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Search Results (815)

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Keywords = experimental stroke

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19 pages, 1424 KiB  
Article
Development and Testing of a Dual-Driven Piezoelectric Microgripper with High Amplification Ratio for Cell Micromanipulation
by Boyan Lu, Shengzheng Kang, Luyang Zhou, Dewen Hua, Chengdu Yang and Zimeng Zhu
Machines 2024, 12(10), 722; https://doi.org/10.3390/machines12100722 - 12 Oct 2024
Viewed by 284
Abstract
Cell micromanipulation is an important technique in the field of biomedical engineering. Microgrippers play a crucial role in connecting macroscopic and microscopic objects in micromanipulation systems. However, since the operated biological cells are deformable, vulnerable, and typically distributed in sizes ranging from micrometers [...] Read more.
Cell micromanipulation is an important technique in the field of biomedical engineering. Microgrippers play a crucial role in connecting macroscopic and microscopic objects in micromanipulation systems. However, since the operated biological cells are deformable, vulnerable, and typically distributed in sizes ranging from micrometers to millimeters, it poses a huge challenge to microgripper performance. To solve this problem, this paper develops a dual-driven piezoelectric microgripper with a high displacement amplification ratio, large stroke, and parallel gripping. By adopting modular configuration, three kinds of flexure-based mechanisms, including the lever mechanism, Scott–Russell mechanism, and parallelogram mechanism are connected in series to realize three-stage amplification, which effectively makes up for the shortage of small output displacement of the piezoelectric actuator. At the same time, the use of the parallelogram mechanism also isolates the parasitic rotation movement, and realizes the parallel movement of the gripping jaws. In addition, the kinematics, statics, and dynamics models of the microgripper are established by using the pseudo-rigid body and Lagrange methods, and the key geometric parameters are also optimized. Finite element simulation and experimental tests verify the effectiveness of the developed microgripper. The results show that the developed microgripper allows an amplification ratio of 46.4, a clamping stroke of 2180 μm, and a natural frequency of 203.1 Hz. Based on the developed microgripper, the nondestructive micromanipulation of zebrafish embryos is successfully realized. Full article
(This article belongs to the Special Issue Optimization and Design of Compliant Mechanisms)
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<p>Schematic diagram of the developed dual-driven piezoelectric microgripper.</p>
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<p>(<b>a</b>) Distribution of the flexure hinges in the microgripper. (<b>b</b>) Equivalent model of half of the microgripper and its geometric parameters.</p>
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<p>Motion vector diagram of three amplification mechanisms.</p>
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<p>Diagram of changes in displacements and angles of the microgripper.</p>
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<p>Static analysis of the microgripper.</p>
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<p>Static analysis results: (<b>a</b>) <span class="html-italic">X</span>-direction deformation; (<b>b</b>) <span class="html-italic">Y</span>-direction deformation.</p>
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<p>Stress distribution of the microgripper.</p>
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<p>Finite element analysis results for first six modes of the microgripper.</p>
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<p>(<b>a</b>) Experimental setup for cell microgripping. (<b>b</b>) Structure of the developed microgripper. (<b>c</b>) Schematic diagram of cell immobilization.</p>
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<p>Output displacement responses of the microgripper with the applied voltage. (<b>a</b>) The input end. (<b>b</b>) The output end.</p>
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<p>Frequency response of the developed microgripper.</p>
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<p>Closed-loop tracking results of the microgripper. (<b>a</b>,<b>b</b>) Step signal tracking results. (<b>c</b>,<b>d</b>) 1-Hz sinusoidal signal tracking results.</p>
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<p>Microscopic images of cell micromanipulation by the developed microgripper. (<b>a</b>) Before gripping the cell. (<b>b</b>) After gripping the cell. (<b>c</b>) Releasing the cell. From the figure, it is observed that the gripper can clamp and release the cell successfully without mechanical damage.</p>
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<p>(<b>a</b>) Closed -loop control bandwidth of the developed microgripper, where the red dashed lines represent that the bandwidth is 23.1 Hz under the magnitude of −3 dB. (<b>b</b>) Statistical results of cell grasping experiments under different frequencies, where each frequency is repeatedly tested for ten times.</p>
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16 pages, 5805 KiB  
Article
Numerical and Experimental Study of a Wearable Exo-Glove for Telerehabilitation Application Using Shape Memory Alloy Actuators
by Mohammad Sadeghi, Alireza Abbasimoshaei, Jose Pedro Kitajima Borges and Thorsten Alexander Kern
Actuators 2024, 13(10), 409; https://doi.org/10.3390/act13100409 - 11 Oct 2024
Viewed by 377
Abstract
Hand paralysis, caused by conditions such as spinal cord injuries, strokes, and arthritis, significantly hinders daily activities. Wearable exo-gloves and telerehabilitation offer effective hand training solutions to aid the recovery process. This study presents the development of lightweight wearable exo-gloves designed for finger [...] Read more.
