Search results for: therapeutic design

Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Kazumoto Tanaka, Takayuki Fujino

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Sports games conducted as a group are a form of therapeutic exercise for aged people with decreased strength and for people suffering from permanent damage of stroke and other conditions. However, it is difficult for patients with different athletic abilities to play a game on an equal footing. This study specifically examines a computer video game designed for therapeutic exercise, and a game system with support given depending on athletic ability. Thereby, anyone playing the game can participate equally. This video-game, to be specific, is a popular variant of balloon volleyball, in which players hit a balloon by hand before it falls to the floor. In this game system, each player plays the game watching a monitor on which the system displays tailor-made video-game images adjusted to the person’s athletic ability, providing players with player-adaptive assist support. We have developed a multiplayer game system with an image generation technique for the tailor-made video-game and conducted tests to evaluate it.

Keywords: therapeutic exercise, computer video game, disability-adaptive assist, tailor-made video-game image

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Authors: P. S. Jagadeesh Kumar, Mingmin Pan, Yang Yung, Tracy Lin Huan

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Glaucoma is a group of visual maladies represented by the scheduled optic nerve neuropathy; means to the increasing dwindling in vision ground, resulting in loss of sight. In this paper, a novel support vector machine based retinal therapeutic for glaucoma using machine learning algorithm is conservative. The algorithm has fitting pragmatism; subsequently sustained on correlation clustering mode, it visualizes perfect computations in the multi-dimensional space. Support vector clustering turns out to be comparable to the scale-space advance that investigates the cluster organization by means of a kernel density estimation of the likelihood distribution, where cluster midpoints are idiosyncratic by the neighborhood maxima of the concreteness. The predicted planning has 91% attainment rate on data set deterrent on a consolidation of 500 realistic images of resolute and glaucoma retina; therefore, the computational benefit of depending on the cluster overlapping system pedestal on machine learning algorithm has complete performance in glaucoma therapeutic.

Keywords: machine learning algorithm, correlation clustering mode, cluster overlapping system, glaucoma, kernel density estimation, retinal therapeutic

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Authors: Jenny Jin

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Background: The therapeutic use of cannabis for cancer symptom control in Australia is gaining momentum, reflecting a broader global acceptance of its medicinal potential. Objective: This overview examines the historical context, current regulations, and clinical applications of cannabis in oncology within Australia. Methods: A historical analysis outlines the ancient and 19th-century medicinal uses of cannabis, followed by its prohibition in the early 20th century and subsequent resurgence in the late 20th century. The current legal framework under the therapeutic gods administration (TGA) is discussed. Results: Research indicates that cannabinoids, particularly THC and CBD, effectively alleviate pain, reduce chemotherapy-induced nausea and vomiting, stimulate appetite, and enhance overall quality of life for cancer patients. Despite these benefits, challenges such as dosing standardization, stigma, and access barriers persist. Conclusion: Continued clinical research, policy development, and educational initiatives are essential to optimize the use of cannabis in cancer care. A patient-centred approach, emphasizing interdisciplinary collaboration and informed decision-making, is crucial for improving therapeutic outcomes in this evolving field.

Keywords: historical context of cannabis, symptom control in oncology patients, therapeutic benefits, outcome and future

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Authors: Mohammad Hamed Asosheh

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The development of nanobiomaterials has opened new avenues in the field of biomedical engineering, offering unparalleled possibilities for advanced therapeutic applications. This study explores the synthesis and characterization of a distinct class of nanobiomaterials designed to enhance drug delivery systems and support tissue engineering. By integrating biodegradable polymers with bioactive nanoparticles, we have engineered a multifunctional platform that ensures controlled drug release, targeted delivery, and improved biocompatibility. Our findings demonstrate that these nanobiomaterials not only exhibit excellent mechanical properties but also promote cell proliferation and differentiation, making them ideal candidates for regenerative medicine. Furthermore, in vitro and in vivo assessments reveal that the engineered materials significantly reduce cytotoxicity while enhancing the therapeutic efficacy of encapsulated drugs. This research presents a promising approach to addressing current challenges in drug delivery and tissue regeneration, with the potential to revolutionize the treatment of chronic diseases and injury repair. Future work will focus on optimizing the material composition for specific clinical applications and conducting large-scale studies to evaluate long-term safety and effectiveness.

