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1.
Sensors (Basel) ; 22(12)2022 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-35746232

RESUMEN

In this research, a heartbeat classification method is presented based on evolutionary feature optimization using differential evolution (DE) and classification using a probabilistic neural network (PNN) to discriminate between normal and arrhythmic heartbeats. The proposed method follows four steps: (1) preprocessing, (2) heartbeat segmentation, (3) DE feature optimization, and (4) PNN classification. In this method, we have employed direct signal amplitude points constituting the heartbeat acquired from the ECG holter device with no secondary feature extraction step usually used in case of hand-crafted, frequency transformation or other features. The heartbeat types include normal, left bundle branch block, right bundle branch block, premature ventricular contraction, atrial premature, ventricular escape, ventricular flutter and paced beat. Using ECG records from the MIT-BIH, heartbeats are identified to start at 250 ms before and end at 450 ms after the respective R-peak positions. In the next step, the DE method is applied to reduce and optimize the direct heartbeat features. Although complex and highly computational ECG heartbeat classification algorithms have been proposed in the literature, they failed to achieve high performance in detecting some minority heartbeat categories, especially for imbalanced datasets. To overcome this challenge, we propose an optimization step for the deep CNN model using a novel classification metric called the Matthews correlation coefficient (MCC). This function focuses on arrhythmia (minority) heartbeat classes by increasing their importance. Maximum MCC is used as a fitness function to identify the optimum combination of features for the uncorrelated and non-uniformly distributed eight beat class samples. The proposed DE-PNN scheme can provide better classification accuracy considering 8 classes with only 36 features optimized from a 253 element feature set implying an 85.77% reduction in direct amplitude features. Our proposed method achieved overall 99.33% accuracy, 94.56% F1, 93.84% sensitivity, and 99.21% specificity.


Asunto(s)
Electrocardiografía , Procesamiento de Señales Asistido por Computador , Algoritmos , Arritmias Cardíacas/diagnóstico , Electrocardiografía/métodos , Frecuencia Cardíaca , Humanos , Redes Neurales de la Computación
2.
Sensors (Basel) ; 22(2)2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35062465

RESUMEN

This paper reported a study on the 3-dimensional deep-learning-based automatic diagnosis of nasal fractures. (1) Background: The nasal bone is the most protuberant feature of the face; therefore, it is highly vulnerable to facial trauma and its fractures are known as the most common facial fractures worldwide. In addition, its adhesion causes rapid deformation, so a clear diagnosis is needed early after fracture onset. (2) Methods: The collected computed tomography images were reconstructed to isotropic voxel data including the whole region of the nasal bone, which are represented in a fixed cubic volume. The configured 3-dimensional input data were then automatically classified by the deep learning of residual neural networks (3D-ResNet34 and ResNet50) with the spatial context information using a single network, whose performance was evaluated by 5-fold cross-validation. (3) Results: The classification of nasal fractures with simple 3D-ResNet34 and ResNet50 networks achieved areas under the receiver operating characteristic curve of 94.5% and 93.4% for binary classification, respectively, both indicating unprecedented high performance in the task. (4) Conclusions: In this paper, it is presented the possibility of automatic nasal bone fracture diagnosis using a 3-dimensional Resnet-based single classification network and it will improve the diagnostic environment with future research.


Asunto(s)
Aprendizaje Profundo , Fracturas Óseas , Humanos , Redes Neurales de la Computación , Curva ROC , Tomografía Computarizada por Rayos X
3.
Gene Ther ; 27(12): 545-556, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32341484

