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Demand is strong for sensitive, reliable, and cost-effective diagnostic tools for cancer detection. Accordingly, bead-based biosensors have emerged in recent years as promising diagnostic platforms based on wide-ranging cancer biomarkers owing to the versatility, high sensitivity, and flexibility to perform the multiplexing of beads. This comprehensive review highlights recent trends and innovations in the development of bead-based biosensors for cancer-biomarker detection. We introduce various types of bead-based biosensors such as optical, electrochemical, and magnetic biosensors, along with their respective advantages and limitations. Moreover, the review summarizes the latest advancements, including fabrication techniques, signal-amplification strategies, and integration with microfluidics and nanotechnology. Additionally, the challenges and future perspectives in the field of bead-based biosensors for cancer-biomarker detection are discussed. Understanding these innovations in bead-based biosensors can greatly contribute to improvements in cancer diagnostics, thereby facilitating early detection and personalized treatments.
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Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Humanos , Neoplasias/diagnóstico , Biomarcadores de Tumor/análisis , Técnicas Electroquímicas/métodos , Nanotecnología/tendencias , Nanotecnología/métodos , Nanotecnología/instrumentación , Microfluídica/métodos , Microfluídica/instrumentación , Microfluídica/tendenciasRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity-associated NAFLD and sarcopenia remains unclear. METHODS: ADAR2+/+/GluR-BR/R mice (wild type [WT]) and ADAR2-/-/GluR-BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. RESULTS: ADAR2 KO mice fed with HFD exhibited lower body weight (-7.7%, P < 0.05), lower liver tissue weight (-20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (-24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD-induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD-induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (-37%, P < 0.001), diameter (-20%, P < 0.01), number (-39%, P < 0.001) and fusion index (-46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1-treated myoblast C2C12 cells. CONCLUSIONS: These results provide novel evidence that ADAR2 deficiency may be important in obesity-associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.
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Adenosina Desaminasa , Ratones Noqueados , Atrofia Muscular , Enfermedad del Hígado Graso no Alcohólico , Proteínas de Unión al ARN , Proteína Amiloide A Sérica , Animales , Adenosina Desaminasa/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Atrofia Muscular/metabolismo , Proteína Amiloide A Sérica/metabolismo , Modelos Animales de Enfermedad , Masculino , Dieta Alta en Grasa , Músculo Esquelético/patología , Músculo Esquelético/metabolismoRESUMEN
Background: Due to the Coronavirus disease 19 (COVID-19) related social distancing measures and health service suspension, physical activity has declined, leading to increased falling risk and disability, and consequently, compromising the older adult health. How to improve the quality of older adult life has become a crucial social issue. Objective: In traditional rehabilitation, manual and repetitive muscle training cannot identify the patient's rehabilitation effect, and increasing the willingness to use it is not easy. Therefore, based on the usability perspective, this study aims to develop a novel smart somatosensory wearable assistive device (called SSWAD) combined with wireless surface electromyography (sEMG) and exergame software and hardware technology. The older adult can do knee extension, ankle dorsiflexion, and ankle plantar flexion rehabilitation exercises at home. Meanwhile, sEMG values can be digitally recorded to assist physicians (or professionals) in judgment, treatment, or diagnosis. Methods: To explore whether the novel SSWAD could improve the older adult willingness to use and motivation for home rehabilitation, 25 frail older adult (12 males and 13 females with an average age of 69.3) perform the rehabilitation program with the SSWAD, followed by completing the system usability scale (SUS) questionnaire and the semi-structured interview for the quantitative and qualitative analyses. In addition, we further investigate whether the factor of gender or prior rehabilitation experience would affect the home rehabilitation willingness or not. Results: According to the overall SUS score, the novel SSWAD has good overall usability performance (77.70), meaning that the SSWAD makes older adult feel interested and improves their willingness for continuous rehabilitation at home. In addition, the individual item scores of SUS are shown that female older adult with prior rehabilitation experience perform better in "Learnability" (t = 2.35, p = 0.03) and "Confidence" (t = -3.24, p = 0.01). On the contrary, male older adult without rehabilitation experience are more willing to adopt new technologies (t = -2.73, p = 0.02), and perform better in "Learnability" (t = 2.18, p = 0.04) and "Confidence" (t = -3.75, p < 0.001) with the SSWAD. In addition, the result of the semi-structured interview shows that the operation of the SSWAD is highly flexible, thus reducing older adult burden during the rehabilitation exercise and using them long-term. Conclusion: This novel SSWAD receives consistently positive feedback regardless of the gender or prior rehabilitation experience of elders. The SSWAD could be used as a novel way of home rehabilitation for elders, especially during the COVID-19 pandemic. Older adult can do rehabilitation exercises at home, and physicians could make proper judgments or adjust suitable treatments online according to the sEMG data, which older adult can know their rehabilitation progress at the same time. Most importantly, older adult do not have to go to the hospital every time for rehabilitation, which significantly reduces time and the risk of infection.