Hand paralysis, caused by conditions such as spinal cord injuries, strokes, and arthritis, significantly hinders daily activities. Wearable exo-gloves and telerehabilitation offer effective hand training solutions to aid the recovery process. This study presents the development of lightweight wearable exo-gloves designed for finger telerehabilitation. The prototype uses NiTi shape memory alloy (SMA) actuators to control five fingers. Specialized end effectors target the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints, mimicking human finger tendon actions. A variable structure controller, managed through a web-based Human–Machine Interface (HMI), allows remote adjustments. Thermal behavior, dynamics, and overall performance were modeled in MATLAB Simulink, with experimental validation confirming the model’s efficacy. The phase transformation characteristics of NiTi shape memory wire were studied using the Souza–Auricchio model within COMSOL Multiphysics 6.2 software. Comparing the simulation to trial data showed an average error of 2.76°. The range of motion for the MCP, PIP, and DIP joints was 21°, 65°, and 60.3°, respectively. Additionally, a minimum torque of 0.2 Nm at each finger joint was observed, which is sufficient to overcome resistance and meet the torque requirements. Results demonstrate that integrating SMA actuators with telerehabilitation addresses the need for compact and efficient wearable devices, potentially improving patient outcomes through remote therapy. Full article
(This article belongs to the Special Issue Shape Memory Alloy (SMA) Actuators and Their Applications)
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<p>Illustration of the human finger movement mechanism and various joint structures.</p>
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<p>(<b>a</b>) Fabricated exoskeleton glove, (<b>b</b>) Control and power system, (<b>c</b>–<b>e</b>) Various end effectors designed for the treatment of the MCP, PIP, and DIP joints, respectively.</p>
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<p>Linkage mechanism: (<b>a</b>) Side view, (<b>b</b>) Four-bar model, (<b>c</b>) Hollow disks friction model.</p>
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<p>Schematic representation of the Simulink system model.</p>
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<p>Measurement apparatus for evaluating dynamic finger movements.</p>
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<p>(<b>a</b>) Schematic depiction of the Grip Sensor and test objects, (<b>b</b>) Calibration results.</p>
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<p>Comparison of simulation and experimental test for a profile input.</p>
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<p>Stress–temperature phase diagrams for NiTi shape memory alloy wire: (<b>a</b>) Under different constant DC voltage stimulation, (<b>b</b>) Under PWM stimulation signals. The color legend indicates the martensite volume fraction.</p>
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<p>Experimental results of finger movement measurements at different input speeds, with transparent margins indicating the measurement error bands.</p>
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<p>Experimental results of the joint displacements for all fingers: (<b>a</b>) Metacarpophalangeal (MCP) joint, (<b>b</b>) Proximal Interphalangeal (PIP) joint, and (<b>c</b>) Distal Interphalangeal/Interphalangeal (DIP/IP) joint.</p>
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<p>Experimental results of the torque measurement for all fingers: (<b>a</b>) Metacarpophalangeal (MCP) joint; (<b>b</b>) Proximal Interphalangeal (PIP) joint, and (<b>c</b>) Distal Interphalangeal/Interphalangeal (DIP/IP) joint.</p>
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31 pages, 25262 KiB  
Article
Optimal Design of a Bilateral Stand-Alone Robotic Motion-Assisted Finger Exoskeleton for Home Rehabilitation
by Tony Punnoose Valayil and Tanio K. Tanev
Machines 2024, 12(10), 685; https://doi.org/10.3390/machines12100685 - 29 Sep 2024
Viewed by 792
Abstract
This paper presents a novel exoskeleton robot that can be used at home to rehabilitate the index fingers of stroke-affected patients. This exoskeleton is designed as a one-degree-of-freedom four-bar mechanism able to guide the human index finger to perform a finger curl exercise [...] Read more.
This paper presents a novel exoskeleton robot that can be used at home to rehabilitate the index fingers of stroke-affected patients. This exoskeleton is designed as a one-degree-of-freedom four-bar mechanism able to guide the human index finger to perform a finger curl exercise motion. The proposed device is the only lateral, stand-alone mechanism built to date that can carry the weight of the human hand, thus making the user free from wearing it. The design starts by tracing the trajectory of the index finger using ‘Angulus’ software. ‘SALAR Mechanism Synthesizer’ software is used for dimensional synthesis of the four-bar mechanism. Using additive manufacturing technology, a prototype of the proposed device is developed. Static force analysis is performed to select the most appropriate actuator for producing the required torque to manipulate the fingers effectively. The kinematics of the index finger while performing a finger curl exercise is obtained. The proposed linkage mechanism can drive the index fingers of both hands. Simulation and experimental results proved the feasibility and effectiveness of the proposed design to be used for index finger rehabilitation for a wide range of users and applications by making simple minor alterations in the design. Also, a scheme for when the device can be used for rehabilitating the middle finger together with the index finger when performing flexion and extension motions is discussed. Full article
(This article belongs to the Section Robotics, Mechatronics and Intelligent Machines)
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<p>Anatomy of the human hand.</p>
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<p>Flexion/extension motions performed by the index finger.</p>
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<p>(<b>a</b>) Finger Curl exercise for stroke patients, (<b>b</b>) Four-bar mechanism attached to the lateral side of the finger.</p>
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<p>Joint angles measured during finger curl exercise (<b>a</b>–<b>c</b>) Joint angles measured at first position, (<b>d</b>–<b>f</b>) Joint angles measured at second position, (<b>g</b>–<b>i</b>) Joint angles measured at third position.</p>
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<p>Kinematic model of the human index finger.</p>
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<p>(<b>a</b>) Workspace of the index finger, (<b>b</b>) Fingertip positions.</p>
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<p>(<b>a</b>) Trajectory of the mechanism, (<b>b</b>) End-effector position.</p>
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<p>Results obtained using FMinCon optimization setup in SALAR.</p>
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<p>CAD model of the robot.</p>
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<p>Snapshots during the motion (<b>a</b>) developed prototype connected to a computer using Arduino board (<b>b</b>) coupler at position 1 (<b>c</b>) coupler at position 2 and (<b>d</b>) coupler at position 3.</p>
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<p>(<b>a</b>) Coupler for left-hand index finger and right-hand index finger when performing finger curl exercise. (<b>b</b>) Coupler for middle finger and index finger when performing flexion and extension motions.</p>
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<p>Dummy index finger.</p>
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<p>Design parameters for finger insert: (<b>a</b>) 5 mm width and no inclination, (<b>b</b>) 3 mm width and no inclination, (<b>c</b>) 3 mm width and 20° inclination, (<b>d</b>) 3 mm width and 45° inclinations.</p>
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<p>Robotic-fingered exoskeleton performing index finger rehabilitation.</p>
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<p>Schematic of four-bar mechanism for static force analysis.</p>
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<p>Torque variation during the motion of the mechanism.</p>
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<p>Torque variation versus the input angle <span class="html-italic">θ</span> and angle α.</p>
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<p>Change in threshold values.</p>
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19 pages, 11852 KiB  
Article
Thermal Monitoring of an Internal Combustion Engine for Lightweight Fixed-Wing UAV Integrating PSO-Based Modelling with Condition-Based Extended Kalman Filter
by Aleksander Suti, Gianpietro Di Rito and Giuseppe Mattei
Drones 2024, 8(10), 531; https://doi.org/10.3390/drones8100531 - 29 Sep 2024
Viewed by 358
Abstract
The internal combustion engines of long-endurance UAVs are optimized for cruises, so they are prone to overheating during climbs, when power requests increase. To counteract the phenomenon, step-climb maneuvering is typically operated, but the intermittent high-power requests generate repeated heating–cooling cycles, which, over [...] Read more.
