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OBJECTIVE: The changes in neural drive to muscles associated with modulation of inter-muscular coordination in the upper extremity have not yet been investigated. Such information could help elucidate the neural mechanisms behind motor skill learning. METHODS: Six young, neurologically healthy participants underwent a six-week training protocol to decouple two synergist elbow flexor muscles as a newly learned motor skill in the isometric force generation in upward and medial directions. Concurrent electroencephalography and surface electromyography from twelve upper extremity muscles were recorded in two conditions (As-Trained & Habitual) across two assessments (Week 0 vs. Week 6). Changes to inter-muscular connectivity (IMC), functional muscle networks, cortico-muscular connectivity (CMC), cortico-cortical connectivity (CCC) as well as functional brain network controllability (FBNC) associated with the modulation of inter-muscular coordination patterns were assessed to provide a perspective on the neural mechanisms for the newly learned motor skills. RESULTS: Significant decreases in elbow flexor IMC, CMC, and increases in CCC were observed. No significant changes were observed for FBNC. CONCLUSION: The results of this study suggest that modulating the inter-muscular coordination of the elbow flexor muscle synergy during isometric force generation is associated with multiple yet distinct changes in functional connectivity across the central and peripheral perspectives. SIGNIFICANCE: Understanding the neural mechanisms of modulating inter-muscular coordination patterns can help inform motor rehabilitation regimens.
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BACKGROUND AND PURPOSE: Only limited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH). Glabridin, a promising anti-obesity candidate, has only limited druggability due to its low in vivo chemical stability and bioavailability. Therefore, we developed vutiglabridin (VUTI), which is based on a glabridin backbone, and investigated its mechanism of action in treating NASH in animal models. EXPERIMENTAL APPROACH: Anti-NASH effects of VUTI were determined in in vitro fatty liver models, spheroids of primary human hepatocytes and L02 normal liver cell lines. To identify VUTI possible cellular target/s, biotin-labelled VUTI was synthesized and underwent chemical proteomic analysis. Further, the evaluation of VUTI therapeutic efficacy was carried out using an amylin-NASH and high-fat (HF) diet-induced obese (DIO) mouse models. This was carried out using transcriptomic, lipidomic and proteomic analyses of the livers from the amylin-NASH mouse model. KEY RESULTS: VUTI treatment markedly reduces hepatic steatosis, fibrosis and inflammation by promoting lipid catabolism, activating autophagy and improving mitochondrial dysfunction, all of which are hallmarks of effective NASH treatment. The cellular target of VUTI was identified as paraoxonase 2 (PON2), a newly proposed protein target for the treatment of NASH, VUTI enhanced PON2 activity. The results using PON2 knockdown cells demonstrated that PON2 is important for VUTI- activation of autophagy, promoting mitochondrial function, decreasing oxidative stress and alleviating lipid accumulation under lipotoxic condition. CONCLUSION AND IMPLICATIONS: Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH.
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Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
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Proteínas Mutadas de Ataxia Telangiectasia , Citidina Desaminase , Antígenos de Histocompatibilidade Menor , Neoplasias da Bexiga Urinária , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem/metabolismo , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismoRESUMO
OBJECTIVE: KINDLE-Korea is part of a real-world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The KINDLE was an international real-world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE-Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. RESULTS: A total of 461 patients were enrolled. The median age was 66 years (range: 24-87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)-based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. CONCLUSION: This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.
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Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Quimiorradioterapia , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
The finger workspace is crucial for performing various grasping tasks. Thus, various soft rehabilitation gloves have been developed to assist individuals with paralyzed hands in activities of daily living (ADLs) or rehabilitation training. However, most soft robotic glove designs are insufficient to assist with various hand postures because most of them use an underactuated mechanism for design simplicity. Therefore, this paper presents a methodology for optimizing the design of a high-degree-of-freedom soft robotic glove while not increasing the design complexity. We defined the required functional workspace of the index finger based on ten frequently used grasping postures in ADLs. The design optimization was achieved by simulating the proposed finger-robot model to obtain a comparable workspace to the functional workspace. In particular, the moment arm length for extension was optimized to facilitate the grasping of large objects (precision disk and power sphere), whereas a torque-amplifying routing design was implemented to aid the grasping of small objects (lateral pinch and thumb-two-finger pinch). The effectiveness of the optimized design was validated through testing with a stroke survivor and comparing the assistive workspace. The observed workspace demonstrated that the optimized glove design could assist with nine out of the ten targeted grasping posture functional workspaces. Furthermore, the assessment of the grasping speed and force highlighted the glove's usability for various rehabilitation activities. We also present and discuss a generalized methodology to optimize the design parameters of a soft robotic glove that uses an underactuated mechanism to assist the targeted workspace. Overall, the proposed design optimization methodology serves as a tool for developing advanced hand rehabilitation robots, as it offers insight regarding the importance of routing optimization in terms of the workspace.