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COVID-19 , Dispositivos de Autoayuda , Dispositivos Electrónicos Vestibles , Humanos , Masculino , Femenino , Anciano , Pandemias , COVID-19/epidemiología , Terapia por EjercicioRESUMEN
Diabetic retinopathy (DR) has accounted for major loss of vision in chronic diabetes. Although clinical statistics have shown that early screening can procrastinate or improve the deterioration of the disease, the screening rate remains low worldwide because of the great inconvenience of conventional ophthalmoscopic examination. Instead, tear fluid that contains rich proteins caused by direct contact with eyeballs is an ideal substitute to monitor vision health. Herein, an immunofluorescence biosensor enhanced by a photonic crystal (PhC) is presented to handle the trace proteins suspended in the tear fluid. The PhC was constructed by self-assembled nanoparticles with a thin layer of gold coated on top of it. Then, the PC substrate was conjugated with antibodies and placed in a microchannel. When the capillary-driven tear sample flew over the PC substrate, the immunoassay enabled the formation of a sandwich antibody-antigen-antibody configuration for PhC-enhanced immunofluorescence. The use of PhC resulted in a concentration enhancement of more than tenfold compared to non-PhC, while achieving an equivalent signal intensity. The limit of detection for the target biomarker, lipocalin-1 (LCN-1), reached nearly 3 µg/ml, and the turnaround time of each detection was 15 min. Finally, a preclinical evaluation was conducted using ten tear samples. A clear trend was observed, showing that the concentrations of LCN-1 were at least twofold higher in individuals with chronic diabetes or DR than in healthy individuals. This trend was consistent with their medical conditions. The results provided a direct proof-of-concept for the proposed PhC biosensor in rapid tear-based DR screening.
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The purpose of this study was to compare the therapeutic effects of low-level laser therapy (LLLT) with 808 and 660 nm wavelength on muscle strength and functional outcomes in individuals with knee osteoarthritis (OA). A total of 47 participants were randomly assigned to the 808 nm, 660 nm, and sham control groups. Two LLLT groups received continuous LLLT with a mean power of 300 mW in different wavelengths at the knee joint 15 min a session three days per week for eight weeks, while the control group received the sham LED treatment. The knee strength and functional performance involving 30-s sit-to-stand, 40 m fast-paced walk, stair climbing, and the TUG test were measured at the baseline and one week after the interventions were completed. The results showed that knee extensor strength was more improved in the 808 nm group as compared to the 660 nm group (p < 0.001, d = 0.57) and the sham control (p < 0.001, d = 0.40), while increased flexor strength was demonstrated in the 808 nm (p = 0.009, d = 0.67) and sham control groups (p < 0.001, d = 0.97). The number of 30-s sit-to-stand was increased only in the 660 nm group (p = 0.006, d = 0.49). All three groups exhibited improvements in the other three functional performance-based tests after the interventions with no statistically significant differences among the groups. In conclusion, both intervention groups improved muscle strength and functional performance as compared to the control group. The 808 nm wavelength group showed better results in knee extensor strength. Therefore, laser therapy is suggested to be integrated into rehabilitation programs to improve muscle strength and functional performance in the population with knee OA.
