for ALHIV engaged in ART services. Data was collected using a pre-tested structured questionnaire with quantitative and qualitative components facilitated by trained healthcare workers through the Kobo Toolbox program. Results: Findings revealed that while most healthcare workers conducted basic nutritional assessments, more sensitive methods were rarely used. Only 36.4% assessed dietary intake and 27.3% evaluated food security. Nutrition counseling was limited, with only 38.6% providing such services regularly. Health Care worker participants expressed dissatisfaction with the integration of nutrition services due to a lack of training and resources. Nutritional assessments revealed that 24.2% of ALHIV were classified as thin, 21.7% as stunted, and 34.9% as malnourished based on mid-upper arm circumference, with 19.4% experiencing severe acute malnutrition. These results highlight the urgent need and opportunities to improve nutritional support tailored to ALHIV-specific needs. Conclusion and Recommendations: Study findings identified evidence of substantial nutritional deficits and critical gaps in nutritional care for ALHIV in Ethiopian ART clinics. While basic assessment and counseling were generally practiced, limited use of more sensitive methods and inadequate integration of nutrition services hindered care effectiveness. To improve health outcomes, it is essential to enhance training for healthcare workers, develop standardized nutrition guidelines, and allocate resources effectively. Conducting further research with large, diverse samples and integrating comprehensive nutritional care alongside ART services will enable better matching of the nutritional needs of this vulnerable population.

Keywords: adolescents living with HIV(ALHIV), antiretroviral therapy (ART), HIV, Ethiopia, malnutrition, nutritional support, stunting, thinness

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Authors: Fleura Shkëmbi, Sevim Mustafa, Naim Fanaj

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Hypnosis, often known as cognitive therapy, is a sort of mind-body psychotherapy. A professional and certified hypnotist or hypnotherapist guides the patient into this extreme level of focus and relaxation during the session by utilizing verbal cues, repetition, and imagery. In recent years, hypnotherapy has gained popularity in the treatment of a variety of disorders, including anxiety and particular phobias. The term "phobia" is commonly used to define fear of a certain trigger. When faced with potentially hazardous situations, the brain naturally experiences dread. While a little dread here and there may keep us safe, phobias can drastically reduce our quality of life. In summary, persons who suffer from anxiety are considered to see particular environmental situations as dangerous, but those who do not suffer from anxiety do not. Hypnosis is essential in the treatment of anxiety disorders. Hypnosis can help patients minimize their anxiety symptoms. This broad concept has aided in the development of models and therapies for anxiety disorders such as generalized anxiety disorder, panic attacks, hypochondria, and obsessional disorders. Hypnosis techniques are supposed to be attentive and mental pictures, which is conceivable; this is why they're associated with improved working memory and visuospatial abilities. In this sense, the purpose of this study is to determine how effectively specific therapeutic methods perform in treating persons with anxiety and phobias. In addition to cognitive-behavioral therapy and other therapies, the approaches emphasized the use of therapeutic hypnosis. This study looks at the use of hypnosis and related psychotherapy procedures in the treatment of anxiety disorders. Following a discussion of the evolution of hypnosis as a therapeutic tool, neurobiological research is used to demonstrate the influence of hypnosis on the change of perception in the brain. The use of hypnosis in the treatment of phobias, stressful situations, and posttraumatic stress disorder is examined, as well as similarities between the hypnotic state and dissociative reactions to trauma. Through an extensive literature evaluation, this study will introduce hypnotherapy procedures that result in more successful anxiety and phobia treatment.

Keywords: anxiety, hypnosis, hypnotherapy, phobia, technique, state

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Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

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Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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Authors: Zahra R. Almansoor

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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.

Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker

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Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.

Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening

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Authors: Celine Shi Ying Lee, Jong Jian Lee

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Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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Authors: Anita Bajpai, Sarah Duan, Ashlee Erskine, Shehzein Khan, Raymond Kramer