The internal combustion engines of long-endurance UAVs are optimized for cruises, so they are prone to overheating during climbs, when power requests increase. To counteract the phenomenon, step-climb maneuvering is typically operated, but the intermittent high-power requests generate repeated heating–cooling cycles, which, over multiple missions, may promote thermal fatigue, performance degradation, and failure. This paper deals with the development of a model-based monitoring of the cylinder head temperature of the two-stroke engine employed in a lightweight fixed-wing long-endurance UAV, which combines a 0D thermal model derived from physical first principles with an extended Kalman filter capable to estimate the head temperature under degraded conditions. The parameters of the dynamic model, referred to as nominal condition, are defined through a particle-swarm optimization, minimizing the mean square temperature error between simulated and experimental flight data (obtaining mean and peak errors lower than 3% and 10%, respectively). The validated model is used in a so-called condition-based extended Kalman filter, which differs from a conventional one for a correction term in section prediction, leveraged as degradation symptom, based on the deviation of the model-state derivative with respect to the actual measurement. The monitoring algorithm, being executable in real-time and capable of identifying incipient degradations of the thermal flow, demonstrates applicability for online diagnostics and predictive maintenance purposes. Full article
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<p>UAV Rapier X-25, manufactured by Sky Eye Systems (Foligno, Italy).</p>
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<p>Schematic of the reference propulsion system.</p>
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<p>Thermal flows in the combustion chamber: (<b>a</b>) reference scheme of heat transfer from the chamber walls to environment; (<b>b</b>) in-cylinder thermodynamic process.</p>
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<p>CBEKF block diagram.</p>
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<p>Example of a measurement quantization (<span class="html-italic">b</span> = 0.5) with raw and sigmoid-based transition at <span class="html-italic">a</span> = 100 (<b>top</b>) and measurement sigmoid-based derivative with respect to state (<b>bottom</b>).</p>
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<p>Experimental and simulated CHT time histories: (<b>a</b>) FM1, (<b>b</b>) FM2, (<b>c</b>) errors.</p>
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<p>CHT estimation with degradation injection (DI) at <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>Q</mi> </mrow> </msub> <mo>=</mo> <mn>1.1</mn> <mo>,</mo> <mtext> </mtext> <msub> <mrow> <mtext> </mtext> <mi>γ</mi> </mrow> <mrow> <mi>D</mi> </mrow> </msub> <mo>=</mo> <mn>1</mn> </mrow> </semantics></math>: (<b>a</b>) whole time history; (<b>b</b>) detail on nominal conditions regime; (<b>c</b>) detail on degraded conditions regime.</p>
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<p>CHT estimation with degradation injection (DI) at <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>Q</mi> </mrow> </msub> <mo>=</mo> <mn>1.5</mn> <mo>,</mo> <mtext> </mtext> <msub> <mrow> <mtext> </mtext> <mi>γ</mi> </mrow> <mrow> <mi>D</mi> </mrow> </msub> <mo>=</mo> <mn>1</mn> </mrow> </semantics></math>: (<b>a</b>) whole time history; (<b>b</b>) detail on nominal conditions regime; (<b>c</b>) detail on degraded conditions regime.</p>
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<p>Estimation error with CBEKF-AU strategy at increasing values of <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>Q</mi> </mrow> </msub> </mrow> </semantics></math> (<math display="inline"><semantics> <mrow> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>D</mi> </mrow> </msub> <mo>=</mo> <mn>1</mn> </mrow> </semantics></math>).</p>
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<p>Model-deviation term with degradation injection (DI) at <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>Q</mi> </mrow> </msub> <mo>=</mo> <mn>1.1</mn> <mtext> </mtext> <mfenced separators="|"> <mrow> <mi>s</mi> <mi>o</mi> <mi>l</mi> <mi>i</mi> <mi>d</mi> <mtext> </mtext> <mi>l</mi> <mi>i</mi> <mi>n</mi> <mi>e</mi> </mrow> </mfenced> <mo> </mo> <mi mathvariant="normal">a</mi> <mi mathvariant="normal">n</mi> <mi mathvariant="normal">d</mi> <mo> </mo> <msub> <mrow> <mi>γ</mi> </mrow> <mrow> <mi>Q</mi> </mrow> </msub> <mo>=</mo> <mn>1.5</mn> <mtext> </mtext> <mfenced separators="|"> <mrow> <mi>d</mi> <mi>o</mi> <mi>t</mi> <mi>t</mi> <mi>e</mi> <mi>d</mi> <mtext> </mtext> <mi>l</mi> <mi>i</mi> <mi>n</mi> <mi>e</mi> </mrow> </mfenced> <mo>,</mo> <mo> </mo> <msub> <mrow> <mo stretchy="false">(</mo> <mi>γ</mi> </mrow> <mrow> <mi>D</mi> </mrow> </msub> <mo>=</mo> <mn>1</mn> <mo stretchy="false">)</mo> </mrow> </semantics></math>.</p>
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<p>Model-deviation term derivative 10 s after the degradation injection.</p>
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<p>Flight measurements during FM1 and FM2: (<b>a</b>) throttle position; (<b>b</b>) ICE angular speed.</p>
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<p>Flight measurements during FM1 and FM2: (<b>a</b>) altitude; (<b>b</b>) calibrated airspeed.</p>
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<p>Flight measurements during FM1 and FM2: (<b>a</b>) CHT; (<b>b</b>) outside air temperature.</p>
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<p>Heat-generated power at sea level as a function of throttle position and angular speed.</p>
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<p>PSO cost function (blue line) and elapsed time per iteration (red line).</p>
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17 pages, 6478 KiB  
Article
Investigation of Innovative High-Response Piezoelectric Actuator Used as Smart Actuator–Sensor System
by Marko Šimic and Niko Herakovič
Appl. Sci. 2024, 14(18), 8523; https://doi.org/10.3390/app14188523 - 22 Sep 2024
Viewed by 781
Abstract
This paper presents an experimental analysis of a high-response piezoelectric actuator system for the modular design of hydraulic digital fluid control units. It focuses on determining static and dynamic characteristics, forming the basis for developing a smart Industry 4.0 component that incorporates both [...] Read more.