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Terapia por Luz de Baja Intensidad , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla , Fuerza Muscular/fisiología , Osteoartritis de la Rodilla/radioterapiaRESUMEN
BACKGROUND: When a fracture goes into or around a joint, it usually damages the cartilage at the ends of bones and other joint tissue. As a result, the affected joints are prone to traumatic arthritis, leading to stiffness. Repairing bone damage, maintaining joint integrity, and avoiding subchondral and metaphyseal defects caused by comminuted fractures is often a great challenge for orthopedic surgeons. Tissue engineering of synthetic bone substitutes has proven beneficial to the attachment and proliferation of bone cells, promoting the formation of mature tissues with sufficient mechanical strength and has become a promising alternative to autograft methods. The purpose of this study is to retrospectively evaluate the clinical outcome and efficacy of a novel synthetic, highly biocompatible, and fully resorbable Ca/P/S-based bone substitute based on medical image findings. MATERIALS AND METHODS: A synthetic, inorganic and highly porous Ca/P/S-based bone-substituting material (Ezechbone® Granule, CBS-400) has been developed by National Cheng-Kung University. We collected fourteen cases of complex intra- and peri-articular fractures with Ezechbone® Granule bone grafting between 2019/11 and 2021/11. We studied the evidence of bone healing by reviewing, interpreting and analyzing the medical image recordings. RESULTS: In the present study, CBS-400 was observed to quickly integrate into surrounding bone within three weeks after grafting during the initial callus formation of the early stage of repair. All of these cases healed entirely within three months. In addition, the patient may return to daily life function after 3.5 months of follow-up and rehabilitation treatment. CONCLUSIONS: Ezechbone® Granule CBS-400 was proved capable of promoting bone healing and early rehabilitation to prevent soft tissue adhesions and joint contractures. Moreover, it has a high potential for avoiding ectopic bone formation or abnormal synostosis. TRIAL REGISTRATION: The Institutional Review Board at National Cheng Kung University Hospital (NCKUH) approved the study protocol (A-ER-109-031, 3-13-2020).
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Sustitutos de Huesos , Fracturas Conminutas , Fracturas Intraarticulares , Humanos , Sustitutos de Huesos/uso terapéutico , Estudios Retrospectivos , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Trasplante Óseo/métodosRESUMEN
Scaphoid fractures frequently appear in injury radiograph, but approximately 20% are occult. While there are few studies in the fracture detection of X-ray scaphoid images, their effectiveness is insignificant in detecting the scaphoid fractures. Traditional image processing technology had been applied to segment interesting areas of X-ray images, but it always suffered from the requirements of manual intervention and a large amount of computational time. To date, the models of convolutional neural networks have been widely applied to medical image recognition; thus, this study proposed a two-stage convolutional neural network to detect scaphoid fractures. In the first stage, the scaphoid bone is separated from the X-ray image using the Faster R-CNN network. The second stage uses the ResNet model as the backbone for feature extraction, and uses the feature pyramid network and the convolutional block attention module to develop the detection and classification models for scaphoid fractures. Various metrics such as recall, precision, sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) are used to evaluate our proposed method's performance. The scaphoid bone detection achieved an accuracy of 99.70%. The results of scaphoid fracture detection with the rotational bounding box revealed a recall of 0.789, precision of 0.894, accuracy of 0.853, sensitivity of 0.789, specificity of 0.90, and AUC of 0.920. The resulting scaphoid fracture classification had the following performances: recall of 0.735, precision of 0.898, accuracy of 0.829, sensitivity of 0.735, specificity of 0.920, and AUC of 0.917. According to the experimental results, we found that the proposed method can provide effective references for measuring scaphoid fractures. It has a high potential to consider the solution of detection of scaphoid fractures. In the future, the integration of images of the anterior-posterior and lateral views of each participant to develop more powerful convolutional neural networks for fracture detection by X-ray radiograph is probably important to research.
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Sarcopenia is a wild chronic disease among elderly people. Although it does not entail a life-threatening risk, it will increase the adverse risk due to the associated unsteady gait, fall, fractures, and functional disability. The import factors in diagnosing sarcopenia are muscle mass and strength. The examination of muscle mass must be carried in the clinic. However, the loss of muscle mass can be improved by rehabilitation that can be performed in non-medical environments. Electronic impedance myography (EIM) can measure some parameters of muscles that have the correlations with muscle mass and strength. The goal of this study is to use machine learning algorithms to estimate the total mass of thigh muscles (MoTM) with the parameters of EIM and body information. We explored the seven major muscles of lower limbs. The feature selection methods, including recursive feature elimination (RFE) and feature combination, were used to select the optimal features based on the ridge regression (RR) and support vector regression (SVR) models. The optimal features were the resistance of rectus femoris normalized by the thigh circumference, phase of tibialis anterior combined with the gender, and body information, height, and weight. There were 96 subjects involved in this study. The performances of estimating the MoTM used the regression coefficient (r2) and root-mean-square error (RMSE), which were 0.800 and 0.929, and 1.432 kg and 0.980 kg for RR and SVR models, respectively. Thus, the proposed method could have the potential to support people examining their muscle mass in non-medical environments.