RESUMEN

Autologous gene therapy using lentiviral vectors (LVs) holds promise for treating monogenetic blood diseases. However, clinical applications can be limited by suboptimal hematopoietic stem cell (HSC) transduction and insufficient quantities of available vector. We recently reported gene therapy for X-linked severe combined immunodeficiency using a protocol in which patient CD34+ cells were incubated with two successive transductions. Here we describe an improved protocol for LV delivery to CD34+ cells that simplifies product manipulation, reduces vector consumption, and achieves greater vector copy number (VCN) of repopulating HSCs in mouse xenotransplantation assays. Notable findings include the following: (1) the VCN of CD34+ cells measured shortly after transduction did not always correlate with the VCN of repopulating HSCs after xenotransplantation; (2) single-step transduction at higher CD34+ cell concentrations (2-4 × 106/ml) conserved LV without compromising HSC VCN; (3) poloxamer F108 (LentiBOOST) increased HSC VCN by two- to threefold (average from three donors); (4) although LentiBOOST + prostaglandin E2 combination further increased VCN in vitro, the VCN observed in vivo were similar to LentiBOOST alone; (5) cyclosporine H increased the HSC VCN to a similar or greater extent with LentiBOOST in vivo. Our findings delineate an improved protocol to increase the VCN of HSCs after CD34+ cell transduction with clinically relevant LVs.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Lentivirus , Animales , Antígenos CD34 , Terapia Genética , Vectores Genéticos/genética , Células Madre Hematopoyéticas , Humanos , Lentivirus/genética , Ratones , Transducción Genética
4.
Knee Surg Sports Traumatol Arthrosc ; 28(8): 2626-2633, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32062684

RESUMEN

PURPOSE: The purpose of the study was to determine the change in the graft bending angles at the femoral and tibial tunnel aperture in single-bundle posterior cruciate ligament (PCL) reconstruction. It was hypothesized that different knee flexion and different tunnel directions may affect changes of the femoral and tibial graft bending angle. METHODS: The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at 4 different knee flexion angles (0°, 45°, 90° and 135°). To begin with, the 3D knee models were created and manipulated with the use of several modeling programs. Single-bundle PCL reconstruction was then virtually conducted in a 90° flexion model: The femoral and tibial graft bending angle, according to the various knee flexion angles, was calculated using a special software program. RESULTS: The femoral graft bending angle significantly decreased as the knee flexion increased between 0° and 135° (all p < 0.001). The femoral graft bending angle of the AL graft showed the most obtuse angles among the three types of the graft beyond 45° of knee flexion. For the tibial graft bending angle, the anteromedial tunnel group showed significantly more acute tibial graft bending angle than the anterolateral tunnel group in all three types of the graft at all flexion angles (all p < 0.001). CONCLUSION: Changes in the femoral graft bending angle were generally affected by different knee flexion angles. The effect of tibial tunnel direction on the tibial graft bending angle was found to be significant. The clinical relevance is that a mostly obtuse femoral graft bending angle was shown by the AL graft among three types of the graft.


Asunto(s)
Articulación de la Rodilla/fisiología , Reconstrucción del Ligamento Cruzado Posterior/métodos , Ligamento Cruzado Posterior/fisiología , Ligamento Cruzado Posterior/cirugía , Trasplantes/fisiología , Adulto , Fémur/cirugía , Humanos , Imagenología Tridimensional , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Ligamento Cruzado Posterior/diagnóstico por imagen , Ligamento Cruzado Posterior/lesiones , Rango del Movimiento Articular , Tibia/cirugía , Tomografía Computarizada por Rayos X , Trasplantes/diagnóstico por imagen
5.
Arthroscopy ; 35(1): 14-21, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30455087

RESUMEN

PURPOSE: To introduce an arthroscopically assisted coracoclavicular (CC) fixation technique using multiple low-profile devices to evaluate the clinical and radiologic outcomes in patients with acute high-grade acromioclavicular (AC) joint dislocation. METHODS: Between July 2014 and September 2015, cases of AC joint dislocation that were treated with arthroscopic CC fixation using multiple low-profile devices with a minimum follow-up of 24 months were included. We measured the vertical coracoclavicular distance (CCD) on the anteroposterior view and the horizontal acromioclavicular distance on 3-dimensional computed tomography images to evaluate the changes in radiologic outcomes before and after surgery. We compared final radiologic outcomes between initial AC reduction groups based on hierarchical clustering. Clinical outcomes were evaluated using the Constant-Murley score. RESULTS: We enrolled 27 patients in total, and the mean follow-up period was 27.2 months. The mean CCD of the injured shoulder was 13.68 ± 3.98 mm preoperatively and decreased to 5.72 ± 1.68 mm immediately postoperatively but increased to 7.32 ± 2.29 mm at last follow-up (P = .07). Horizontal displacement of the distal clavicle was 1.1 ± 1.0 mm immediately postoperatively but decreased to 0.9 ± 0.6 mm at last follow-up (P < .05). In particular, in the 2 groups that were determined using the hierarchical cluster analysis, patients with excellent recovery of the initial CCD (20 patients) showed less of an increase in the CCD at last follow-up than did those in the other group (7 patients) (P < .001). The Constant-Murley score was 93.5 ± 2.7 points on the injured side at last follow-up (P = .074). CONCLUSIONS: Our CC fixation technique with multiple low-profile devices exhibited satisfactory clinical and radiologic outcomes. In particular, ensuring good initial recovery of the CCD and the precise placement and location of the AC joints was important in maintaining the proper AC position at the final follow-up. LEVEL OF EVIDENCE: Level IV, case series.