This paper presents an experimental analysis of a high-response piezoelectric actuator system for the modular design of hydraulic digital fluid control units. It focuses on determining static and dynamic characteristics, forming the basis for developing a smart Industry 4.0 component that incorporates both actuator and sensor function. The design process examines the main challenges, advantages, disadvantages, and working principles to define parameters that impact the actuator’s behaviour and performance. The new piezoelectric actuator system features three piezoelectric stack actuators in series, enabling simultaneous actuation and sensing by applying and measuring the electrical voltage at each piezo element. The experimental setup and test methodology are explained in detail, revealing that the new design, combined with an appropriate open-loop or closed-loop control method, offers superior actuator stroke control, high stroke resolution, and a high-dynamic step response. This paper proposes a concept of a smart piezo actuator system focused on I4.0 and an actuator administration shell, integrated with 5G and RFID technology, which will allow automatic plug-and-play functionality and efficient interconnection, communication, and data transfer between the hydraulic valve and the piezoelectric actuator system. Full article
(This article belongs to the Special Issue Research Progress on Hydraulic Fluid and Hydraulic Systems)
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<p>Real picture of linear multilayer piezoelectric stack actuator (<b>a</b>) and operational principles (<b>b</b>).</p>
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<p>Force–displacement curve for a piezoelectric stack actuator.</p>
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<p>Effect of a spring preload on a piezoelectric stack actuator.</p>
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<p>Concept of piezoelectric actuator system (<b>a</b>), cross-section view of serial-connected piezo elements (PE) (<b>b</b>), and real picture of piezoelectric actuator system (<b>c</b>).</p>
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<p>Theoretical stroke of piezo actuator system considering the disc spring stiffness.</p>
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<p>Scheme of experimental setup and measured voltage at each PE.</p>
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<p>Real picture of experimental test rig.</p>
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<p>Control scenarios. one active PE (<b>a</b>), two active PEs (<b>b</b>) and three active PEs (<b>c</b>).</p>
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<p>Step response of a second-order system.</p>
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<p>Maximum stroke of piezoelectric actuator system vs. active PE.</p>
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<p>Electrical voltage measured on an individual PE when activating PE3 (<b>a</b>), PE2 (<b>b</b>), PE1 (<b>c</b>), PE2 and PE3 (<b>d</b>), PE1 and PE3 (<b>e</b>), PE1 and PE2 (<b>f</b>), and PE1, PE2, and PE3 (<b>g</b>).</p>
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<p>Discrete values of PE stroke achieved with the PWM control strategy (<b>a</b>) and a control signal of 0.1 ms to achieve a 20 μm piezo electric actuator stroke (<b>b</b>).</p>
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<p>The step response of the piezoelectric actuator system depended on active PEs.</p>
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<p>Step response of the piezoelectric actuator system with one PE using PWM control. Overview with varying PWM signal widths (<b>a</b>) and detailed view with a 20 µs PWM signal (<b>b</b>).</p>
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<p>Improved step response of the piezoelectric actuator system.</p>
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<p>The concept of smart piezoelectric actuators used in hydraulic on/off valves and the integrated Asset Administration Shell.</p>
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11 pages, 582 KiB  
Protocol
Effects of Home-Based Daily Respiratory Muscle Training on Swallowing Outcomes in Patients with Chronic Stroke: Protocol for a Randomized Controlled Trial
by Mónica Zapata-Soria, Irene Cabrera-Martos, Alejandro Heredia-Ciuró, Esther Prados-Román, Javier Martín-Nuñez and Marie Carmen Valenza
J. Clin. Med. 2024, 13(18), 5547; https://doi.org/10.3390/jcm13185547 - 19 Sep 2024
Viewed by 556
Abstract
(1) Background: Swallowing disorders are common following a stroke. This study aims to evaluate the effects of a home-based daily intervention focused on inspiratory and expiratory muscle training on swallowing outcomes in patients with chronic stroke. (2) Methods: This manuscript presents the protocol [...] Read more.