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Sarcopenia , Anciano , Algoritmos , Impedancia Eléctrica , Humanos , Aprendizaje Automático , Músculo Esquelético/fisiología , Miografía/métodos , Sarcopenia/diagnósticoRESUMEN
Background. Embedding mirror therapy within a virtual reality (VR) system may have a superior effect on motor remediation for chronic stroke patients. Objective. The objective is to investigate the differences in the effects of using conventional occupational therapy (COT), mirror therapy (MT), and VR-based MT (VR-MT) training on the sensorimotor function of the upper limb in chronic stroke patients. Methods. This was a single-blinded randomized controlled trial. A total of 54 participants, including chronic stroke patients, were randomized into a COT, MT, or VR-MT group. In addition to 20-minute sessions of task-specific training, patients received programs of 30 minutes of VR-MT, 30 minutes of MT, and 30 minutes of COT, respectively, in the VR-MT, MT, and COT groups twice a week for 9 weeks. The Fugl-Meyer motor assessment for the upper extremities (FM-UE; primary outcome), Semmes-Weinstein monofilament, motor activity log, modified Ashworth scale, and the box and block test were recorded at pre-treatment, post-intervention, and 12-week follow-up. Results. Fifty-two participants completed the study. There was no statistically significant group-by-time interaction effects on the FM-UE score (generalized estimating equations, (GEE), P = .075). Meanwhile, there were statistically significant group-by-time interaction effects on the wrist sub-score of the FM-UE (GEE, P = .012) and the result of box and block test (GEE, P = .044). Conclusions. VR-MT seemed to have potential effects on restoring the upper extremity motor function for chronic stroke patients. However, further confirmatory studies are warranted for the rather weak evidence of adding VR to MT on improving primary outcome of this study. Clinical trial registration: NCT03329417.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Realidad Virtual , Humanos , Terapia del Movimiento Espejo , Recuperación de la Función , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
OBJECTIVE: Neovascularization of injured tendons prolongs the proliferative phase of healing, but prolonged neovascularization may cause improper healing and pain. Currently, ultrasound Doppler imaging is used for measuring the neovascularization of injured tendons (e.g., Achilles tendon). However, the resolution of state-of-the-art clinical ultrasound machines is insufficient for visualizing the neovascularization in finger tendons. In this study, a high-frequency micro-Doppler imaging (HFµDI) based on 40-MHz ultrafast ultrasound imaging was proposed for visualizing the neovascularization in injured finger tendons during multiple rehabilitation phases. METHOD: The vessel visibility was enhanced through a block-wise singular value decomposition filter and several curvilinear structure enhancement strategies, including the bowler-hat transform and Hessian-based vessel enhancement filtering. HFµDI was verified through small animal kidney and spleen imaging because the related vessel structure patterns of mice are well studied. Five patients with finger tendon injuries underwent HFµDI examination at various rehabilitation phases after surgery (weeks 11-56), and finger function evaluations were performed for comparisons. RESULTS: The results of small animal experiments revealed that the proposed HFµDI provides excellent microvasculature imaging performance; the contrast-to-noise ratio of HFµDI was approximately 15 dB higher than that of the conventional singular value decomposition filter, and the minimum detectable vessel size for mouse kidney was 35 µm without the use of contrast agent. In the human study, neovascularization was clearly observed in injured finger tendons during the early phase of healing (weeks 11-21), but it regressed from week 52 to 56. Finger rehabilitation appears to help reduce neovascularization; neovascular density decreased by approximately 1.8%-8.0% in participants after 4 weeks of rehabilitation. CONCLUSION: The experimental results verified the performance of HFµDI for microvasculature imaging and its potential for injured finger tendon evaluations.