Asunto(s)
Articulación Acromioclavicular/cirugía , Artroscopía/métodos , Luxaciones Articulares/cirugía , Articulación Acromioclavicular/diagnóstico por imagen , Adulto , Clavícula/cirugía , Apófisis Coracoides/cirugía , Femenino , Estudios de Seguimiento , Humanos , Imagenología Tridimensional , Luxaciones Articulares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Anclas para Sutura , Suturas , Tomografía Computarizada por Rayos X , Adulto Joven
6.
J Orthop Sci ; 24(1): 87-94, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30268356

RESUMEN

BACKGROUND: This study aimed to investigate impingement-free range of motion (ROM) of the glenohumeral joint following reverse total shoulder arthroplasty (RTSA) with three types of implant models using computational motion analysis. METHODS: Three-dimensional (3D) scapulohumeral models were created from preoperative computed tomography (CT) images of seven patients by using visualization and computer-aided design software. Three types of implant designs, namely, typical medialization, in between, and lateralization implants, were used for the reconstruction of 3D model; each design was designated as group I, II, and III, respectively. All possible combinations of virtual surgeries were evaluated for impingement-free ROM in all three groups. Maximal ROMs were compared. The effect of implant positions on ROM of the shoulder joints were investigated in each group. RESULTS: The all lateralization group (group III) showed significantly greatest maximal adduction, abduction and external rotation (ER). Adduction and abduction were significantly increased by the glenoid component inferior translation in all three groups. (In group I, p < 0.001 for adduction, p = 0.002 for abduction, respectively; in group II, p = 0.025, p < 0.001, respectively; in group III, p = 0.038, p = 0.011, respectively). Increasing humerus retroversion might have some effect on increasing abduction. In group II and III, internal rotation (IR) and ER were significantly affected by the humerus retroversion (in group II, p = 0.033 for IR, p = 0.007 for ER, respectively; in group III, p = 0.004, p < 0.001, respectively). In group III, ER was also significantly affected by the glenoid component inferior translation (p = 0.003). CONCLUSIONS: Lateralization design model showed greatest ROM of the shoulder joint. The effects of implant positions on impingement-free ROM exhibited different tendencies between medialization and lateralization implant models. Humerus retroversion affected both IR and ER, especially in lateralization design. Increasing glenoid inferior translation increases both adduction and abduction regardless of implant designs.


Asunto(s)
Artroplastía de Reemplazo de Hombro/métodos , Húmero/diagnóstico por imagen , Imagenología Tridimensional , Escápula/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Humanos , Húmero/cirugía , Diseño de Prótesis , Rango del Movimiento Articular , Estudios Retrospectivos , Escápula/cirugía , Síndrome de Abducción Dolorosa del Hombro/fisiopatología , Articulación del Hombro/fisiopatología , Articulación del Hombro/cirugía
7.
Mol Ther ; 25(3): 593-605, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28190779

