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ß-Thalassemia (BT) is one of the most common genetic diseases worldwide and is caused by mutations affecting ß-globin production. The only curative treatment is allogenic hematopoietic stem/progenitor cells (HSPCs) transplantation, an approach limited by compatible donor availability and immunological complications. Therefore, transplantation of autologous, genetically-modified HSPCs is an attractive therapeutic option. However, current gene therapy strategies based on the use of lentiviral vectors are not equally effective in all patients and CRISPR/Cas9 nuclease-based strategies raise safety concerns. Thus, base editing strategies aiming to correct the genetic defect in patients' HSPCs could provide safe and effective treatment. Here, we developed a strategy to correct one of the most prevalent BT mutations (IVS1-110 [G>A]) using the SpRY-ABE8e base editor. RNA delivery of the base editing system was safe and led to â¼80% of gene correction in the HSPCs of patients with BT without causing dangerous double-strand DNA breaks. In HSPC-derived erythroid populations, this strategy was able to restore ß-globin production and correct inefficient erythropoiesis typically observed in BT both in vitro and in vivo. In conclusion, this proof-of-concept study paves the way for the development of a safe and effective autologous gene therapy approach for BT.
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Talassemia beta , Humanos , Talassemia beta/genética , Talassemia beta/terapia , Edição de Genes , Sistemas CRISPR-Cas , Mutação , Globinas beta/genéticaRESUMO
Fetal hemoglobin (HbF) reactivation expression through CRISPR-Cas9 is a promising strategy for the treatment of sickle cell disease (SCD). Here, we describe a genome editing strategy leading to reactivation of HbF expression by targeting the binding sites (BSs) for the lymphoma-related factor (LRF) repressor in the γ-globin promoters. CRISPR-Cas9 treatment in healthy donor (HD) and patient-derived HSPCs resulted in a high frequency of LRF BS disruption and potent HbF synthesis in their erythroid progeny. LRF BS disruption did not impair HSPC engraftment and differentiation but was more efficient in SCD than in HD cells. However, SCD HSPCs showed a reduced engraftment and a myeloid bias compared with HD cells. We detected off-target activity and chromosomal rearrangements, particularly in SCD samples (likely because of the higher overall editing efficiency) but did not impact the target gene expression and HSPC engraftment and differentiation. Transcriptomic analyses showed that the editing procedure results in the up-regulation of genes involved in DNA damage and inflammatory responses, which was more evident in SCD HSPCs. This study provides evidence of efficacy and safety for an editing strategy based on HbF reactivation and highlights the need of performing safety studies in clinically relevant conditions, i.e., in patient-derived HSPCs.
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In this guide we provide instructions and recommendations about creating and running escape rooms for healthcare education. In recent years there has been a growing interest in adopting escape rooms as an educational tool to be included in healthcare curricula, and we attempt to explain why and how these tools are fit for the particularities of this type of education. We first describe the steps that a design team will have to follow to create an educational escape room from scratch, from core characteristics like target audience and learning goals to actual puzzle design and testing. We then continue by providing recommendations to operators and lecturers about how to run such escape room as part of an overall teaching session that also includes a lecture, briefing, debriefing and evaluation. We finalise this guide by listing a set of tools for validating and evaluating these types of escape rooms.
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Motor neuron diseases are untreatable with common pharmacological approaches. Spinal muscular atrophy (SMA) is caused by SMN1 gene mutations leading to lowered SMN expression. Symptoms are alleviated in infants with a higher copy number of the SMN2 gene, which, however, displays a splicing defect resulting in low SMN levels. Amyotrophic lateral sclerosis (ALS) is caused by a number of mutations, with C9orf72 repeat expansions the most common genetic cause and SOD1 gain-of-function mutations the first genetic cause identified for this disease. Genetic therapies based on oligonucleotides that enhance SMN2 splicing and SMN production or lower SOD1 expression have shown promise in initial clinical trials for individuals with SMA and ALS harboring SOD1 mutations, respectively. Gene addition/silencing approaches using adeno-associated viruses (AAVs) are also currently under clinical investigation in trials for SMA and ALS. Here we provide a brief overview of these efforts and their advantages and challenges. We also review genome editing approaches aimed at correcting the disease-causing mutations or modulating the expression of genetic modifiers, e.g., by repairing SOD1 mutations or the SMN2 splicing defect or deleting C9orf72 expanded repeats. These studies have shown promising results to approach therapeutic trials that should significantly lower the progression of these deadly disorders.