Keywords: nanobiomaterials, drug delivery systems, therapeutic efficacy, bioactive nanoparticles

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Sang Guen Kim, Sib Sankar Giri, Jin Woo Jun, Saekil Yun, Hyoun Joong Kim, Sang Wha Kim, Jung Woo Kang, Se Jin Han, Se Chang Park

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Emerging of the super bacteria, bacteriophages are considered to be as an alternative to antibiotics. As the demand of phage increased, economical and large production of phage is becoming one of the critical points. For the therapeutic use, what is important is to eradicate the pathogenic bacteria as fast as possible, so higher concentration of phages is generally needed for effective therapeutic function. On the contrary, for the maximum production, bacteria work as a phage producing factory. As a microbial cell factory, bacteria is needed to last longer producing the phages without eradication. Consequently, killing the bacteria fast has a negative effect on large production. In this study, Multiplicity of Infection (MOI) was manipulated based on initial bacterial inoculation and used phage pAh-6C which has therapeutic effect against Aeromonas hydrophila. 1, 5 and 10 percent of overnight bacterial culture was inoculated and each bacterial culture was co-cultured with the phage of which MOI of 0.01, 0.0001, and 0.000001 respectively. Simply changing the initial MOI as well as bacterial inoculation concentration has regulated the production quantity of the phage without any other changes to culture conditions. It is anticipated that this result can be used as a foundational data for mass production of lytic bacteriophages which can be used as the therapeutic bio-control agent.

Keywords: bacteriophage, multiplicity of infection, optimization, Aeromonas hydrophila

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Authors: Pierce Radecki, Pulkit Malik, Bharath Ramaswamy, Ben Shapiro

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The ability to effectively design and test magnetic nanoparticles for controlled movement has been an elusive goal in the design of these particles. Magnetic nanoparticles of various characteristics have been created for use towards therapeutic effects, however the challenge of designing for controlled movement remains unmet. A step towards design in this aspect is a first principles model that captures and predicts the behaviors of particles in a magnetic field. The model is governed by four forces acting on the particles, the magnetic gradient, the dipole-dipole forces, the steric forces, and the viscous drag force. The particles are multi-core or single core, and incorporate a preferred magnetization axis. Particles exhibit behaviors, such as chaining, in simulations that are similar to those witnessed through experimentation. Currently, experimental results are being compared to the modeling results for verification of the model, through the analysis of chaining behaviors. This modeling system will be used in designing magnetic nanoparticles for specific chaining and movement behaviors.

Keywords: controlled movement, modeling, magnetic nanoparticles, nanoparticle design

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Authors: Masoume Pourmohamadreza-Tajrishi, Parviz Azadfallah

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Autism spectrum disorders (ASD) involve myriad aberrant perceptual, cognitive, linguistic, and social behaviors. The term spectrum emphasizes that the disabilities associated with ASD fall on a continuum from relatively mild to severe. People with ASD may display stereotyped behaviors such as twirling, spinning objects, flapping the hands, and rocking. The individuals with ASD exhibit communication problems due to repetitive/restricted behaviors. Children with ASD who lack the motivation to learn, who do not enjoy physical challenges, or whose sensory perception results in confusing or unpleasant feedback from movement may not become sufficiently motivated to practice motor activities. As a result, they may show both a delay in developing certain motor skills. Additionally, attention is an important component of learning. As far as children with ASD have problems in joint attention, many education-based programs are needed to consider some aspects of attention and motor activities development for students with ASD. These programs focus on the basic movement skills that are crucial for the future development of the more complex skills needed in games, dance, sports, gymnastics, active play, and recreational physical activities. The purpose of the present research was to determine the effectiveness of therapeutic exercise on motor skills and attention of male students with ASD. This was an experimental study with a control group. The population consisted of 8-10 year-old male students with ASD and 30 subjects were selected randomly from an available center suitable for the children with ASD. They were evaluated by the Basic Motor Ability Test (BMAT) and Persian version of computerized Stroop color-word test and randomly assigned to an experimental and control group (15 students in per group). The experimental group participated in 16 therapeutic exercise sessions and received therapeutic exercise program (twice a week; each lasting for 45 minutes) designed based on the Spark motor program while the control group did not. All subjects were evaluated by BMAT and Stroop color-word test after the last session again. The collected data were analyzed by using multivariate analysis of covariance (MANCOVA). The results of MANCOVA showed that experimental and control groups had a significant difference in motor skills and at least one of the components of attention (correct responses, incorrect responses, no responses, the reaction time of congruent words and reaction time of incongruent words in the Stroop test). The findings showed that the therapeutic exercise had a significant effect on motor skills and all components of attention in students with ASD. We can conclude that the therapeutic exercise led to promote the motor skills and attention of students with ASD, so it is necessary to design or plan such programs for ASD students to prevent their communication or academic problems.