RESUMEN

Recently, an engineered Homeobox-nucleoporin fusion gene, NUP98-HOXA10HD or NA10HD, was reported to expand and maintain murine hematopoietic stem cells (HSCs). We postulated that NA10HD would increase the number of human γ-globin-expressing cells to therapeutic levels. We developed a double gene lentiviral vector encoding both human γ-globin and NA10HD, which was used to transduce human peripheral blood CD34+ cells and increased engraftment 2- to 2.5-fold at 15 weeks post-transplantation in immunodeficient mice. In ß-thalassemic mice transplanted with ß-thalassemic HSCs transduced with the γ-globin/NA10HD vector, the number of fetal hemoglobin (HbF)-expressing cells was significantly increased after 3 months, leading to resolution of the anemia. Furthermore, the increases in HbF were maintained at 6 months and persisted after secondary transplantation. In addition, NA10HD enrichment of transduced HSCs led to HbF increases without affecting homeostasis of the white blood cell lineages. Our results suggest that NA10HD increases the number of γ-globin-transduced HSCs that engraft, leading to an elevated number of fetal hemoglobin-containing red cells. These effects of NA10HD provide an improved platform for testing of the therapeutic efficacy of novel globin vectors and provide further impetus to develop safe and effective methods for selective expansion of genetically modified cells.


Asunto(s)
Vectores Genéticos/genética , Células Madre Hematopoyéticas/metabolismo , Proteínas de Homeodominio/genética , Lentivirus/genética , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Talasemia beta/genética , gamma-Globinas/genética , Animales , Modelos Animales de Enfermedad , Eritrocitos/citología , Eritrocitos/metabolismo , Hemoglobina Fetal/metabolismo , Orden Génico , Técnicas de Transferencia de Gen , Sitios Genéticos , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas , Proteínas Homeobox A10 , Humanos , Ratones , Transducción Genética , Trasplante Heterólogo , Talasemia beta/metabolismo , Talasemia beta/terapia
8.
J Phys Ther Sci ; 28(2): 626-31, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27065554

RESUMEN

[Purpose] Currently, various simulators are produced and used for athlete's exercise, rehabilitation, and training. In this study, we analyzed the kinematic factors of sectional and total movements in healthy participants by providing group-dependent information during simulated exercise. [Subjects and Methods] Participants in this study included 26 male adults (non-experts and experts); experts held a certificate issued by the Korea Ski Instructors Association. The elapsed times in each phase, the difference in the lower extremity angles, and muscle activity were computed through analysis of kinematic factors. [Results] We observed that motions in the experts took shorter time to perform than that in non-experts, and showed larger variation of lower limb joint angle in most events during simulated skiing. There were also significant group-dependent differences in the peak and mean EMG values during simulated skiing. [Conclusion] A non-expert's posture leads to enhanced muscle activity to keep the lower body in balance. We suggest the following training guideline: initially, non-experts should maintain appropriate range of motion with lower-intensity exercise to improve muscle endurance. It can be useful in providing preliminary data for future training and rehabilitation studies, as well as improvements in muscle strength and balance.

9.
J Phys Ther Sci ; 28(2): 641-5, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27065556

RESUMEN

[Purpose] Efficient management using exercise programs with various benefits should be provided by educational institutions for children in their growth phase. We analyzed the heart rates of children during ski simulator exercise and the Harvard step test to evaluate the cardiopulmonary endurance by calculating their post-exercise recovery rate. [Subjects and Methods] The subjects (n = 77) were categorized into a normal weight and an overweight/obesity group by body mass index. They performed each exercise for 3 minutes. The cardiorespiratory endurance was calculated using the Physical Efficiency Index formula. [Results] The ski simulator and Harvard step test showed that there was a significant difference in the heart rates of the 2 body mass index-based groups at each minute. The normal weight and the ski-simulator group had higher Physical Efficiency Index levels. [Conclusion] This study showed that a simulator exercise can produce a cumulative load even when performed at low intensity, and can be effectively utilized as exercise equipment since it resulted in higher Physical Efficiency Index levels than the Harvard step test. If schools can increase sport durability by stimulating students' interests, the ski simulator exercise can be used in programs designed to improve and strengthen students' physical fitness.