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Tendón Calcáneo , Traumatismos de los Tendones , Tendón Calcáneo/diagnóstico por imagen , Tendón Calcáneo/lesiones , Animales , Humanos , Ratones , Neovascularización Patológica/diagnóstico por imagen , Traumatismos de los Tendones/diagnóstico por imagen , Ultrasonografía , Ultrasonografía Doppler/métodosRESUMEN
A triangular configuration with three parallel cannulated screws is an established treatment for fixing transverse patellar fractures; however, the stability achieved with this approach is slightly lower than that attained with cannulated screws combined with anterior wiring. In the present study, triangular configurations were modified by partially or totally replacing the cannulated screws with headless compression screws (HCSs). Through finite element simulation involving a model of distal femoral, patellar, and proximal tibial fractures, the mechanical stability levels of the modified triangular configurations were compared with that of two cannulated screws combined with anterior wiring. Four triangular screw configurations were developed: three HCSs in a forward and backward triangular configuration, two deep cannulated screws along with one superficial HCS, and two superficial cannulated screws with one deep HCS. Also considered were two parallel cannulated screws (inserted superficially or deeply) combined with anterior wiring. The six approaches were all examined in full knee extension and 45° flexion under physiological loading. The highest stability was obtained with the three HCSs in a backward triangular configuration, as indicated by the least fragment displacement and the smallest fracture gap size. In extension and flexion, this size was smaller than that observed under the use of two deeply placed parallel cannulated screws with anterior wiring by 50.3% (1.53 vs. 0.76 mm) and 43.2% (1.48 vs. 0.84 mm), respectively. Thus, the use of three HCSs in a backward triangular configuration is recommended for the fixation of transverse patellar fractures, especially without the use of anterior wiring.
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Tornillos Óseos , Fracturas Óseas , Fenómenos Biomecánicos , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Humanos , Rótula/cirugía , Rango del Movimiento ArticularRESUMEN
Tendon injuries lead to tendon stiffness, which impairs skeletal muscle movement. Most studies have focused on patellar or Achilles tendons by using ultrasound elastography. Only a few studies have measured the stiffness of hand tendons because their thickness is only 1-2 mm, rendering clinical ultrasound elastography unsuitable for mapping hand tendon stiffness. In this study, a high-frequency ultrasound shear elastography (HFUSE) system was proposed to map the shear wave velocity (SWV) of hand flexor tendons. A handheld vibration system that was coaxially mounted with an external vibrator on a high-frequency ultrasound (HFUS) array transducer allowed the operators to scan hand tendons freely. To quantify the performance of HFUSE, six parameters were comprehensively measured from homogeneous, two-sided, and three-sided gelatin phantom experiments: bias, precision, lateral resolution, contrast, contrast-to-noise ratio (CNR), and accuracy. HFUSE demonstrated an excellent resolution of [Formula: see text] to distinguish the local stiffness of thin phantom (thickness: 1.2 mm) without compromising bias, precision, contrast, CNR, and accuracy, which has been noted with previous systems. Human experiments involved four patients with hand tendon injuries who underwent ≥2 months of rehabilitation. Using HFUSE, two-dimensional SWV images of flexor tendons could be clearly mapped for healthy and injured tendons, respectively. The findings demonstrate that HFUSE can be a promising tool for evaluating the elastic properties of the injured hand tendon after surgery and during rehabilitation and thus help monitor progress.
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Tendón Calcáneo , Diagnóstico por Imagen de Elasticidad , Traumatismos de los Tendones , Tendón Calcáneo/diagnóstico por imagen , Mano/diagnóstico por imagen , Humanos , Fantasmas de ImagenRESUMEN
BACKGROUND: Carpal Tunnel Syndrome (CTS) is an idiopathic fibrotic disorder. Fibrosis in the subsynovial connective tissues (SSCT) of CTS and many other fibrotic diseases is mediated by Transforming growth factor ß (TGF-ß). Recently monocyte chemoattractant protein-1 (MCP-1) a cytokine involved in cellular recruitment has been suggested to regulate TGF-ß activity. It is related to the onset of diseases which are caused by fibrosis, such as idiopathic pulmonary fibrosis, renal fibrosis, and systemic scleroderma. In this study, we evaluated the effect of the MCP-1 synthesis inhibitor, Bindarit, on primary cultures of fibroblasts from the SSCT of five CTS patients. METHODS: Fibroblasts were treated with Bindarit (10 µM, 50 µM, 100 µM, or 300 µM). Responses to inhibitors were evaluated by regulation of CTS fibrosis-associated genes, fibrosis gene array and Smad luciferase reporter assay. We also assessed the combination effect of Bindarit and SD208, a TGF-ß receptor type 1 inhibitor on TGF-ß signaling. RESULTS: Collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 expression were significantly down-regulated by Bindarit (300 µM) compared to vehicle control. In the fibrosis array, expression of inhibin beta E chain precursor (INHBE), beta actin (ACTB), endothelin 1 (EDN1) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) were significantly down-regulated, and integrin beta-3 (ITGB3) was significantly up-regulated by Bindarit (300 µM). Smad signal transduction activation was significantly down-regulated by Bindarit (300 µM) and/or SD208 (1 µM) with TGF-ß1 compared to vehicle control with TGF-ß1. CONCLUSIONS: These results suggest that Bindarit in combination with SD208 may be beneficial as medical therapy for the SSCT fibrosis associated with CTS.