(1) Background: Swallowing disorders are common following a stroke. This study aims to evaluate the effects of a home-based daily intervention focused on inspiratory and expiratory muscle training on swallowing outcomes in patients with chronic stroke. (2) Methods: This manuscript presents the protocol of a single-blind randomized clinical trial. Patients with chronic stroke will be randomly assigned to either an experimental or a control group. The experimental group will undergo daily home-based respiratory muscle training in addition to standard speech and language therapy, while the control group will receive only the standard intervention. The main outcome measures will include the aspiration risk, the strength of respiratory muscles, and peak cough flow. (3) Results: It is hypothesized that patients receiving home-based respiratory training in addition to standard therapy will achieve significant improvements in aspiration risk, respiratory muscle strength, and cough efficacy in comparison with those included in the control group. The results will be published as a manuscript. (4) Conclusions: This study aims to provide evidence on the effectiveness of home-based respiratory muscle training in enhancing swallowing function and respiratory parameters in patients with chronic stroke. Full article
(This article belongs to the Section Clinical Rehabilitation)
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<p>Protocol of the home-based respiratory muscle training and standard speech and language interventions.</p>
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25 pages, 6749 KiB  
Article
Application of Artificial Neuromolecular System in Robotic Arm Control to Assist Progressive Rehabilitation for Upper Extremity Stroke Patients
by Jong-Chen Chen and Hao-Ming Cheng
Actuators 2024, 13(9), 362; https://doi.org/10.3390/act13090362 - 16 Sep 2024
Viewed by 591
Abstract
Freedom of movement of the hands is the most desired hope of stroke patients. However, stroke recovery is a long, long road for many patients. If artificial intelligence can assist human arm movement, the possibility of stroke patients returning to normal hand movement [...] Read more.
Freedom of movement of the hands is the most desired hope of stroke patients. However, stroke recovery is a long, long road for many patients. If artificial intelligence can assist human arm movement, the possibility of stroke patients returning to normal hand movement might be significantly increased. This study uses the artificial neuromolecular system (ANM system) developed in our laboratory as the core of motion control, in an attempt to learn to control the mechanical arm to produce actions similar to human rehabilitation training and the transition between different activities. This research adopts two methods. The first is hypothetical exploration, the so-called “artificial world” simulation method. The detailed approach uses the V-REP (Virtual Robot Experimentation Platform) to conduct different experimental runs to capture relevant data. Our policy is to establish an action database systematically to a certain extent. From these data, we use the ANM system with self-organization and learning capabilities to develop the relationship between these actions and establish the possibility of conversion between different activities. The second method of this study is to use the data from a hospital in Toronto, Canada. Our experimental results show that the ANM system can continuously learn for problem-solving. In addition, our three experimental results of adaptive learning, transfer learning, and cross-task learning further confirm that the ANM system can use previously learned systems to complete the delivered tasks through autonomous learning (instead of learning from scratch). Full article
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<p>The structure of the ANM system.</p>
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<p>Cytoskeleton elements.</p>
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<p>Evolutionary learning of the ANM system.</p>
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<p>Research model.</p>
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<p>Comparison of muscle joints between robotic arm and human arm.</p>
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<p>Artificial World dataset data collection flowchart.</p>
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<p>(<b>a</b>) Microsoft Kinect (k4w) v2. (<b>b</b>) A handheld end-effector with two degrees of freedom.</p>
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<p>Comparison of learning results at different stages of the ANM system.</p>
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<p>The structure of adaptive learning.</p>
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<p>The relationship between healthy people and patients in the Toronto Rehabilitation dataset.</p>
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<p>The concept of clustering in adaptive learning.</p>
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<p>(<b>a</b>) Clustering results of ten healthy people moving forward–backward with left arm. (<b>b</b>) Clustering results of nine healthy people moving forward–backward with right arm. (<b>c</b>) Clustering results of ten healthy people moving side-to-side with left arm. (<b>d</b>) Clustering results of nine healthy people moving side-to-side with right arm.</p>
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<p>(<b>a</b>) Similarity clustering of ten healthy people’s compensatory actions (Fwr_Bck_L) for P4. (<b>b</b>) Similarity clustering of nine healthy people’s compensatory actions (Fwr_Bck_R) for P4. (<b>c</b>) Similarity clustering of ten healthy people’s compensatory actions (Sd2Sd_Bck_L) for P4. (<b>d</b>) Similarity clustering of nine healthy people’s compensatory actions (Sd2Sd_Bck_R) for P4. We note that different colors of lines are for better visualization.</p>
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<p>Comparative diagram of adaptive and progressive learning in rehabilitation.</p>
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<p>The concept of progressive learning.</p>
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12 pages, 4905 KiB  
Article
Research on the Magnetorheological Finishing Technology of a High-Steepness Optical Element Based on the Virtual-Axis and Spiral Scanning Path
by Chihao Chen, Chaoliang Guan, Meng Liu, Yifan Dai and Hao Hu
Micromachines 2024, 15(9), 1154; https://doi.org/10.3390/mi15091154 - 15 Sep 2024
Viewed by 615
Abstract
Magnetorheological finishing (MRF) of aspherical optical elements usually requires the coordination between the translational axes and the oscillating axes of the machine tool to realize the processing. For aspheric optical elements whose steepness exceeds the machining stroke of the equipment, there is still [...] Read more.