10.
J Shoulder Elbow Surg ; 24(7): 1106-11, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25618464

RESUMEN

BACKGROUND: The clavicle hook plate can be used to treat acromioclavicular and coracoclavicular ligament injury or distal clavicular fracture with comminution. However, the hook plate can induce subacromial impingement, resulting in discomfort from the hardware. METHODS: Our inclusion criteria were (1) men and women aged older than 20 years and (2) the presence of comminuted distal clavicular fractures (Neer type IIB) fixed with a hook plate (Synthes, Oberdorf, Switzerland). Three-dimensional computed tomography was obtained before removal of the hook plate. Seven patients were enrolled prospectively. The mean age was 42 years (range, 24-60 years). Zero degree images and abduction images were obtained. The sagittal cut surface was obtained 5 mm medial from the distal clavicle. The equator of the cut surface of the clavicle was compared with the full abduction model to analyze rotation. The center of the cut surface of the clavicle was compared with the full abduction model to analyze translation. RESULTS: The average difference in rotation of the distal clavicle between both shoulders was 16° (range, 3°-22°; P = .001). The mean difference in anterior translation of the distal clavicle was 2.2 mm (range, -0.7 to 5.6 mm; P = .030). CONCLUSION: Hook plate fixation at the acromioclavicular joint causes decreased internal rotation and increased anterior translation of the distal clavicle with respect to the medial acromion, indicating that the scapula relative to the thorax has decreased posterior tilting and increased external rotation in shoulders fixed using a hook plate.


Asunto(s)
Articulación Acromioclavicular/diagnóstico por imagen , Clavícula/cirugía , Fracturas Óseas/cirugía , Fracturas Conminutas/cirugía , Articulación Acromioclavicular/lesiones , Articulación Acromioclavicular/cirugía , Adulto , Anciano , Placas Óseas , Clavícula/diagnóstico por imagen , Clavícula/lesiones , Femenino , Fijación Interna de Fracturas , Fracturas Óseas/diagnóstico por imagen , Fracturas Conminutas/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Movimiento , Estudios Prospectivos , Tomografía Computarizada por Rayos X/instrumentación , Adulto Joven
11.
Arthroscopy ; 30(6): 739-46, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24725985

RESUMEN

PURPOSE: To investigate changes in femoral tunnel diameter, dimension, and volume after anterior cruciate ligament reconstruction with notchplasty. METHODS: Porcine knee specimens were divided into 2 groups of 10 specimens each. Group A did not receive notchplasty. A 2-mm notchplasty was conducted in group B. Seven-millimeter-diameter femoral tunnels were drilled and a doubled flexor digitorum profundus tendon was inserted and fixed with an EndoButton (Smith & Nephew, Andover, MA) in each knee specimen. Samples were mounted on a materials testing machine. Each group was preloaded at 10 N and subjected to 20 loading cycles (between 0 and 40 N), followed by 1,000 loading cycles in the elastic region (between 10 and 150 N). High-resolution computed tomography with 1.0-mm slices was conducted with all samples before and after testing. A 3-dimensional model was constructed to evaluate the degree of the tunnel change. RESULTS: In group B the mean longest diameter and dimension of the femoral tunnel significantly increased after the test (P = .005 and P = .001, respectively). The volumetric loss of bony structure after the test in group B was significantly greater than that in group A (P = .039). Meanwhile, no significant difference was found before and after the test in terms of tunnel diameter, dimension, and volumetric loss around the tunnel in group A. CONCLUSIONS: The intra-articular orifice of the femoral tunnel was enlarged after the uniaxial cyclic loading test after notchplasty. An enlarged tunnel orifice may lead to a discrepancy between the tunnel and the graft at the tunnel aperture. CLINICAL RELEVANCE: The data may have an implication that suspensory fixation with a notchplasty has a negative effect on the full graft accommodation at the tunnel aperture. Aperture widening may affect graft positioning, leading to subtle changes in graft biomechanics and laxity.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior/métodos , Fémur/cirugía , Osteotomía/métodos , Animales , Ligamento Cruzado Anterior/cirugía , Densidad Ósea , Femenino , Masculino , Factores Sexuales , Porcinos
12.
Knee Surg Sports Traumatol Arthrosc ; 22(9): 2057-63, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23851970