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Síndrome del Túnel Carpiano , Quimiocina CCL2 , Síndrome del Túnel Carpiano/tratamiento farmacológico , Quimiocina CCL2/antagonistas & inhibidores , Colágeno Tipo III , Fibroblastos , Fibrosis , Humanos , Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta1RESUMEN
The CYP3A5 gene polymorphism accounts for the majority of inter-individual variability in tacrolimus pharmacokinetics. We found that the basal expression of CYP3A5 in donor grafts also played a significant role in tacrolimus metabolism under the same genetic conditions after pediatric liver transplantation. Thus, we hypothesized that some potential epigenetic factors could affect CYP3A5 expression and contributed to the variability. We used a high-throughput functional screening for miRNAs to identify miRNAs that had the most abundant expression in normal human liver and could regulate tacrolimus metabolism in HepaRG cells and HepLPCs. Four of these miRNAs (miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26-5p) were selected for testing. We found that these miRNAs inhibited tacrolimus metabolism that was dependent on CYP3A5. Putative miRNAs targeting key drug-metabolizing enzymes and transporters (DMETs) were selected using an in silico prediction algorithm. Luciferase reporter assays and functional studies showed that miR-26b-5p inhibited tacrolimus metabolism by directly regulating CYP3A5, while miR-29a-5p, miR-99a-5p, and miR-532-5p targeted HNF4α, NR1I3, and NR1I2, respectively, in turn regulating the downstream expression of CYP3A5; the corresponding target gene siRNAs markedly abolished the effects caused by miRNA inhibitors. Also, the expression of miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p in donor grafts were negatively correlated with tacrolimus C/D following pediatric liver transplantation. Taken together, our findings identify these miRNAs as novel regulators of tacrolimus metabolism.
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Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Inmunosupresores/farmacocinética , Trasplante de Hígado , Hígado/enzimología , MicroARNs , Tacrolimus/farmacocinética , Trasplantes/enzimología , Adulto , Línea Celular , Femenino , Humanos , Lactante , Hígado/metabolismo , Masculino , Trasplantes/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Two parallel cannulated screws along with an anterior wire to construct a tension band is a popular approach in transverse patellar fractures. However, the optimal screw proximity, either deep or superficial screw placements, remains controversial. Hence, a new concept of the addition of a third screw to form a triangular configuration along with the original two parallel screws was proposed in this study. Therefore, the biomechanical effect of the additional third screw on the stability of the fractured patella was investigated with finite element (FE) simulation. METHODS: An FE knee model including the distal femur, proximal tibia, and fractured patella (type AT/OTA 34-C) was developed in this study. Four different screw configurations, including two parallel cannulated screws with superficial (5-mm proximity) and deep (10-mm proximity) placements and two parallel superficial screws plus a third deep screw, and two parallel deep screws plus a third superficial screw, with or without the anterior wire, were considered for the simulation. RESULTS: Results indicated that the addition of a third screw increased stability by reducing the dorsal gap opening when two parallel screws were deeply placed, particularly on the fractured patella without an anterior wire. However, the third screw was of little value when two parallel screws were superficially placed. In the existence of two deep parallel screws and the anterior wire, the third screw reduced the gap opening by 23.5% (from 1.15 mm to 0.88 mm) and 53.6% (from 1.21 mm to 0.61 mm) in knee flexion 45° and full extension, respectively. Furthermore, in the absence of the anterior wire, the third screw reduced the gap opening by 73.5% (from 2 mm to 0.53 mm) and 72.2% (from 1.33 mm to 0.37 mm) in knee flexion 45° and full extension, respectively. CONCLUSION: Based on the results, a third cannulated screw superficially placed (5-mm proximity) is recommended to increase stability and maintain contact of the fractured patella, fixed with two parallel cannulated screws deeply placed (10-mm proximity), particularly when an anterior wire was not used. Furthermore, the third screw deeply placed is not recommended in a fractured patella with two parallel superficial screws.