Keywords: Attention, autism spectrum disorder, motor skills, therapeutic exercise

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Authors: M. G. Nasuruddin, S. Ishak

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This paper deals with the traditional Malay healing ritualistic ceremony known as Main Puteri. This non-invasive intervention uses the vehicle of performance to administer the healing process. It employs the performance elements of Makyung, that is, music, movements/dance, and dramatic dialogue to heal psychosomatic maladies. There are two perspectives to this therapeutic healing process, one traditional and the other scientific. From the traditional perspective, the psychosomatic illness is attributed to the infestations/possessions by malevolent spirits. To heal such patients, these spirits must be exorcised through placating them by making offerings. From the scientific perspective, the music (sonic orders), movements (kinetic energy), and smell (olfactory) connect with the brain waves to release the chemicals that would activate the internal healing energy. Currently, in Main Puteri, the therapeutic healing ritual is no longer relevant as modern clinical medicine has proven to be more effective. Thus, Main Puteri is an anachronism in today’s technologically advanced Malaysia.

Keywords: exorcism, main puteri, shamans, therapeutic healing

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Authors: Sonia Nemakallu, Pota Kalima

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Introduction: Vancomycin is a glycopeptide antibiotic, commonly used to treat gram-positive bacteraemia. It has been increasingly used in the critical care setting due to an increased awareness of resistant gram positive organisms. In Edinburgh both tertiary hospitals, The Western General Hospital and The Royal Infirmary Of Edinburgh, commonly use Vancomycin for a variety of infections. Administration of Vancomyicn in these hospitals is by continuous infusion as it is thought to maintain serum concentrations easier and is a simpler monitoring system. Purpose: The aim of the study was to evaluate the efficacy and reliability in which Vancomycin is used. Material and Methods: A retrospective study, over a 6-month period from January 2014 to June 2014. 91 admissions were included, all received Vancomycin by continuous infusion during their critical care stay. Results: The number one use for Vancomycin in critical care settings was in the treatment of ventilator or hospital-acquired pneumonia. Only 3% of population had MRSA. 49% of admissions were not therapeutic on day 1 post loading dose. Of those that were therapeutic on day 1 post loading dose, 39% of admissions showed no organisms in any cultures taken, 42% had organisms sensitive to Vancomycin and 19% had only organisms resistant to Vancomycin. Those that were not therapeutic on day 1 showed similar organism sensitivities. 15% of admissions had Vancomycin levels above 25 (levels should be maintained between 15-25). An increase in creatinine was proportionally seen with an increase in Vancomycin levels. Conclusion: Within Edinburgh Vancomycin is being overused in the critical care setting with only 3% of the population having highly resistant organisms. Continuous infusion have not ruled out the complexity of maintaining therapeutic levels, with a large proportion of patients not being therapeutic on day 1. Further research is also required into the nephrotoxic effects of using higher doses of Vancomycin.

Keywords: Vancomycin, continuous infusion, multi resistant organisms, sepsis, renal toxicity

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Authors: Sakshi Kaul, Sundeep Verma

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The focus of the current paper is to evaluate the therapeutic power of words. This will be done by critically evaluating the impact reading, writing and storytelling have on individuals. When we read, tell or listen to a story we are exercising our imagination. Imagination becomes the source of activation of thoughts and actions. This enables and helps the reader, writer or the listener to express the suppressed emotions or desires. The stories told, untold may bring various human emotions and attributes to forth such as hope, optimism, fear, happiness. Each story narrated evokes different emotions, at times they help us unravel ourselves in the world of the teller thereby bringing solace. Stories heard or told add to individual’s life by creating a community around, giving wings of thoughts that enable individual to be more imaginative and creative thereby fostering positively and happiness. Reading if looked at from the reader’s point of view can broaden the horizon of information and ideas about facts and life laws giving more meaning to life. From ‘once upon a time’ to ‘to happily ever after’, all that stories talk about is life’s learning. The power of words sometimes may be negated, this paper would reiterate the power of words by critically evaluating how words can become powerful and therapeutic in various structures and forms in the society. There is a story behind every situation, action and reaction. Hence it is of prime importance to understand each story, to enable a person to deal with whatever he or she may be going through. For example, if a client is going through some trauma in his or her life, the counsellor needs to know exactly what is the turmoil that is being faced so that the client can be assisted accordingly. Counselling is considered a process of healing through words or as Talk therapy, where merely through words we try to heal the client. In a counselling session, the counsellor focuses on working with the clients to bring a positive change. The counsellor allows the client to express themselves which is referred to as catharsis. The words spoken, written or heard transcend to heal and can be therapeutic. The therapeutic power of words has been seen in various cultural practices and belief systems. The underlining belief that words have the power to heal, save and bring change has existed from ages. Many religious and spiritual practices also acclaim the power of the words. Through this empirical paper, we have tried to bring to light how reading, writing, and storytelling have been used as mediums of healing and have been therapeutic in nature.