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Esclerose Lateral Amiotrófica , Atrofia Muscular Espinal , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , Edição de Genes , Humanos , Lactente , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/terapia , Oligonucleotídeos/metabolismo , Splicing de RNA , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismoRESUMO
BACKGROUND: This article presents the system architecture and validation of the NeuroSuitUp body-machine interface (BMI). The platform consists of wearable robotics jacket and gloves in combination with a serious game application for self-paced neurorehabilitation in spinal cord injury and chronic stroke. METHODS: The wearable robotics implement a sensor layer, to approximate kinematic chain segment orientation, and an actuation layer. Sensors consist of commercial magnetic, angular rate and gravity (MARG), surface electromyography (sEMG), and flex sensors, while actuation is achieved through electrical muscle stimulation (EMS) and pneumatic actuators. On-board electronics connect to a Robot Operating System environment-based parser/controller and to a Unity-based live avatar representation game. BMI subsystems validation was performed using exercises through a Stereoscopic camera Computer Vision approach for the jacket and through multiple grip activities for the glove. Ten healthy subjects participated in system validation trials, performing three arm and three hand exercises (each 10 motor task trials) and completing user experience questionnaires. RESULTS: Acceptable correlation was observed in 23/30 arm exercises performed with the jacket. No significant differences in glove sensor data during actuation state were observed. No difficulty to use, discomfort, or negative robotics perception were reported. CONCLUSIONS: Subsequent design improvements will implement additional absolute orientation sensors, MARG/EMG based biofeedback to the game, improved immersion through Augmented Reality and improvements towards system robustness.
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Exoesqueleto Energizado , Reabilitação Neurológica , Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Dispositivos Eletrônicos Vestíveis , HumanosRESUMO
BACKGROUND: Globally, online and local area network-based (LAN) digital education (ODE) has grown in popularity. Blended learning is used by ODE along with traditional learning. Studies have shown the increasing potential of these technologies in training medical doctors; however, the evidence for its effectiveness and cost-effectiveness is unclear. OBJECTIVE: This systematic review evaluated the effectiveness of online and LAN-based ODE in improving practicing medical doctors' knowledge, skills, attitude, satisfaction (primary outcomes), practice or behavior change, patient outcomes, and cost-effectiveness (secondary outcomes). METHODS: We searched seven electronic databased for randomized controlled trials, cluster-randomized trials, and quasi-randomized trials from January 1990 to March 2017. Two review authors independently extracted data and assessed the risk of bias. We have presented the findings narratively. We mainly compared ODE with self-directed/face-to-face learning and blended learning with self-directed/face-to-face learning. RESULTS: A total of 93 studies (N=16,895) were included, of which 76 compared ODE (including blended) and self-directed/face-to-face learning. Overall, the effect of ODE (including blended) on postintervention knowledge, skills, attitude, satisfaction, practice or behavior change, and patient outcomes was inconsistent and ranged mostly from no difference between the groups to higher postintervention score in the intervention group (small to large effect size, very low to low quality evidence). Twenty-one studies reported higher knowledge scores (small to large effect size and very low quality) for the intervention, while 20 studies reported no difference in knowledge between the groups. Seven studies reported higher skill score in the intervention (large effect size and low quality), while 13 studies reported no difference in the skill scores between the groups. One study reported a higher attitude score for the intervention (very low quality), while four studies reported no difference in the attitude score between the groups. Four studies reported higher postintervention physician satisfaction with the intervention (large effect size and low quality), while six studies reported no difference in satisfaction between the groups. Eight studies reported higher postintervention practice or behavior change for the ODE group (small to moderate effect size and low quality), while five studies reported no difference in practice or behavior change between the groups. One study reported higher improvement in patient outcome, while three others reported no difference in patient outcome between the groups. None of the included studies reported any unintended/adverse effects or cost-effectiveness of the interventions. CONCLUSIONS: Empiric evidence showed that ODE and blended learning may be equivalent to self-directed/face-to-face learning for training practicing physicians. Few other studies demonstrated that ODE and blended learning may significantly improve learning outcomes compared to self-directed/face-to-face learning. The quality of the evidence in these studies was found to be very low for knowledge. Further high-quality randomized controlled trials are required to confirm these findings.