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Fracturas Óseas , Rótula , Fenómenos Biomecánicos , Tornillos Óseos , Hilos Ortopédicos , Fijación Interna de Fracturas , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Rótula/diagnóstico por imagen , Rótula/cirugíaRESUMEN
BACKGROUND: Lateral hinge fracture (LHF) is associated with nonunion and plate breakage in high tibial osteotomy (HTO). Mechanical studies investigating fixation strategies for LHFs to restore stability and avoid plate breakage are absent. This study used computer simulation to compare mechanical stabilities in HTO for different LHFs fixed with medial and bilateral locking plates. METHODS: A finite element knee model was created with HTO and three types of LHF, namely T1, T2, and T3 fractures, based on the Takeuchi classification. Either medial plating or bilateral plating was used to fix the HTO with LHFs. Furthermore, the significance of the locking screw at the combi hole (D-hole) of the medial TomoFix plate was evaluated. RESULTS: The osteotomy gap shortening distance increased from 0.53 to 0.76, 0.79, and 0.72 mm after T1, T2, and T3 LHFs, respectively, with medial plating only. Bilateral plating could efficiently restore stability and maintain the osteotomy gap. Furthermore, using the D-hole screw reduced the peak stress on the medial plate by 28.7% (from 495 to 353 MPa), 26.6% (from 470 to 345 MPa), and 32.6% (from 454 to 306 MPa) in T1, T2, and T3 LHFs, respectively. CONCLUSION: Bilateral plating is a recommended strategy to restore HTO stability in LHFs. Furthermore, using a D-hole locking screw is strongly recommended to reduce the stress on the medial plate for lowering plate breakage risk.
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Placas Óseas , Simulación por Computador , Fijación Interna de Fracturas/métodos , Osteotomía/métodos , Fracturas de la Tibia/cirugía , Fenómenos Biomecánicos , Tornillos Óseos , Análisis de Elementos Finitos , Humanos , Tibia/cirugíaRESUMEN
Carpal tunnel syndrome commonly occurs in individuals working in occupations that involve use of vibrating manual tools or tasks with highly repetitive and forceful manual exertion. In recent years, carpal tunnel syndrome has been evaluated by ultrasound imaging that monitors median nerve movement. Conventional image analysis methods, such as the active contour model, are typically used to expedite automatic segmentation of the median nerve, but these usually suffer from an arduous manual intervention. We propose a new convolutional neural network framework for localization and segmentation of the median nerve, called DeepNerve, that is based on the U-Net model. DeepNerve integrates the characteristics of MaskTrack and convolutional long short-term memory to effectively locate and segment the median nerve. On the basis of experimental results, the proposed model achieved high performance and generated average Dice measurement, precision, recall and F-score values of 0.8975, 0.8912, 0.9119 and 0.9015, respectively. The segmentation results of DeepNerve were significantly improved in comparison with those of conventional active contour models. Additionally, the results of Student's t-test revealed significant differences in four deformation measurements of the median nerve, including area, perimeter, aspect ratio and circularity. We conclude that the proposed DeepNerve not only generates satisfactory results for localization and segmentation of the median nerve, but also creates more promising measurements for applications in clinical carpal tunnel syndrome diagnosis.