RESUMEN

PURPOSE: The aim of the study was to analyse the change in length and tension of the reconstructed single-bundle posterior cruciate ligament (PCL) with three different femoral tunnels at different knee flexion angles by use of three-dimensional finite element method. METHODS: The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at four different knee flexion angles (0°, 45°, 90° and 135°). Three types of single-bundle PCL reconstruction were then conducted in a 90° flexion model: femoral tunnels were created in anterolateral (AL), central and posteromedial (PM) regions of the footprint. Length versus flexion curves and tension versus flexion curves were generated. RESULTS: Between 0° and 90° of knee flexion, changes in length and tension in the PM grafts were not significant. Whereas the lengths and tension of the AL and central grafts significantly increased in the same flexion range. The length and tension of the PM grafts at 135° of knee flexion were significantly higher than those at 90° of knee flexion, whereas the AL and the central grafts showed only slight length changes beyond 90° of flexion. However, the tension of the AL graft increased significantly beyond 90° of flexion. CONCLUSIONS: Changes in the graft length, and tension were generally affected by different femoral tunnels and knee flexion angles. In groups with the AL and PM single-bundle reconstruction, the graft tension increased beyond 90° of knee flexion when the graft is tensioned at 90° of flexion. These data suggest that final fixation angle at 90° for the AL or PM graft would induce graft overtension in high knee flexion of 135°. Whereas central graft which is fixed in 90° of flexion is desirable in terms of prevention of graft overtension. Because the graft tension within it was relatively constant beyond 90° of flexion.


Asunto(s)
Artroplastia/métodos , Articulación de la Rodilla/cirugía , Ligamento Cruzado Posterior/cirugía , Trasplantes/fisiopatología , Adulto , Fenómenos Biomecánicos , Fémur/cirugía , Análisis de Elementos Finitos , Humanos , Imagenología Tridimensional , Masculino , Ligamento Cruzado Posterior/fisiopatología , Rango del Movimiento Articular , Tomografía Computarizada por Rayos X , Adulto Joven
13.
ScientificWorldJournal ; 2014: 235858, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25538950

RESUMEN

The demand for an accurate and accessible image segmentation to generate 3D models from CT scan data has been increasing as such models are required in many areas of orthopedics. In this paper, to find the optimal image segmentation to create a 3D model of the knee CT data, we compared and validated segmentation algorithms based on both objective comparisons and finite element (FE) analysis. For comparison purposes, we used 1 model reconstructed in accordance with the instructions of a clinical professional and 3 models reconstructed using image processing algorithms (Sobel operator, Laplacian of Gaussian operator, and Canny edge detection). Comparison was performed by inspecting intermodel morphological deviations with the iterative closest point (ICP) algorithm, and FE analysis was performed to examine the effects of the segmentation algorithm on the results of the knee joint movement analysis.


Asunto(s)
Algoritmos , Imagenología Tridimensional/métodos , Articulación de la Rodilla , Modelos Teóricos , Movimiento/fisiología , Tomografía Computarizada por Rayos X , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiología , Masculino
14.
Blood ; 117(10): 2817-26, 2011 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-21156846

RESUMEN

ß-Thalassemia major results from severely reduced or absent expression of the ß-chain of adult hemoglobin (α2ß2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of ß-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34(+) cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with ß-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34(+) cells demonstrated levels of HbF up to 21% per vector copy. For ß-thalassemic CD34(+) cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with ß-globin deficiency.


Asunto(s)
Células Precursoras Eritroides/metabolismo , Hemoglobina Fetal/biosíntesis , Técnicas de Transferencia de Gen , Terapia Genética , Talasemia beta/terapia , gamma-Globinas/genética , Antígenos CD34/metabolismo , Southern Blotting , Western Blotting , Separación Celular , Eritropoyesis/fisiología , Hemoglobina Fetal/genética , Citometría de Flujo , Vectores Genéticos , Humanos , Lentivirus/genética , Reacción en Cadena de la Polimerasa
15.
ACS Appl Mater Interfaces ; 15(21): 26028-26036, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37199761

RESUMEN

Polymer materials are extensively used because of their excellent performance; however, when used for a long time, they break and eventually lose their original properties. Thus, smart polymer materials that can repeatedly detect and repair damage must be urgently developed to increase their durability and lifespan. In this study, a smart material with dual functionality (damage-detection and self-healing) is developed via a facile method of incorporating spiropyran (SP) beads, which exhibit changes in color and fluorescence when damaged, into a Diels-Alder (DA)-based self-healing matrix. When polyurethane (PU) is added to the DA-based matrix, the dual functionality exhibits a strong dependence on the proportion of PU. Because the PU ratio affects two opposing factors (damaged area and load-bearing capacity), the damage-detecting ability exhibits the best performance at 40 wt % PU, where both factors are optimized. A high healing efficiency of 96% is achieved via a dynamic DA reaction. In particular, the repeatability of the dual-functionality is successfully attained through the reversibility of the SP beads and DA networks, where the detection and healing efficiencies are reduced by 15 and 23%, respectively, after 10 cycles. Furthermore, the reprocessed fractured specimens exhibit excellent recyclability.