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Educação a Distância/métodos , Educação Médica/métodos , Médicos/normas , Humanos , AprendizagemRESUMO
Gourgoulis, V, Valkoumas, I, Boli, A, Aggeloussis, N, and Antoniou, P. Effect of an 11-week in-water training program with increased resistance on the swimming performance and the basic kinematic characteristics of the front crawl stroke. J Strength Cond Res 33(1): 95-103, 2019-The purpose of the study was to assess the effect of an 11-week in-water training program with increased resistance on the swimming performance and the basic kinematic characteristics of the front crawl stroke in young female swimmers. Twelve swimmers were matched in pairs according to their best performance in 50-m front crawl swimming and then were randomly assigned to an experimental or to a control group. Both groups followed exactly the same swimming training program. The only exception was that the experimental group performed a sprint training section with increased resistance pulling a water parachute, whereas the control group performed the same section without parachute. Before and after the intervention program, the best performance of both groups in 50-, 100-, and 200-m front crawl swimming were assessed. Moreover, the basic kinematic characteristics of the stroke were calculated during 50-m front crawl swimming with maximal intensity. Two-way repeated measures analyses of variance revealed significant improvement in the best performance in all swimming distances only in the experimental group (3.22-7.26%). As far as the basic kinematic characteristics of the stroke are concerned, significant modifications were found only in the mean swimming velocity in the experimental group (2.18%), whereas no significant changes were observed in the stroke length, the stroke rate, and the duration of the propulsive, and nonpropulsive phases in both groups. Thus, the findings of the current study revealed a positive effect of the in-water resistance training program in the swimming performance of young female swimmers of moderate performance level, without any negative influence in the basic kinematic characteristics of the stroke.
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Desempenho Atlético/fisiologia , Treinamento Resistido , Natação/fisiologia , Adolescente , Fenômenos Biomecânicos , Feminino , Humanos , ÁguaRESUMO
BACKGROUND: Virtual patients are interactive computer simulations that are increasingly used as learning activities in modern health care education, especially in teaching clinical decision making. A key challenge is how to retrieve and repurpose virtual patients as unique types of educational resources between different platforms because of the lack of standardized content-retrieving and repurposing mechanisms. Semantic Web technologies provide the capability, through structured information, for easy retrieval, reuse, repurposing, and exchange of virtual patients between different systems. OBJECTIVE: An attempt to address this challenge has been made through the mEducator Best Practice Network, which provisioned frameworks for the discovery, retrieval, sharing, and reuse of medical educational resources. We have extended the OpenLabyrinth virtual patient authoring and deployment platform to facilitate the repurposing and retrieval of existing virtual patient material. METHODS: A standalone Web distribution and Web interface, which contains an extension for the OpenLabyrinth virtual patient authoring system, was implemented. This extension was designed to semantically annotate virtual patients to facilitate intelligent searches, complex queries, and easy exchange between institutions. The OpenLabyrinth extension enables OpenLabyrinth authors to integrate and share virtual patient case metadata within the mEducator3.0 network. Evaluation included 3 successive steps: (1) expert reviews; (2) evaluation of the ability of health care professionals and medical students to create, share, and exchange virtual patients through specific scenarios in extended OpenLabyrinth (OLabX); and (3) evaluation of the repurposed learning objects that emerged from the procedure. RESULTS: We evaluated 30 repurposed virtual patient cases. The evaluation, with a total of 98 participants, demonstrated the system's main strength: the core repurposing capacity. The extensive metadata schema presentation facilitated user exploration and filtering of resources. Usability weaknesses were primarily related to standard computer applications' ease of use provisions. Most evaluators provided positive feedback regarding educational experiences on both content and system usability. Evaluation results replicated across several independent evaluation events. CONCLUSIONS: The OpenLabyrinth extension, as part of the semantic mEducator3.0 approach, is a virtual patient sharing approach that builds on a collection of Semantic Web services and federates existing sources of clinical and educational data. It is an effective sharing tool for virtual patients and has been merged into the next version of the app (OpenLabyrinth 3.3). Such tool extensions may enhance the medical education arsenal with capacities of creating simulation/game-based learning episodes, massive open online courses, curricular transformations, and a future robust infrastructure for enabling mobile learning.