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Soft wearable robots have been gaining increasing popularity for enhancing human physical abilities and assisting people who have physical limitations. These robots typically use tendon-driven mechanisms (TDMs) to enable remote actuation to provide better usability with compact design. TDMs comprise an actuator, an end-effector, and a transmission system by using cables or tendons to transfer forces from the actuator to the end-effector. Tendons are typically routed by frictionless guiding tubes to minimize force losses, variations in the force direction, and the volume. To make soft wearable robots even smaller, brakes need to be compacted because brakes are irreplaceable to ensure safety and energy efficiency. This study presents a shape memory alloy-based reactive tubular (SMART) brake for designing a compact and portable TDM-based device. The SMART brake actively adjusts the friction force between the brake and tendon, making it easy to achieve the desired friction state, ranging from low-friction states for free movement to high-friction states for effective braking. The brake is designed in a tubular shape, serving multifunctions as both a brake and a guiding tube. The brake's performance and theoretical model were validated through experiments and demonstrated by two wearable devices. The brake could hold a significant brake force of 19.37 N/11 mm while weighing only 0.3 g. These findings have major implications for the future development of TDM-based devices and soft wearable robots, paving the way for enhanced system portability, safety, and energy efficiency.
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Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non-small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.
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During the postoperative hand rehabilitation period, it is recommended that the repaired flexor tendons be continuously glided with sufficient tendon excursion and carefully managed protection to prevent adhesion with adjacent tissues. Thus, finger joints should be passively mobilized through a wide range of motion (ROM) with physiotherapy. During passive mobilization, sequential flexion of the metacarpophalangeal (MCP) joint followed by the proximal interphalangeal (PIP) joint is recommended for maximizing tendon excursion. This paper presents a lightweight device for postoperative flexor tendon rehabilitation that uses a single motor to achieve sequential joint flexion movement. The device consists of an orthosis, a cable, and a single motor. The degree of spatial stiffness and cable path of the orthosis were designed to apply a flexion moment to the MCP joint prior to the PIP joint. The device was tested on both healthy individuals and a patient who had undergone flexor tendon repair surgery, and both flexion and extension movement could be achieved with a wide ROM and sequential joint flexion movement using a single motor.
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Articulações dos Dedos , Tendões , Humanos , Tendões/cirurgia , Articulações dos Dedos/cirurgia , Movimento , Aparelhos Ortopédicos , Amplitude de Movimento ArticularRESUMO
The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-ß-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.
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Stroke is a debilitating condition that leads to a loss of motor function, inability to perform daily life activities, and ultimately worsening quality of life. Robot-based rehabilitation is a more effective method than conventional rehabilitation but needs to accurately recognize the patient's intention so that the robot can assist the patient's voluntary motion. This study focuses on recognizing hand grasp motion intention using high-density electromyography (HD-EMG) in patients with chronic stroke. The study was conducted with three chronic stroke patients and involved recording HD-EMG signals from the muscles involved in hand grasp motions. The adaptive onset detection algorithm was used to accurately identify the start of hand grasp motions accurately, and a convolutional neural network (CNN) was trained to classify the HD-EMG signals into one of four grasping motions. The average true positive and false positive rates of the grasp onset detection on three subjects were 91.6% and 9.8%, respectively, and the trained CNN classified the grasping motion with an average accuracy of 76.3%. The results showed that using HD-EMG can provide accurate hand grasp motion intention recognition in chronic stroke patients, highlighting the potential for effective robot-based rehabilitation.