Magnetorheological finishing (MRF) of aspherical optical elements usually requires the coordination between the translational axes and the oscillating axes of the machine tool to realize the processing. For aspheric optical elements whose steepness exceeds the machining stroke of the equipment, there is still no better method to achieve high-precision and high-efficiency error convergence. To solve this problem, an MRF method combining virtual-axis technology and a spiral scanning path is proposed in this paper. Firstly, the distribution law of the magnetic induction intensity inside the polishing wheel is analyzed by simulation, the stability of the removal efficiency of the removal function within the ±7 angle of the normal angle of the polishing wheel is determined, and MRF is expanded from traditional single-point processing to circular arc segment processing. Secondly, the spiral scanning path is proposed for aspherical rotational symmetric optical elements, which can reduce the requirements of the number of machine tool axes and the dynamic performance of machine tools. Finally, an aspherical fused silica optical element with a curvature radius of 400 mm, K value of −1, and aperture of 100 mm is processed. The PV value of this optical element converges from 189.2 nm to 24.85 nm, and the RMS value converges from 24.85 nm to 5.74 nm. The experimental results show that the proposed combined process has the ability to modify curved optical elements and can be applied to ultra-precision machining of high-steepness optical elements. Full article
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<p>(<b>a</b>) Traditional machining. (<b>b</b>) Spiral scanning path. (<b>c</b>) Raster scanning path.</p>
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<p>Virtual-axis technology.</p>
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<p>Electromagnet generator body part.</p>
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<p>Magnetic induction intensity distribution.</p>
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<p>Magnetic induction intensity change curve.</p>
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<p>Inverted D shape.</p>
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<p>Geometric shape. (<b>a</b>) Removal function of 0<sup>∘</sup> angle, (<b>b</b>–<b>h</b>) removal function of 1<sup>∘</sup>∼7<sup>∘</sup> angle, and (<b>i</b>–<b>o</b>) −1<sup>∘</sup>∼−7<sup>∘</sup>.</p>
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<p>One dimensional Fourier amplitude spectrum normalization curve.</p>
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<p>Self-developed MRF machine tool (KDUPF650-7).</p>
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<p>Surface error distribution before and after machining: (<b>a</b>) before processing and (<b>b</b>) after processing.</p>
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<p>Roughness before and after machining: (<b>a</b>) before processing and (<b>b</b>) after processing.</p>
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18 pages, 3188 KiB  
Article
Intelligent Control System for Brain-Controlled Mobile Robot Using Self-Learning Neuro-Fuzzy Approach
by Zahid Razzaq, Nihad Brahimi, Hafiz Zia Ur Rehman and Zeashan Hameed Khan
Sensors 2024, 24(18), 5875; https://doi.org/10.3390/s24185875 - 10 Sep 2024
Viewed by 615
Abstract
Brain-computer interface (BCI) provides direct communication and control between the human brain and physical devices. It is achieved by converting EEG signals into control commands. Such interfaces have significantly improved the lives of disabled individuals suffering from neurological disorders—such as stroke, amyotrophic lateral [...] Read more.
Brain-computer interface (BCI) provides direct communication and control between the human brain and physical devices. It is achieved by converting EEG signals into control commands. Such interfaces have significantly improved the lives of disabled individuals suffering from neurological disorders—such as stroke, amyotrophic lateral sclerosis (ALS), and spinal cord injury—by extending their movement range and thereby promoting self-independence. Brain-controlled mobile robots, however, often face challenges in safety and control performance due to the inherent limitations of BCIs. This paper proposes a shared control scheme for brain-controlled mobile robots by utilizing fuzzy logic to enhance safety, control performance, and robustness. The proposed scheme is developed by combining a self-learning neuro-fuzzy (SLNF) controller with an obstacle avoidance controller (OAC). The SLNF controller robustly tracks the user’s intentions, and the OAC ensures the safety of the mobile robot following the BCI commands. Furthermore, SLNF is a model-free controller that can learn as well as update its parameters online, diminishing the effect of disturbances. The experimental results prove the efficacy and robustness of the proposed SLNF controller including a higher task completion rate of 94.29% (compared to 79.29%, and 92.86% for Direct BCI and Fuzzy-PID, respectively), a shorter average task completion time of 85.31 s (compared to 92.01 s and 86.16 s for Direct BCI and Fuzzy-PID, respectively), and reduced settling time and overshoot. Full article
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<p>Schematic of the proposed methodology for an EEG controlled mobile robot. The BCI system translates human intentions into steering commands. The shared control system manages automatic switching between user input and autonomous navigation, following <math display="inline"><semantics> <msub> <mi mathvariant="italic">Rule</mi> <mi>X</mi> </msub> </semantics></math> to ensure safety. The robotics system communicates the robot’s states and surrounding information among different controller nodes.</p>
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<p>Schematic of the wheeled mobile robot showing a two-dimensional coordinate system with the <math display="inline"><semantics> <mrow> <mi>x</mi> <mo>−</mo> <mi>o</mi> <mo>−</mo> <mi>y</mi> </mrow> </semantics></math> global frame and the <math display="inline"><semantics> <mrow> <msub> <mi>x</mi> <mi>c</mi> </msub> <mo>−</mo> <mi>B</mi> <mo>−</mo> <msub> <mi>y</mi> <mi>c</mi> </msub> </mrow> </semantics></math> local frame of the robot. G represents the center of gravity of the robot. The distance between the wheels is <math display="inline"><semantics> <mrow> <mn>2</mn> <mi>R</mi> </mrow> </semantics></math>, and the diameter of each wheel is <math display="inline"><semantics> <mrow> <mn>2</mn> <mi>r</mi> </mrow> </semantics></math>. <math display="inline"><semantics> <mi>ω</mi> </semantics></math> and <span class="html-italic">u</span> represent the angular and linear velocities of the robot, respectively. The angle <math display="inline"><semantics> <mi>ϕ</mi> </semantics></math> indicates the rotation between the global and local frames.</p>