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Simulação por Computador , Educação Médica/métodos , Internet , Simulação de Paciente , Interface Usuário-Computador , Pessoal de Saúde , Humanos , Projetos Piloto , Semântica , Software , Estudantes de MedicinaRESUMO
The aim of this study was to assess the effect of the hand's acceleration on the propulsive forces and the relative contribution of the drag and lift on their resultant force in the separate phases of the front crawl underwater arm stroke. Ten female swimmers swam one trial of all-out 25-m front crawl. The underwater motion of each swimmer's right hand was recorded using four camcorders and four periscope systems. Anatomical landmarks were digitised, and the propulsive forces generated by the swimmer's hand were estimated from the kinematic data in conjunction with hydrodynamic coefficients. When the hand's acceleration was taken into account, the magnitude of the propulsive forces was greater, with the exception of the mean drag force during the final part of the underwater arm stroke. The mean drag force was greater than the mean lift force in the middle part, while the mean lift force was greater than the mean drag force in the final part of the underwater arm stroke. Thus, swimmers should accelerate their hands from the beginning of their backward motion, press the water with large pitch angles during the middle part and sweep with small pitch angles during the final part of their underwater arm stroke.
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Mãos/fisiologia , Natação/fisiologia , Aceleração , Adolescente , Fenômenos Biomecânicos , Feminino , Humanos , Movimento , Estudos de Tempo e Movimento , Adulto JovemRESUMO
BACKGROUND: Since their inception, virtual patients have provided health care educators with a way to engage learners in an experience simulating the clinician's environment without danger to learners and patients. This has led this learning modality to be accepted as an essential component of medical education. With the advent of the visually and audio-rich 3-dimensional multi-user virtual environment (MUVE), a new deployment platform has emerged for educational content. Immersive, highly interactive, multimedia-rich, MUVEs that seamlessly foster collaboration provide a new hotbed for the deployment of medical education content. OBJECTIVE: This work aims to assess the suitability of the Second Life MUVE as a virtual patient deployment platform for undergraduate dental education, and to explore the requirements and specifications needed to meaningfully repurpose Web-based virtual patients in MUVEs. METHODS: Through the scripting capabilities and available art assets in Second Life, we repurposed an existing Web-based periodontology virtual patient into Second Life. Through a series of point-and-click interactions and multiple-choice queries, the user experienced a specific periodontology case and was asked to provide the optimal responses for each of the challenges of the case. A focus group of 9 undergraduate dentistry students experienced both the Web-based and the Second Life version of this virtual patient. The group convened 3 times and discussed relevant issues such as the group's computer literacy, the assessment of Second Life as a virtual patient deployment platform, and compared the Web-based and MUVE-deployed virtual patients. RESULTS: A comparison between the Web-based and the Second Life virtual patient revealed the inherent advantages of the more experiential and immersive Second Life virtual environment. However, several challenges for the successful repurposing of virtual patients from the Web to the MUVE were identified. The identified challenges for repurposing of Web virtual patients to the MUVE platform from the focus group study were (1) increased case complexity to facilitate the user's gaming preconception in a MUVE, (2) necessity to decrease textual narration and provide the pertinent information in a more immersive sensory way, and (3) requirement to allow the user to actuate the solutions of problems instead of describing them through narration. CONCLUSIONS: For a successful systematic repurposing effort of virtual patients to MUVEs such as Second Life, the best practices of experiential and immersive game design should be organically incorporated in the repurposing workflow (automated or not). These findings are pivotal in an era in which open educational content is transferred to and shared among users, learners, and educators of various open repositories/environments.