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Mãos , Acidente Vascular Cerebral , Humanos , Eletromiografia/métodos , Mãos/fisiologia , Intenção , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Força da Mão/fisiologiaRESUMO
Shoulder impingement syndrome can be caused by a muscle imbalance around the shoulder joint. It would be beneficial for therapy to implement rehabilitation exercises based on intermuscular coordination in order to achieve muscle balance. This study presents the muscle synergy characteristics of patients with shoulder impingement syndrome, which can be used to develop rehabilitation exercises. During pick and place task, the muscle synergy obtained from eight shoulder muscles in patients and healthy subjects was compared. The experimental results revealed that patients have low contributed muscle synergy structures for the serratus anterior and infraspinatus.Clinical relevance- This proposes that patients with shoulder impingement syndrome may have abnormal muscle synergy structure which can be used for assessment.
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Síndrome de Colisão do Ombro , Articulação do Ombro , Humanos , Síndrome de Colisão do Ombro/reabilitação , Eletromiografia/métodos , Ombro/fisiologia , Articulação do Ombro/fisiologia , Manguito Rotador/fisiologiaRESUMO
Abnormal intermuscular coordination is a major stroke-induced functional motor impairment in the upper extremity (UE). Previous studies have computationally identified the abnormalities in the intermuscular coordination in the stroke-affected UE and their negative impacts on motor outputs. Therefore, targeting the aberrant muscle synergies has the potential as an effective approach for stroke rehabilitation. Recently, we verified the modifiability of the naturally expressed muscle synergies of young able-bodied adults in UE through an electromyographic (EMG) signal-guided exercise protocol. This study tested if an EMG-guided exercise will induce new muscle synergies, alter the associated intermuscular connectivity, and improve UE motor outcome in stroke-affected UE with moderate-to-severe motor impairment. The study used the six-week isometric EMG signal-guided exercise protocol that focused on independently activating two specific muscles, the biceps and brachioradialis, to develop new muscle activation groups. The study found that both the stroke and age-matched, able-bodied groups were able to develop new muscle coordination patterns through the exercise while habitual muscle activation was still available, which led to improvements in the motor control of the trained arm. In addition, the results provided preliminary evidence of increased intermuscular connectivity between targeted muscles in the beta-band frequencies for stroke patients after training, suggesting a modulation of the common neural drive. These findings suggest that our isometric exercise protocol has the potential to improve stroke survivors' performance of UE in their activities in daily lives (ADLs) and, ultimately, their quality of life through expanding their repertoire of intermuscular coordination.Clinical Relevance- This study shows the feasibility of expanding the intermuscular coordination pattern in stroke-affected UE through an isometric EMG-guided exercise which positively affects task performance and intermuscular connectivity.
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Qualidade de Vida , Acidente Vascular Cerebral , Adulto , Humanos , Eletromiografia , Projetos Piloto , Extremidade SuperiorRESUMO
Abnormal intermuscular coordination in stroke-affected upper limbs contributes to motor deficits after stroke. In particular, abnormalities in the activation of upper limb muscle synergies after stroke were demonstrated for endpoint force control during isokinetic exercises. This study aimed to investigate the feasibility of isokinetic training to alter these abnormal synergy activations and improve motor control. Muscle synergies and Wolf Motor Function Test Functional Ability Scale (WMFT-FAS) score were compared before and after three weeks of electromyography-based training. The proposed training changed the synergy activation and improved the WMFT-FAS score in a chronic stroke survivor while preserving the muscle weights of the synergies.Clinical Relevance- This study presents the feasibility of neuromuscular training to modify the activation of upper limb muscle synergies against stroke-specific patterns of intermuscular coordination and improve WMFT-FAS score.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estudos de Viabilidade , Extremidade Superior , Acidente Vascular Cerebral/complicações , MúsculosRESUMO
Brain plasticity plays a significant role in functional recovery after stroke, but the specific benefits of hand rehabilitation robot therapy remain unclear. Evaluating the specific effects of hand rehabilitation robot therapy is crucial in understanding how it impacts brain activity and its relationship to rehabilitation outcomes. This study aimed to investigate the brain activity pattern during hand rehabilitation exercise using functional magnetic resonance imaging (fMRI), and to compare it before and after 3-week hand rehabilitation robot training. To evaluate it, an fMRI experimental environment was constructed to facilitate the same hand posture used in rehabilitation robot therapy. Two stroke survivors participated and the conjunction analysis results from fMRI scans showed that patient 1 exhibited a significant improvement in activation profile after hand rehabilitation robot training, indicative of improved motor function in the bilateral motor cortex. However, activation profile of patient 2 exhibited a slight decrease, potentially due to habituation to the rehabilitation task. Clinical results supported these findings, with patient 1 experiencing a greater increase in FMA score than patient 2. These results suggest that hand rehabilitation robot therapy can induce different brain activity patterns in stroke survivors, which may be linked to patient-specific training outcomes. Further studies with larger sample sizes are necessary to confirm these findings.