Keywords: reading, storytelling, therapeutic, words

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Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

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Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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Authors: Debabrata Biswas

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The current trend in the development of antibiotic resistance by multiple bacterial pathogens has resulted in a troubling loss of effective antibiotic options for human. The emergence of multi-drug-resistant pathogens has necessitated higher dosages and combinations of multiple antibiotics, further exacerbating the problem of antibiotic resistance. Zoonotic bacterial pathogens, such as Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (such as enterohaemorrhagic E. coli or EHEC), and Listeria are the most common and predominant foodborne enteric infectious agents. It was observed that these pathogens gained/developed their ability to survive in the presence of antibiotics either in farm animal gut or farm environment and researchers believe that therapeutic and sub-therapeutic antibiotic use in farm animal production might play an important role in it. The mechanism of action of antimicrobial components used in farm animal production in genomic interplay in the gut and farm environment, has not been fully characterized. Even the risk of promoting the exchange of mobile genetic elements between microbes specifically pathogens needs to be evaluated in depth, to ensure sustainable farm animal production, safety of our food and to mitigate/limit the enteric infection with multiple antibiotic resistant bacterial pathogens. Due to the consumer’s demand and considering the current emerging situation, many countries are in process to withdraw antibiotic use in farm animal production. Before withdrawing use of the sub-therapeutic antibiotic or restricting the use of therapeutic antibiotics in farm animal production, it is essential to find alternative natural antimicrobials for promoting the growth of farm animal and/or treating animal diseases. Further, it is also necessary to consider whether that compound(s) has the potential to trigger the acquisition or loss of genetic materials in zoonotic and any other bacterial pathogens. Development of alternative therapeutic and sub-therapeutic antimicrobials for farm animal production and food processing and preservation and their effective implementation for sustainable strategies for farm animal production as well as the possible risk for horizontal gene transfer in major enteric pathogens will be focus in the study.

Keywords: food safety, natural antimicrobial, sustainable farming, antibiotic resistance

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Authors: An Guo, Hieyong Jeong, Tianyi Wang, Na Li, Yuko Ohno

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Acupuncture, known as sensory simulation, has been used to treat various disorders for thousands of years. However, present studies had not addressed approaches for noninvasive measurement in order to evaluate therapeutic effect of acupuncture. The purpose of this study is to propose a noninvasive method to evaluate acupuncture by measuring facial temperature through thermal image. Three human subjects were recruited in this study. Each subject received acupuncture therapy for 30 mins. Acupuncture needles (Ø0.16 x 30 mm) were inserted into Baihui point (DU20), Neiguan points (PC6) and Taichong points (LR3), acupuncture needles (Ø0.18 x 39 mm) were inserted into Tanzhong point (RN17), Zusanli points (ST36) and Yinlingquan points (SP9). Facial temperature was recorded by an infrared thermometer. Acupuncture therapeutic effect was compared pre- and post-acupuncture. Experiment results demonstrated that facial temperature changed according to acupuncture therapeutic effect. It was concluded that proposed method showed high potential to evaluate acupuncture by noninvasive measurement of facial temperature.

Keywords: acupuncture, facial temperature, noninvasive evaluation, thermal image

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Authors: Svilen Dimitrov, Manthan Pancholi, Norbert Schmitz, Didier Stricker

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This paper presents the end-to-end development of a wearable motion sensing harness consisting of computational unit and four inertial measurement units to control three smartphone therapeutic games for children. The inertial data is processed in real time to obtain lower body motion information like knee raises, feet taps and squads. By providing a Wi-Fi connection interface the sensor harness acts wireless remote control for smartphone applications. By performing various lower body movements the users provoke corresponding game state changes. In contrary to the current similar offers, like Nintendo Wii Remote, Xbox Kinect and Playstation Move, this product, consisting of the sensor harness and the applications on top of it, are fully wearable, which means they do not rely on the user to be bound to concrete soft- or hardwareequipped space.