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Simulação por Computador , Instrução por Computador/métodos , Educação em Odontologia/métodos , Internet , Simulação de Paciente , Interface Usuário-Computador , Grupos Focais , Humanos , Aprendizagem Baseada em Problemas , Jogos de VídeoRESUMO
The aim of this study was to examine the influence of leg kick on the pattern, the orientation and the propulsive forces produced by the hand, the efficiency of the arm stroke, the trunk inclination, the inter-arm coordination and the intra-cyclic horizontal velocity variation of the hip in sprint front crawl swimming. Nine female swimmers swam two maximal trials of 25 m front crawl, with and without leg kick. Four camcorders were used to record the underwater movements. Using the legs, the mean swimming velocity increased significantly. On the contrary, the velocity and the orientation of the hand, the magnitude and the direction of the propulsive forces, as well as the Froude efficiency of the arm stroke were not modified. The hip intra-cyclic horizontal velocity variation was also not changed, while the index of coordination decreased significantly. A significant decrease (13%) was also observed in the inclination of the trunk. Thus, the positive effect of leg kick on the swimming speed, besides the obvious direct generation of propulsive forces from the legs, could probably be attributed to the reduction of the body's inclination, while the generation of the propulsive forces and the efficiency of the arm stroke seem not to be significantly affected.
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Perna (Membro) , Movimento , Postura , Natação , Análise e Desempenho de Tarefas , Adolescente , Adulto , Braço , Fenômenos Biomecânicos , Feminino , Mãos , Quadril , Humanos , Gravação em Vídeo , Adulto JovemRESUMO
Physical activity and sports can be considered important sources of motivation for people with visual impairments; however limited attention has been given to blind peoples' involvement in sports and to the intra-personal variables such as self-esteem and motivation that affect their sport participation. The purpose of the present study was a) to explore the relationship between self-esteem and intrinsic motivation in blind athletes, and b) to assess the levels of self-esteem and intrinsic motivation and identify differences in intrinsic motivation and self-esteem as a function of gender and sport type (individual-team sports). Participants were 78 (27 females) Greek blind athletes (30.29 ± 1.18 years of age) competing in team (N = 44) and individual (N = 34) sports. Participants completed the Intrinsic Motivation Inventory questionnaire (IMI) and Rosenberg Self-Esteem Scale (RSES) questionnaire. The findings revealed that high values on self-esteem could predict blind athletes' perceived competence (p = .001) and strengthen their intrinsic motivation while enabling them to regulate pressure and tension (p < .05). However, female athletes appeared to be more pressured than males (p < .05), and interestingly, team sport athletes scored higher in intrinsic motivation than individual sports athletes (p < .05). The findings provide useful insights regarding the role of self-esteem in blind athletes' motivational profiles and draw attention to the role of perceived competence in blind athletes' sporting experiences, emphasizing that team sport context may serve as a fertile ground for enhancing intrinsic motivation.