16.
Blood ; 115(15): 3033-41, 2010 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-20190190

RESUMEN

Fetal hemoglobin (HbF) is a potent genetic modifier of the severity of beta-thalassemia and sickle cell anemia. We used an in vitro culture model of human erythropoiesis in which late-stage erythroblasts are derived directly from human CD34(+) hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes according to the developmental stage of the originating cell source. When cytokine-mobilized peripheral blood CD34(+) cells from adults were cultured, background levels of HbF were 2% or less. Cultured cells were readily transduced with lentiviral vectors when exposed to vector particles between 48 and 72 hours. Among the genetic elements that may enhance fetal hemoglobin production is an artificial zinc-finger transcription factor, GG1-VP64, designed to interact with the proximal gamma-globin gene promoters. Our data show that lentiviral-mediated, enforced expression of GG1-VP64 under the control of relatively weak erythroid-specific promoters induced significant amounts of HbF (up to 20%) in erythroblasts derived from adult CD34(+) cells without altering their capacity for erythroid maturation and only modestly reducing the total numbers of cells that accumulate in culture after transduction. These observations demonstrate the potential for sequence-specific enhancement of HbF in patients with beta-thalassemia or sickle cell anemia.


Asunto(s)
Eritroblastos/metabolismo , Hemoglobina Fetal/biosíntesis , Regiones Promotoras Genéticas/genética , Transactivadores/metabolismo , Dedos de Zinc , gamma-Globinas/genética , Adulto , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cromatina/metabolismo , Citocinas/farmacología , Eritroblastos/citología , Eritroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Vectores Genéticos/genética , Movilización de Célula Madre Hematopoyética , Humanos , Lentivirus/genética , Modelos Genéticos , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/genética , Unión Proteica/efectos de los fármacos , Transducción Genética
17.
Molecules ; 17(5): 5404-11, 2012 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-22569419

RESUMEN

This study investigated the immunostimulatory effects of laminarin with respect to inflammatory mediators such as hydrogen peroxide, calcium, nitric oxide, various cytokines, transcription factors, and immune response gene in RAW 264.7 mouse macrophages. Laminarin did not reduce the cell proliferation of RAW 264.7 mouse macrophages at concentrations up to 500 µg/mL. Laminarin significantly increased the release of hydrogen peroxide, calcium, nitric oxide, monocyte chemotactic protein-1, vascular endothelial growth factor, leukemia inhibitory factor, and granulocyte-colony stimulating factor with enhancing expression of Signal Transducer and Activator of Transcription 1 (STAT1), STAT3, c-Jun, c-Fos, and cyclooxygenase-2 mRNA in RAW 264.7 cells. The results suggest that laminarin has immunostimulatory properties, strengthening immune reactions via the transcription factor pathway in macrophages.


Asunto(s)
Expresión Génica/efectos de los fármacos , Factores Inmunológicos/farmacología , Macrófagos/efectos de los fármacos , Polisacáridos/farmacología , Animales , Calcio/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Expresión Génica/inmunología , Genes fos/genética , Genes fos/inmunología , Genes jun/genética , Genes jun/inmunología , Glucanos , Factor Estimulante de Colonias de Granulocitos/genética , Factor Estimulante de Colonias de Granulocitos/inmunología , Peróxido de Hidrógeno/metabolismo , Factor 3 de Genes Estimulados por el Interferón/genética , Factor 3 de Genes Estimulados por el Interferón/inmunología , Factor Inhibidor de Leucemia/genética , Factor Inhibidor de Leucemia/inmunología , Macrófagos/citología , Macrófagos/inmunología , Ratones , Óxido Nítrico/biosíntesis , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/inmunología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/inmunología
18.
JMIR Serious Games ; 10(3): e36397, 2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36166294