Keywords: wearable harness, inertial measurement units, smartphone therapeutic games, motion tracking, lower-body activity monitoring

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Authors: Arash Sepehri bonab

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One of the regions of critical development in medical devices has been the part of the software - as an indispensable component of a therapeutic device, as a standalone device, and more as of late, as applications on portable gadgets. The chance related to a breakdown of the standalone computer program utilized inside healthcare is in itself not a model for its capability or not as a medical device. It is, subsequently, fundamental to clarify a few criteria for the capability of a stand-alone computer program as a medical device. The number of computer program items and therapeutic apps is persistently expanding and so as well is used in wellbeing education (e. g., in clinics and doctors' surgeries) for determination and treatment. Within the last decade, the use of information innovation in healthcare has taken a developing part. In reality, the appropriation of an expanding number of computer devices has driven several benefits related to the method of quiet care and permitted simpler get to social and health care assets. At the same time, this drift gave rise to modern challenges related to the usage of these modern innovations. The program utilized in healthcare can be classified as therapeutic gadgets depending on the way they are utilized and on their useful characteristics. In the event that they are classified as therapeutic gadgets, they must fulfill particular directions. The point of this work is to show a computer program improvement system that can permit the generation of secure and tall, quality restorative gadget computer programs and to highlight the correspondence between each program advancement stage and the fitting standard and/or regulation.

Keywords: medical devices, regulation, software, development, healthcare

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Authors: Gloria Pinilla, Jose Manuel Baena, Patricia Gálvez-Martín, Juan Antonio Marchad

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Cartilage is a dense connective tissue with limited self-repair properties. Currently, the therapeutic use of autologous or allogenic chondrocytes makes up an alternative therapy to the pharmacological treatment. The design of a bioprinted 3D cartilage with chondrocytes and biodegradable biomaterials offers a new therapeutic alternative able of bridging the limitations of current therapies in the field. We have developed an enhanced printing processes-Injection Volume Filling (IVF) to increase the viability and survival of the cells when working with high-temperature thermoplastics without the limitation of the scaffold geometry in contact with cells. We have demonstrated the viability of the printing process using chondrocytes for cartilage regeneration. This development will accelerate the clinical uptake of the technology and overcomes the current limitation when using thermoplastics as scaffolds. An alginate-based hydrogel combined with human chondrocytes (isolated from osteoarthritis patients) was formulated as bioink-A and the polylactic acid as bioink-B. The bioprinting process was carried out with the REGEMAT V1 bioprinter (Regemat 3D, Granada-Spain) through a IVF. The printing capacity of the bioprinting plus the viability and cell proliferation of bioprinted chondrociytes was evaluated after five weeks by confocal microscopy and Alamar Blue Assay (Biorad). Results showed that the IVF process does not decrease the cell viability of the chondrocytes during the printing process as the cells do not have contact with the thermoplastic at elevated temperatures. The viability and cellular proliferation of the bioprinted artificial 3D cartilage increased after 5 weeks. In conclusion, this study demonstrates the potential use of Regemat V1 for 3D bioprinting of cartilage and the viability of bioprinted chondrocytes in the scaffolds for application in regenerative medicine.

Keywords: cartilage regeneration, bioprinting, bioink, scaffold, chondrocyte

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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Authors: Sadeq Al Yaari, Fayza Alhammadi, Ayman Al Yaari, Montaha Al Yaari, Aayah Al Yaari, Adham Al Yaari, Sajedah Al Yaari, Saleh Al Yami

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Background: There has been a debate in the literature over the years as to whether or not MossTalk Words program fits Arab Broca’s aphasics (BAs) due to that language differences and also the fact that the technique has not yet been used for aphasics with semantic dementia (SD aphasics). Aims: To oversimplify the above mentioned debate slightly for purposes of exposition, the purpose of the present study is to investigate the “usability” of this program as well as pictures and community as therapeutic techniques for both Arab BAs and SD aphasics. Method: The subjects of this study are two Saudi aphasics (53 and 57 years old, respectively). The former suffers from Broca’s aphasia due to a stroke, while the latter suffers from semantic dementia. Both aphasics can speak English and have used the Moss Talk Words program in addition to intensive picture-naming therapeutic sessions for two years. They were tested by one of the researchers four times (a time per six months). The families of the two subjects, in addition to their relatives and friends, played a major part in all therapeutic sessions. Conclusion: Results show that in averages across the entire therapeutic sessions, MossTalk Words program was clearly found more effective in modeling BAs’ pronunciation than that of SD aphasic. Furthermore, picture-naming intensive exercises in addition to the positive role of the community members played a major role in the progress of the two subjects’ performance.