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Atletas , Motivação , Autoimagem , Humanos , Feminino , Masculino , Adulto , Grécia , Atletas/psicologia , Cegueira/psicologia , Inquéritos e Questionários , Esportes/psicologia , Fatores Sexuais , Adulto Jovem , Esportes de EquipeRESUMO
Introduction: The expansive curricular volume of healthcare education makes a necessity the incorporation of innovative methods and immersive media in it. The core challenge in such approaches is the timely development of relevant immersive content such as Virtual, Augmented or Mixed Reality (VR/AR/MR) resources for healthcare topics. There is currently significant interest in the use of co-creative methods for streamlining immersive content development. Methods: A core research pursuit in this translational research field is the formulation of evidence-based, optimized workflows that streamline immersive content creation allowing for rapid expansion of innovative educational approaches in healthcare curricula. The purpose of this paper is to aggregate the perceptions of healthcare technologists and educators who participated in a series of co-creation sessions in order to elicit their best practice insights for design and development of XR educational resources using co-creative methods. Results: According to our thematic analysis, findings of the qualitative study demonstrated that a rigorous organizational approach is required to maintain a constructive exchange of information and to keep the design process alive for both content and technical experts. In addition, rapid prototype and display of co-created features can empower their contributions and help them design more efficiently. Discussion: Co-creative content production can benefit from adaption of existing frameworks and lightweight authoring environments that can facilitate generalized XR content development use cases.
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BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a leading cause of mortality and morbidity. Patient knowledge about AF and its management is paramount but often limited. Patients need to be appropriately informed about treatment options, medicinal adherence, and potential consequences of nonadherence, while also understanding treatment goals and expectations from it. Mobile health apps have experienced an explosion both in their availability and acceptance as "soft interventions" for patient engagement and education; however, the prolific nature of such solutions revealed a gap in the evidence base regarding their efficacy and impact. Virtual patients (VPs), interactive computer simulations, have been used as learning activities in modern health care education. VPs demonstrably improved cognitive and behavioral skills; hence, they have been effectively implemented across undergraduate and postgraduate curricula. However, their application in patient education has been rather limited so far. OBJECTIVE: This work aims to implement and evaluate the efficacy of a mobile-deployed VP regimen for the education and engagement of patients with AF on crucial topics regarding their condition. A mobile VP app is being developed with the goal of each VP being a simple scenario with a set goal and very specific messages and will be subsequently attempted and evaluated. METHODS: A mobile VP player app is being developed so as to be used for the design of 3 educational scenarios for AF management. A pseudorandomized controlled trial for the efficacy of VPs is planned to be executed at 3 sites in Greece, Ukraine, and Kazakhstan for patients with AF. The Welch t test will be used to demonstrate the performance of patients' evaluation of the VP experience. RESULTS: Our study is at the development stage. A preliminary study regarding the system's development and feasibility was initiated in December 2022. The results of our study are expected to be available in 2024 or when the needed sample size is achieved. CONCLUSIONS: This study aims to evaluate and demonstrate the first significant evidence for the value of VP resources in outreach and training endeavors for empowering and patients with AF and fostering healthy habits among them. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45946.
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The purpose of the current study was to investigate the acute effect of sprint resisted front crawl swimming on the propulsive forces of the hand. Eight female swimmers swam 25 m with maximal intensity, with and without added resistance. A bowl with a capacity of 2.2, 4 and 6 L was used as low, moderate and high added resistance, respectively. The underwater motion of the swimmer's right hand was recorded using 4 cameras (60 Hz) and the digitization was undertaken using the Ariel Performance Analysis System. Repeated-measures ANOVA revealed that the velocity of the hand, the pitch and the sweepback angles of the hand, as well as the magnitude and the relative contribution of the drag and lift forces were not significantly modified and thus the magnitude of the resultant force did not change. Moreover, the magnitude of the effective force, as well as the angle formed between the resultant force and the axis of the swimming propulsion were not significantly affected. Thus, it could be concluded that resistance added as in this study did not alter the pattern of the propulsive hand forces associated with front crawl sprinting.