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Introduction: This research focuses on exploring the beneficial effects if any, of Vitamin-D in reducing the need for supplemental oxygen among hospitalized COVID-19 patients. Two questions are investigated – Q1)Doeshaving a healthy level of baselineVitamin-D 25-OH (≥ 30ng/ml) help,andQ2) does administering Vitamin-D therapy after-the-factduring inpatient hospitalization help? Methods/Study Design: This is a comprehensive, retrospective, observational study of all inpatients at RUHS from March through December 2020 who tested positive for COVID-19 based on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs and rapid assay antigen test. To address Q1, we looked atall N1=182 patients whose baseline plasma Vitamin-D 25-OH was known and who needed supplemental oxygen. Of this, a total of 121 patients had a healthy Vitamin-D level of ≥30 ng/mlwhile the remaining 61 patients had low or borderline (≤ 29.9ng/ml)level. Similarly, for Q2, we looked at a total of N2=893 patients who were given supplemental oxygen, of which713 were not given Vitamin-D and 180 were given Vitamin-D therapy. The numerical value of the maximum amount of oxygen flow rate(dependent variable) administered was recorded for each patient. The mean values and associated standard deviations for each group were calculated. Thesetwo sets of independent data served as the basis for independent, two-sample t-Test statistical analysis. To be accommodative of any reasonable benefitof Vitamin-D, ap-value of 0.10(α< 10%) was set as the cutoff point for statistical significance. Results: Given the large sample sizes, the calculated statistical power for both our studies exceeded the customary norm of 80% or better (β< 0.2). For Q1, the mean value for maximumoxygen flow rate for the group with healthybaseline level of Vitamin-D was 8.6 L/min vs.12.6L/min for those with low or borderline levels, yielding a p-value of 0.07 (p < 0.10) with the conclusion that those with a healthy level of baseline Vitamin-D needed statistically significant lower levels of supplemental oxygen. ForQ2, the mean value for a maximum oxygen flow rate for those not administered Vitamin-Dwas 12.5 L/min vs.12.8L/min for those given Vitamin-D, yielding a p-valueof 0.87 (p > 0.10). We thereforeconcludedthat there was no statistically significant difference in the use of oxygen therapy between those who were or were not administered Vitamin-D after-the-fact in the hospital. Discussion/Conclusion: We found that patients who had healthy levels of Vitamin-D at baseline needed statistically significant lower levels of supplemental oxygen. Vitamin-D is well documented, including in a recent article in the Lancet, for its anti-inflammatory role as an adjuvant in the regulation of cytokines and immune cells. Interestingly, we found no statistically significant advantage for giving Vitamin-D to hospitalized patients. It may be a case of “too little too late”. A randomized clinical trial reported in JAMA also did not find any reduction in hospital stay of patients given Vitamin-D. Such conclusions come with a caveat that any delayed marginal benefits may not have materialized promptly in the presence of a significant inflammatory condition. Since Vitamin-D is a low-cost, low-risk option, it may still be useful on an inpatient basis until more definitive findings are established.

Keywords: COVID-19, vitamin-D, supplemental oxygen, vitamin-D in primary care

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Maria Lucia G. Lourenco, Viviane Y. Hibaru, Keylla H. N. P. Pereira, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Isosporiasis is an affliction caused by coccidial protozoa belonging to genera Isospora spp. or Cystoisospora spp., which may parasitize the small and large intestines of dogs, of which neonates and young animals present higher risk of infection. This study aims at reporting a case of isosporiasis in neonate Pitbull dogs, as well as the diagnosis and treatment. Seven Pitbull puppies were admitted to the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, São Paulo, Brazil, with history of yellowish diarrhea without mucus or blood for the past two days. The animals were five days old. The history of the mother, a primiparous two-year-old, revealed that she was properly vaccinated, not de-wormed and did not present diarrhea. The clinical examination revealed that the neonates weighted between 308 and 360 grams, and presented normal reflexes, moderate dehydration, body temperatures between 36.8 and 37.2 ºC, blood sugar between 103 and 124 mg/dL and normal appetite. A full blood count and a parasitology assay were performed to aid in the diagnosis. The full blood count detected eosinophilia, without any other relevant alterations. The parasitology assay (Willis-Molly & Faust) revealed the presence of Cystoisospora spp. The treatment was instituted with heated fluid therapy with Ringer’s Lactate (4 mL/100 g, subcutaneous) and antibiotic therapy with sulfamethoxazole-trimethoprim (15 mg/kg, orally) every 12 hours for ten days. The mother and other dogs that came in contact with the newborns were also treated. The environment was disinfected for 10 minutes with 1.6% quaternary ammonium. After 10 days, the newborns presented normal clinical signs and no alterations in the full blood count. Isosporiasis is an affliction with high mortality rates in litters that should be diagnosed and treated as soon as possible to increase the survival rates in these patients.

Keywords: Cystoisospora spp., neonatal infection, puppies, diarrhea,

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