RESUMEN

BACKGROUND: Recently, technology that provides virtual reality (VR) content based on streaming services has been rapidly developed. However, there have been few studies to reduce VR sickness that occurs while the user watches VR content while wearing a head-mounted display (HMD) in real time. OBJECTIVE: Based on this background, we propose a new approach to measure and reduce VR sickness that occurs while the user watches VR content while wearing an HMD in real time. METHODS: The proposed approach is to apply VR sickness reduction methods in accordance with the user's real-time VR sickness level. Three methods that are known to be effective in reducing VR sickness and a single type of VR content were used to examine the effectiveness of the proposed approach, which was confirmed by the experimental results. RESULTS: Our results show that VR sickness significantly decreased when a new approach was applied to VR content (in all cases, P<.05). CONCLUSIONS: From our results, it was confirmed that VR sickness could be measured without wearing additional equipment, and its reduction method could be applied in real time in accordance with the user's condition by the proposed approach in this paper.

19.
JMIR Serious Games ; 10(4): e37938, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36251360

RESUMEN

BACKGROUND: Although more people are experiencing cybersickness due to the popularization of virtual reality (VR), no official standard for the cause and reduction of cybersickness exists to date. One of the main reasons is that an objective method to assess cybersickness has not been established. To resolve this, research on evaluating cybersickness with physiological responses that can be measured in real time is required. Since research on deriving physiological responses that can assess cybersickness is at an early stage, further studies examining various physiological responses are needed. OBJECTIVE: This study analyzed the effects of cybersickness caused by head-mounted display-based VR on physiological responses. METHODS: We developed content that provided users with a first-person view of an aircraft that moved (with translation and combined rotation) over a city via a predetermined trajectory. In the experiment, cybersickness and the physiological responses of participants were measured. Cybersickness was assessed by the Simulator Sickness Questionnaire (SSQ). The measured physiological responses were heart rate, blood pressure, body temperature, and cortisol level. RESULTS: Our measurement confirmed that all SSQ scores increased significantly (all Ps<.05) when participants experienced cybersickness. Heart rate and cortisol level increased significantly (P=.01 and P=.001, respectively). Body temperature also increased, but there was no statistically significant difference (P=.02). Systolic blood pressure and diastolic blood pressure decreased significantly (P=.001). CONCLUSIONS: Based on the results of our analysis, the following conclusions were drawn: (1) cybersickness causes significant disorientation, and research on this topic should focus on factors that affect disorientation; and (2) the physiological responses that are suitable for measuring cybersickness are heart rate and cortisol level.

20.
Yonsei Med J ; 63(7): 657-664, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35748077

RESUMEN

PURPOSE: We aimed to analyze changes in suprascapular nerve (SSN) position within the suprascapular notch during in vivo shoulder abduction. MATERIALS AND METHODS: Three-dimensional models of the shoulder complex were constructed based on magnetic resonance imaging of the brachial plexus (BP-MR) in a patient diagnosed with SSN dysfunction but normal scapular movement. Using BP-MR in neutral position and computed tomography data on shoulder abduction, shoulder abduction was simulated as the transition between two positions of the shoulder complex with overlapping of a neutral and abducted scapula. SSN movement during abduction was evaluated using the finite element method. Contact stress on the SSN was measured in the presence and absence of the transverse scapular ligament (TSL). RESULTS: In the neutral position, the SSN ran almost parallel to the front of the TSL until entering the suprascapular notch and slightly contacted the anterior-inferior border of the TSL. As shoulder abduction progressed, contact stress decreased due to gradual loss of contact with the TSL. In the TSL-free scapula, there was no contact stress on the SSN in the neutral position. Towards the end of shoulder abduction, contact stress increased again as the SSN began to contact the base of the suprascapular notch in both TSL conditions. CONCLUSION: We identified changes in the position of the SSN path within the suprascapular notch during shoulder abduction. The SSN starts in contact with the TSL and moves toward the base of the suprascapular notch with secondary contact. These findings may provide rationale for TSL release in SSN entrapment.


Asunto(s)
Plexo Braquial , Síndromes de Compresión Nerviosa , Plexo Braquial/diagnóstico por imagen , Análisis de Elementos Finitos , Humanos , Síndromes de Compresión Nerviosa/diagnóstico por imagen , Escápula/diagnóstico por imagen , Escápula/inervación , Hombro/diagnóstico por imagen , Hombro/inervación
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