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<p>Framework of the self−learning neuro−fuzzy control scheme. The reference model filters the desired changes in the plant’s output (w), guiding the plant to follow the set−point trajectory (<span class="html-italic">r</span>). The proportional feedback controller (with <math display="inline"><semantics> <msub> <mi>k</mi> <mi>p</mi> </msub> </semantics></math> gain) minimizes the impact of unmeasured disturbances. The feedback error learning module estimates the correct control signal (<math display="inline"><semantics> <msub> <mover accent="true"> <mi>u</mi> <mo stretchy="false">˜</mo> </mover> <mi>f</mi> </msub> </semantics></math>), while the fuzzy identification scheme updates the controller parameters (ŵ). The feedforward controller (neuro−fuzzy model) approximates the inverse model of a nonlinear plant when properly trained.</p>
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<p>Structure of Obstacle Avoidance Controller (OAC). IT2FLS processes three LIDAR distance inputs, fuzzifies them into IT2 fuzzy sets, and applies inference rules. The type reducer converts these to IT1 fuzzy sets, and the defuzzifier computes the angular velocity for robot control.</p>
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<p>The membership functions of AOC for (<b>a</b>) input variables and (<b>b</b>) output variables; Note: LOD = FOD = ROD.</p>
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<p>Online simulation setup of a robotic system where a user maneuvers the mobile robot using EEG signals to targets A or B, avoiding obstacles.</p>
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<p>Experimental scenario. The subject focuses on the SSVEP visual stimuli (left screen) to maneuver the robot through obstacles (right screen) and reach the target safely.</p>
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<p>Comparison of system performance among the Direct BCI, Fuzzy-PID, and SLNF controllers for (<b>a</b>) Task completion rate (%) and (<b>b</b>) Task completion time (seconds). The SLNF controller achieved a higher average task completion rate of 94.29% (vs. 79.29% for Direct BCI and 92.86% for Fuzzy-PID) and a shorter average task completion time of 85.31 s (vs. 92.01 s for Direct BCI and 86.16 s for Fuzzy-PID). Statistically significant differences are indicated with (*) for <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Robot trajectories produced by Subject Three using (<b>a</b>) the proposed SLNF controller and (<b>b</b>) Direct BCI control. The trajectories with the proposed SLNF controller show no collisions, demonstrating the efficacy of OAC, while Direct BCI control method was unable to handle obstacle avoidance.</p>
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<p>Step input disturbance torque signals. These test the disturbance handling capability of our proposed control system.</p>
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<p>Disturbance rejection comparison among Direct BCI control, fuzzy-PID, and the proposed controller for (<b>a</b>) linear velocity and (<b>b</b>) angular velocity. Initially, the SLNF controller exhibits the highest overshoot in linear velocity but reduces it over time due to its online learning capability, as shown in the zoomed area. For angular velocity, the SLNF controller shows minimal overshoot and settling time, with disturbance effects decreasing over time. Direct BCI and Fuzzy-PID controllers do not show a significant reduction in disturbance.</p>
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23 pages, 2695 KiB  
Review
Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition
by Patrycja Marzęta-Assas, Damian Jacenik and Zbigniew Zasłona
Int. J. Mol. Sci. 2024, 25(18), 9782; https://doi.org/10.3390/ijms25189782 - 10 Sep 2024
Viewed by 1135
Abstract
Arginases are key enzymes that hydrolyze L-arginine to urea and L-ornithine in the urea cycle. The two arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), regulate the proliferation of cancer cells, migration, and apoptosis; affect immunosuppression; and promote the synthesis of polyamines, [...] Read more.
Arginases are key enzymes that hydrolyze L-arginine to urea and L-ornithine in the urea cycle. The two arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), regulate the proliferation of cancer cells, migration, and apoptosis; affect immunosuppression; and promote the synthesis of polyamines, leading to the development of cancer. Arginases also compete with nitric oxide synthase (NOS) for L-arginine, and their participation has also been confirmed in cardiovascular diseases, stroke, and inflammation. Due to the fact that arginases play a crucial role in the development of various types of diseases, finding an appropriate candidate to inhibit the activity of these enzymes would be beneficial for the therapy of many human diseases. In this review, based on numerous experimental, preclinical, and clinical studies, we provide a comprehensive overview of the biological and physiological functions of ARG1 and ARG2, their molecular mechanisms of action, and affected metabolic pathways. We summarize the recent clinical trials’ advances in targeting arginases and describe potential future drugs. Full article
(This article belongs to the Section Molecular Oncology)
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<p>Cellular and molecular consequences of the imbalance of NO and L-arginine action in cancer. NOS metabolizes L-arginine to generate both L-citrulline and NO. At high NO concentrations, cellular apoptosis, oxidative stress, DNA damage, and cellular toxicity occur. Moderate and low amounts of NO prevent cells from apoptosis through the ERK, mTOR, and AT signaling pathways, and they promote the development of cancers and the invasion of cancer cells. Arginases hydrolyze L-arginine to generate L-ornithine and urea. In the reaction catalyzed by OAT, L-ornithine is transformed to L-proline and glutamate. ODC catalyzes the reaction of polyamine generation from L-ornithine. L-proline participates in the production of collagen. In the case of cancer, the balance between NO and L-arginine is disturbed. There is increased arginase activity, which depletes L-arginine to a greater extent, causing reduced NO production and thus increasing L-ornithine levels. Then, L-ornithine catalyzed by OAT and ODC increases the proline, glutamate, and, most importantly, polyamine generation. In this way, cancer cell migration, invasion, and proliferation occur. Because the NO level is low, there is no cellular apoptosis by the AKT, ERK, and mTOR pathways but further proliferation of these cells. OAT, ornithine aminotransferase; NOS, nitric oxide synthase; ARG, arginase; ODC, ornithine decarboxylase; NO, nitric oxide; AKT, protein kinase B; CAT, cationic amino acid transporter; mTOR, mammalian target of rapamycin; ERK, extracellular signal-regulated kinase; NPCs, neural progenitor cells.</p>