Asunto(s)
Síndrome del Túnel Carpiano/diagnóstico por imagen , Nervio Mediano/diagnóstico por imagen , Redes Neurales de la Computación , Adolescente , Adulto , Humanos , Masculino , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Trigger finger is a common hand disease, which is caused by a mismatch in diameter between the tendon and the pulley. Ultrasound images are typically used to diagnose this disease, which are also used to guide surgical treatment. However, background noise and unclear tissue boundaries in the images increase the difficulty of the process. To overcome these problems, a computer-aided tool for the identification of finger tissue is needed. RESULTS: Two datasets were used for evaluation: one comprised different cases of individual images and another consisting of eight groups of continuous images. Regarding result similarity and contour smoothness, our proposed deeply supervised dilated fully convolutional DenseNet (D2FC-DN) is better than ATASM (the state-of-art segmentation method) and representative CNN methods. As a practical application, our proposed method can be used to build a tendon and synovial sheath model that can be used in a training system for ultrasound-guided trigger finger surgery. CONCLUSION: We proposed a D2FC-DN for finger tendon and synovial sheath segmentation in ultrasound images. The segmentation results were remarkably accurate for two datasets. It can be applied to assist the diagnosis of trigger finger by highlighting the tissues and generate models for surgical training systems in the future. METHODS: We propose a novel finger tendon segmentation method for use with ultrasound images that can also be used for synovial sheath segmentation that yields a more complete description for analysis. In this study, a hybrid of effective convolutional neural network techniques are applied, resulting in a deeply supervised dilated fully convolutional DenseNet (D2FC-DN), which displayed excellent segmentation performance on the tendon and synovial sheath.
Asunto(s)
Aprendizaje Profundo , Dedos/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Tendones/diagnóstico por imagen , Humanos , Membranas/diagnóstico por imagen , UltrasonografíaRESUMEN
PURPOSE: Hand tendon injuries caused by various accidents are common in emergency departments. The assessment of tendon properties is crucial for evaluating the effectiveness of therapy or rehabilitation during recovery after hand injuries. Many recent studies have indicated that the shear wave velocity (SWV) of tendons is related to their stiffness. However, measurement of SWV of hand tendon is still a challenge because the small size of tendon and the limitation of existing ultrasound systems for detecting fast SWV. METHODS: We propose a high-frequency ultrasound (HFUS) elastography system using an external vibrator to measure the SWV of the extensor digitorum communis (EDC) tendon. First, animal studies were performed by measuring the SWV and stress of porcine tendons using the proposed HFUS elastography and materials testing systems respectively. In the human experiment, SWVs were measured during hand extension and flexion. The applied stress from a finger during the movements was recorded synchronously by using a load cell. RESULTS: The experimental results reveal that a favorable linear correction (R2 of 0.96) was obtained between tendon SWV and stress in animal studies. In the human (hand) EDC tendon experiments, the SWV increased with the extension and flexion of the hand. The SWV of the EDC tendon was in the range of 20 to 135 m/s as the applied force from the finger of a healthy human increased to 50% maximal voluntary contraction. CONCLUSIONS: All the experimental results show that the proposed HFUS elastography system can be used to characterize the EDC tendon and has potential use for evaluating tendon stiffness during recovery after hand injures.
Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Fenómenos Mecánicos , Tendones/diagnóstico por imagen , Ondas Ultrasónicas , Animales , Porcinos , Resistencia a la Tracción , VibraciónRESUMEN
OBJECTIVE: Injuries to the hands, wrists, and fingers often involve damage to the tendons. The ability to measure tendon movements during the rehabilitation process can provide clinicians with important information in the quantification of tendon injuries. Conventionally, the tendon is considered a single spring-like structure during force transmission, and its twisted structure is neglected. Recently, clinicians believed that the twisted fiber structure (which enables tendon rotation during movement) of the tendon can provide it with a degree of elasticity and improve the efficiency of force transmission. However, observation of the hand tendon rotation in vivo by using the current imaging modalities is difficult. METHODS: In this study, a 40-MHz high-frequency vector Doppler imaging (HFVDI) was used to visualize the movement of the hand tendon during muscle contraction. The performance of HFVDI was verified using a rotation phantom experiment. Two human experiments were designed in the present study: 1) participants were allowed to bend their distal and proximal interphalangeal (DIP and PIP) joints of fingers freely and 2) the PIP joint of the finger was fixed such that only the DIP could be moved. The HFVDIs of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were obtained in the transverse and longitudinal views to observe the movements of the hand tendon during finger movements. RESULTS: The average longitudinal displacements of the FDS and FDP were approximately 3-4 mm for free bending of the finger; however, it was reduced when only the DIP was moved. The rotational phenomenon of the FDS and FDP tendons was observed in the transverse view, which demonstrated the different rotational behaviors of the FDS and FDP fibers during muscle contraction. CONCLUSION: All the results validated the potential of HFVDI as a novel tool for visualizing tendon rotation and would be useful in providing quantitative information regarding tendon function to determine the rehabilitation process following injuries.