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Desempenho Atlético/fisiologia , Mãos/fisiologia , Modelos Biológicos , Esforço Físico/fisiologia , Postura/fisiologia , Treinamento Resistido/métodos , Adolescente , Simulação por Computador , Feminino , Fricção/fisiologia , Humanos , Estresse MecânicoRESUMO
The purpose was to assess the effect of an 11-week resisted swim training program using a water parachute on the inter-arm coordination in front crawl swimming. Fourteen female swimmers were divided into a control and an experimental group, and followed the same training program, except for the use of a water parachute by the experimental group in specific sprint sets. Before and after the intervention, the underwater motion of the swimmers was recorded using four camcorders and the digitisation process was undertaken manually. The two-way repeated measures analyses of variance revealed a significant increase of the swimming velocity, due to a significant increased stroke rate, because of the significant reduction of the total stroke duration, only in the experimental group. Moreover, their absolute and relative duration of the propulsive pull and push phases increased significantly, while the absolute and relative duration of their non-propulsive entry & catch and recovery phases decreased significantly. These modifications caused a significant increase in the index of coordination. Thus, this 11-week sprint resisted intervention program seems to improve the propulsion continuity and could be considered as an effective form of training, increasing the stroke rate and consequently the swimming velocity.
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Natação , Água , Humanos , Feminino , Fenômenos Biomecânicos , Movimento (Física)RESUMO
Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the ß-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding of these mechanisms and their outcome in gene expression has paved the way to the development of new therapeutic strategies for treating various diseases, such as ß-hemoglobinopathies. Histone deacetylase and DNA methyl-transferase inhibitors are currently being tested in clinical trials for hemoglobinopathies patients. However, these approaches are often uncertain, non-specific and their global effect poses serious safety concerns. Epigenome editing is a recently developed and promising tool that consists of a DNA recognition domain (zinc finger, transcription activator-like effector or dead clustered regularly interspaced short palindromic repeats Cas9) fused to the catalytic domain of a chromatin-modifying enzyme. It offers a more specific targeting of disease-related genes (e.g., the ability to reactivate the fetal γ-globin genes and improve the hemoglobinopathy phenotype) and it facilitates the development of scarless gene therapy approaches. Here, we summarize the mechanisms of epigenome regulation of the ß-globin locus, and we discuss the application of epigenome editing for the treatment of hemoglobinopathies.
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Epigênese Genética , Hemoglobinopatias , Humanos , Epigênese Genética/genética , Epigenoma , Hemoglobinopatias/genética , Hemoglobinopatias/terapia , Globinas beta/genética , Globinas beta/metabolismo , Cromatina , DNA/metabolismoRESUMO
Virtual reality (VR) technologies have rapidly developed in the past few years. The most common application of the technology, apart from gaming, is for educational purposes. In the field of healthcare, VR technologies have been applied in several areas. Among them is surgical education. With the use of VR, surgical pathways along with the training of surgical skills can be explored safely, in a cost-effective manner. The aim of this mini-review was to explore the use of VR in surgical education and in the 3D reconstruction of internal organs and viable surgical pathways. Finally, based on the outcomes of the included studies, an ecosystem for the implementation of surgical training was proposed.
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ENTICE aimed to use co-creative methodologies in order to build a solid creation pipeline for medical experiential content. The project has developed and evaluated immersive learning resources and tools aiming to support well-defined learning objectives using tangible and intangible resources (AR/VR/MR, 3D printing) that are highly sought in the fields of anatomy and surgery. In this paper the preliminary results from the evaluation of the learning resources and tools in 3 countries as well as the lessons learnt are presented towards to the improvement of the medical education process.
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Educação Médica , Realidade Virtual , Aprendizagem , Terapia Comportamental , Impressão TridimensionalRESUMO
Considerable attention nowadays has been given to collaborative learning as a powerful way of learning, however, the ability to provide student-centered learning, meet student needs and provide them with the opportunity to learn, is a challenging task and has received significant research attention. CLUEDUP proposes an innovative educational protocol that integrates game-based learning with pedagogical approaches that matches students' needs and skills and promotes collaborative interactive and decision-based learning.