Keywords: moss talk words, program, technique, Broca’s aphasia, semantic dementia, subjects, picture, community

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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Authors: Kuan-Wu Lin, Tsu-Wu Hu

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In recent years, product design has already begun to comfort and humanize, and for different user needs to design products, In particular, closer relationship with the people of the products, Such as headphones and other consumer electronics products. In this study, will for general comfort design principles and field survey results through the use of a headset, including adolescents, young and middle-aged groups such as three users, Further identify the general design principles belong to the headset comfortable design. The study results will include the significance of headphones design and differences between product design principles, Provide the basis for future product design.

Keywords: wearing type headphones , comfort degree design, general design principles, product design

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

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Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

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Authors: Talita Veldsman, Elzette Fritz

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Many children attending special education present with sensory integration difficulties that hamper their learning and behaviour. These learners can benefit from therapeutic interventions as part of their classroom curriculum that can address sensory development and allow for holistic development to take place. A research study was conducted by utilizing socio-drama as a therapeutic intervention in the classroom in order to develop sensory integration skills. The use of socio-drama as therapeutic intervention proved to be a successful multi-disciplinary approach where education and psychology could build a bridge of growth and integration. The paper describes how socio-drama was used in the classroom and how these sessions were designed. The research followed a qualitative approach and involved six Afrikaans-speaking children attending special secondary school in the age group 12-14 years. Data collection included observations during the session, reflective art journals, semi-structured interviews with the teacher and informal interviews with the adolescents. The analysis found improved self-confidence, better social relationships, sensory awareness and self-regulation in the participants after a period of a year.

Keywords: education, sensory integration, sociodrama, classroom intervention, psychology

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Authors: Semiu Bello

Abstract:

Since the discovery of HIV/AIDS in 1981, it has been a major global challenge and its ravaging consequences have had negative imprints on both the affected and infected people. The challenge of HIV/AIDS does not only affect the developing countries of the world, the developed nations have had their share of the experiences. The disease has, therefore, attracted the attentions of national governments and international donor agencies with huge financial investments toward the eradication of the virus and its global menace. Socially, however, people living with HIV/AIDS have had to battle with an array of social challenges in regards to the infection; the social stigmas, which seem to be more prevalent in underdeveloped and developing societies. The social stigmas with which people living with HIV/AIDS have suffered from include, but not limited, to social isolation, group avoidance, loss of jobs, public ridicule and non-appointment to official and government positions. Given this background, this study examines the roles of therapeutic communication otherwise called patient-provider communication within a clinical environment, focusing on Olabisi Onabanjo University Teaching Hospital (OOUTH) Sagamu, Nigeria as a case study. In other words, this study will investigate the level of interpersonal communication, interactions, and relationships that often take place between people living with HIV/AIDS and health care providers including doctors, nurses and social workers. This study will methodologically adopt the in-depth interview to interview six members of people living with HIV/AIDS at OOUTH. The dimensions of the data will determine the policy prescriptions of this study, which as envisage, may contribute to the improved use of therapeutic communication by health care providers and may thereof improve the psychology of people living with HIV/AIDS in the face of any social stigma.

Keywords: health care providers, people living with HIV/AIDS, social stigma, therapeutic communication

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Authors: Kalpana Singh, Nikita Katiyar

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This research investigates the impact of Raga Bhairavi, a prominent musical scale in Indian classical music, on the mood and basic physiological parameters of research scholars at the University of Lucknow - India. The study focuses on the potential therapeutic effects of listening to Raga Bhairavi during morning hours. A controlled experimental design is employed, utilizing self-reporting tools for mood assessment and monitoring physiological indicators such as heart rate, oxygen saturation levels, body temperature and blood pressure. The hypothesis posits that exposure to Raga Bhairavi will lead to positive mood modulation and a reduction in physiological stress markers among research scholars. Data collection involves pre and post-exposure measurements, providing insights into the immediate and cumulative effects of the musical intervention. The study aims to contribute valuable information to the growing field of music therapy, offering a potential avenue for enhancing the well-being and productivity of individuals engaged in intense cognitive activities. Results may have implications for the integration of music-based interventions in academic and research environments, fostering a conducive atmosphere for intellectual pursuits.

Keywords: bio-musicology, classical music, mood assessment, music therapy, physiology, Raga Bhairavi

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