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Córtex Motor , Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Robótica/métodos , Imageamento por Ressonância Magnética , Recuperação de Função Fisiológica/fisiologiaRESUMO
The sense of proprioception plays a critical role in motor function by providing a sense of body position and movement. Recent research has highlighted the impact of impaired proprioception on rehabilitation outcomes for stroke patients. To address this issue, various studies have explored the use of vibrotactile feedback to aid and enhance impaired proprioception. Since most studies focused on investigating the characteristics of human proprioceptive position or movement sense, the fixed and cumbersome equipment used for those studies is inappropriate for daily use where compact and portable device is preferred. To address this limitation, we propose a novel vibrotactile feedback method that provides joint-level state information using the cyclic vibrotactile funneling illusion. The proposed method was validated in first experiment with eleven healthy subjects, and the accuracy of proposed method in bi-directional scheme was evaluated through second experiments with three healthy subjects. Our methods demonstrated sufficient ability to transmit proprioceptive position information, making them potentially applicable to various wearable rehabilitation devices, thereby enabling more effective rehabilitation for patients with proprioceptive impairment.
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Ilusões , Humanos , Retroalimentação , Propriocepção , Movimento , PosturaRESUMO
This study investigated the impact of stroke on the control of upper limb endpoint force during isokinetic exercise, a dynamic force-generating task, and its association with stroke-affected muscle synergies. Three-dimensional upper limb endpoint force and electromyography of shoulder and elbow muscles were collected from sixteen chronic stroke survivors and eight neurologically intact adults. Participants were instructed to control the endpoint force direction during three-dimensional isokinetic upper limb movements. The endpoint force control performance was quantitatively evaluated in terms of the coupling between forces in orthogonal directions and the complexity of the endpoint force. Upper limb muscle synergies were compared between participants with varying levels of endpoint force coupling. The stroke survivors generating greater force abnormality than the others exhibited interdependent activation profiles of shoulder- and elbow-related muscle synergies to a greater extent. Based on the relevance of synergy activation to endpoint force control, this study proposes isokinetic training to correct the abnormal synergy activation patterns post-stroke. Several ideas for implementing effective training for stroke-affected synergy activation are discussed.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Adulto , Humanos , Extremidade Superior , Músculo Esquelético/fisiologia , Ombro , Eletromiografia/métodosRESUMO
The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.
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Recently, virtua reality (VR) has been widely utilized with rehabilitation to promote user engagement, which has been shown to induce brain plasticity. In this study, we developed a VR-based hand rehabilitation system consisting of a personalized gesture-controlled rhythm game with vibrotactile feedback and investigated the cortical activation pattern induced by our system using functional near-infrared spectroscopy (fNIRS). Our system provides vibrotactile feedback as the user matches their hand gestures to VR targets customized to their pre-recorded hand gestures. Cortical activation was measured via fNIRS during 420 seconds of alternating gameplay and rest in 11 healthy subjects and one stroke survivor. Regions of interest (ROI) were the prefrontal cortex (PFC), the premotor cortex & the supplementary motor area (PMC&SMA), the primary sensorimotor cortex (SM1), and the somatosensory association cortex (SAC). The mean success rate of gesture matching among healthy subjects was 90 % with a standard deviation of 10.7 %, and the success rate of the stroke survivor was 79.6 %. The averaged cortical activation map for the 11 healthy subjects and the individual cortical activation map for the single stroke survivor showed increased hemodynamic responses of oxygenated hemoglobin (HbO) during the VR-based hand rehabilitation compared to the resting condition. Paired t-test analysis demonstrated a significant increase in HbO activation values in 19 out of 51 channels, corresponding to all ROIs except the left PFC and PMC&SMA, which exhibited high subject variability. The experimental results indicate that the proposed system successfully activated brain areas related to motor planning/execution, multisensory integration, and attention.
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BACKGROUND: Muscle synergies, computationally identified intermuscular coordination patterns, have been utilized to characterize neuromuscular control and learning in humans. However, it is unclear whether it is possible to alter the existing muscle synergies or develop new ones in an intended way through a relatively short-term motor exercise in adulthood. This study aimed to test the feasibility of expanding the repertoire of intermuscular coordination patterns through an isometric, electromyographic (EMG) signal-guided exercise in the upper extremity (UE) of neurologically intact individuals. METHODS: 10 participants were trained for six weeks to induce independent control of activating a pair of elbow flexor muscles that tended to be naturally co-activated in force generation. An untrained isometric force generation task was performed to assess the effect of the training on the intermuscular coordination of the trained UE. We applied a non-negative matrix factorization on the EMG signals recorded from 12 major UE muscles during the assessment to identify the muscle synergies. In addition, the performance of training tasks and the characteristics of individual muscles' activity in both time and frequency domains were quantified as the training outcomes. RESULTS: Typically, in two weeks of the training, participants could use newly developed muscle synergies when requested to perform new, untrained motor tasks by activating their UE muscles in the trained way. Meanwhile, their habitually expressed muscle synergies, the synergistic muscle activation groups that were used before the training, were conserved throughout the entire training period. The number of muscle synergies activated for the task performance remained the same. As the new muscle synergies were developed, the neuromotor control of the trained muscles reflected in the metrics, such as the ratio between the targeted muscles, number of matched targets, and task completion time, was improved. CONCLUSION: These findings suggest that our protocol can increase the repertoire of readily available muscle synergies and improve motor control by developing the activation of new muscle coordination patterns in healthy adults within a relatively short period. Furthermore, the study shows the potential of the isometric EMG-guided protocol as a neurorehabilitation tool for aiming motor deficits induced by abnormal intermuscular coordination after neurological disorders. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRiS) of the Korea National Institute of Health (KCT0005803) on 1/22/2021.
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Articulação do Cotovelo , Extremidade Superior , Adulto , Humanos , Aprendizagem , Músculo Esquelético , AlgoritmosRESUMO
BACKGROUND: Ageing alters the ECM, leading to mitochondrial dysfunction and oxidative stress, which triggers an inflammatory response that exacerbates with age. Age-related changes impact satellite cells, affecting muscle regeneration, and the balance of proteins. Furthermore, ageing causes a decline in NAD+ levels, and alterations in fat metabolism that impact our health. These various metabolic issues become intricately intertwined with ageing, leading to a variety of individual-level diseases and profoundly affecting individuals' healthspan. Therefore, we hypothesize that vutiglabridin capable of alleviating these metabolic abnormalities will be able to ameliorate many of the problems associated with ageing. METHOD: The efficacy of vutiglabridin, which alleviates metabolic issues by enhancing mitochondrial function, was assessed in aged mice treated with vutiglabridin and compared to untreated elderly mice. On young mice, vutiglabridin-treated aged mice, and non-treated aged mice, the Senescence-associated beta-galactosidase staining and q-PCR for ageing marker genes were carried out. Bulk RNA-seq was carried out on GA muscle, eWAT, and liver from each group of mice to compare differences in gene expression in various gene pathways. Blood from each group of mice was used to compare and analyze the ageing lipid profile. RESULTS: SA-ß-gal staining of eWAT, liver, kidney, and spleen of ageing mice showed that vutiglabridin had anti-ageing effects compared to the control group, and q-PCR of ageing marker genes including Cdkn1a and Cdkn2a in each tissue showed that vutiglabridin reduced the ageing process. In aged mice treated with vutiglabridin, GA muscle showed improved homeostasis compared to controls, eWAT showed restored insulin sensitivity and prevented FALC-induced inflammation, and liver showed reduced inflammation levels due to prevented TLO formation, improved mitochondrial complex I assembly, resulting in reduced ROS formation. Furthermore, blood lipid analysis revealed that ageing-related lipid profile was relieved in ageing mice treated with vutiglabridin versus the control group. CONCLUSION: Vutiglabridin slows metabolic ageing mechanisms such as decreased insulin sensitivity, increased inflammation, and altered NAD+ metabolism in adipose tissue in mice experiments, while also retaining muscle homeostasis, which is deteriorated with age. It also improves the lipid profile in the blood and restores mitochondrial function in the liver to reduce ROS generation.