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<p>The role of arginase in cancer metabolism. In the urea cycle, the carbonyl group of citrulline, together with the amino group of aspartate, forms argininosuccinate in a condensation reaction. This reaction is catalyzed by ASS and is ATP-dependent. Argininosuccinate is then cleaved by ASL to form fumarate and arginine. Arginine and glycine in the urea cycle are catalyzed by glycine amidinotransferase AGAT (EC 2.1.4.1) to produce glycocyamine, which is further methylated to creatinine by guanidinoacetate methyltransferase GAMT (EC 2.1.1.2). Arginine in the urea cycle is also cleaved by ARG to ornithine and urea, and by NOS to NO and citrulline. Ornithine is necessary for the further synthesis of polyamines, proline, and glutamate by ODC and OAT synthases, respectively. Ornithine is further transported back to the mitochondria where it is converted to citrulline by OTC to begin the urea cycle again. In the case of cancer, ARG1 and ARG2 become activated, so arginine is fully depleted. Arginine is not hydrolyzed by NOS, and, as a result, the amount of NO is reduced, which disturbs the synthesis of chemokines and pro-inflammatory cytokines responsible for the activation of T cells. Activated arginases lead to the increased production of ornithine, which is a direct substrate for the synthesis of polyamines, glutamate, and proline. This effect leads to increased protein biosynthesis and the proliferation and migration of cancer cells. ARG, arginase; ODC, ornithine decarboxylase; NOS, nitric oxide synthase; ASL (EC 4.3.2.1), argininosuccinate lyase; ASS, argininosuccinate synthase; OTC, ornithine transcarbamylase; OAT, ornithine aminotransferase; P5Cr (EC 1.5.1.2), P5C reductase; P5CS (EC 2.7.2.11), P5C synthase; P5C, Δ1-pyrroline-5-carboxylate; AGAT, glycine amidinotransferase; GAMT, guanidinoacetate methyltransferase, → direct path; −→ multistep path.</p>
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<p>OATD-02 inhibits intracellular ARG1 and ARG2. The ARG1/ARG2 inhibitor OATD-02 inhibits the activity of cytosolic ARG1 and mitochondrial ARG2 by preventing the degradation of arginine by arginase. Arginine can therefore use NOS to stimulate NO synthesis and the production of chemokines and pro-inflammatory cytokines, which leads to T cell activation and proliferation. The inhibition of both arginases causes reduced production of L-ornithine. ODC does not catalyze the decarboxylation of L-ornithine to form putrescine, a substrate necessary for the synthesis of polyamines, which translates into reduced polyamine generation, thus inhibiting further proliferation of cancer cells. Additionally, OAT does not catalyze the reaction of converting L-ornithine to 5PC, which translates into reduced proline and glutamate generation. ARG, arginase; ODC, ornithine decarboxylase; NOS, nitric oxide synthase; ASL, argininosuccinate lyase; ASS, argininosuccinate synthase; OTC, ornithine transcarbamylase; OAT, ornithine aminotransferase; P5Cr, P5C reductase; P5CS, P5C synthase; P5C, Δ1-pyrroline-5-carboxylate; AGAT, glycine amidinotransferase; GAMT, guanidinoacetate methyltransferase, → direct path; −→ multistep path.</p>
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14 pages, 2546 KiB  
Article
Differences in Acute Expression of Matrix Metalloproteinases-9, 3, and 2 Related to the Duration of Brain Ischemia and Tissue Plasminogen Activator Treatment in Experimental Stroke
by Dong Wang, Sofiyan Saleem, Ryan D. Sullivan, Tieqiang Zhao and Guy L. Reed
Int. J. Mol. Sci. 2024, 25(17), 9442; https://doi.org/10.3390/ijms25179442 - 30 Aug 2024
Viewed by 458
Abstract
Matrix metalloproteinases (MMPs) such as MMP-9, 3, and 2 degrade the cellular matrix and are believed to play a crucial role in ischemic stroke. We examined how the duration of ischemia (up to 4 h) and treatment with recombinant tissue plasminogen activator altered [...] Read more.
Matrix metalloproteinases (MMPs) such as MMP-9, 3, and 2 degrade the cellular matrix and are believed to play a crucial role in ischemic stroke. We examined how the duration of ischemia (up to 4 h) and treatment with recombinant tissue plasminogen activator altered the comparative expression of these MMPs in experimental ischemic stroke with reperfusion. Both prolonged ischemia and r-tPA treatment markedly increased MMP-9 expression in the ischemic hemisphere (all p < 0.0001). The duration of ischemia and r-tPA treatment also significantly increased MMP-2 expression (p < 0.01–0.001) in the ischemic hemisphere (p < 0.01) but to a lesser degree than MMP-9. In contrast, MMP-3 expression significantly decreased in the ischemic hemisphere (p < 0.001) with increasing duration of ischemia and r-tPA treatment (p < 0.05–0001). MMP-9 expression was prominent in the vascular compartment and leukocytes. MMP-2 expression was evident in the vascular compartment and MMP-3 in NeuN+ neurons. Prolonging the duration of ischemia (up to 4 h) before reperfusion increased brain hemorrhage, infarction, swelling, and neurologic disability in both saline-treated (control) and r-tPA-treated mice. MMP-9 and MMP-2 expression were significantly positively correlated with, and MMP-3 was significantly negatively correlated with, infarct volume, swelling, and brain hemorrhage. We conclude that in experimental ischemic stroke with reperfusion, the duration of ischemia and r-tPA treatment significantly altered MMP-9, 3, and 2 expression, ischemic brain injury, and neurological disability. Each MMP showed unique patterns of expression that are strongly correlated with the severity of brain infarction, swelling, and hemorrhage. In summary, in experimental ischemic stroke in male mice with reperfusion, the duration of ischemia, and r-tPA treatment significantly altered the immunofluorescent expression of MMP-9, 3, and 2, ischemic brain injury, and neurological disability. In this model, each MMP showed unique patterns of expression that were strongly correlated with the severity of brain infarction, swelling, and hemorrhage. Full article
(This article belongs to the Special Issue Inflammatory Biomarkers in Ischemic Stroke)
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<p>Time-dependent changes in the expression of MMP-9, -3, and -2 in the ischemic (stroke) hemispheres in mouse brains post stroke. The immunofluorescent images at higher magnification (20×, scale bar = 100 μm) in (<b>a</b>–<b>c</b>) are representative fields showing the expression of MMP-9, 3, and 2 (red) in the ischemic hemisphere at 24 h post stoke with various ischemic times, 1, 2, and 4 h, respectively. The corresponding graphs at the bottom (<b>d</b>–<b>f</b>) show the quantitation of MMP-9, 3, and 2 expression levels in stroke hemisphere in mice treated with saline (control, ctl) or r-tPA. Data represent means ± SEM. Differences between groups were assessed by one-way ANOVA. *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001 vs. ctl group at indicated time points. <span class="html-italic">n</span> = 4–6. <span class="html-italic">ns</span> = non-significant.</p>
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<p>Co-localization of MMP-9, -2, and -3 and various cellular markers. Double immunofluorescence staining experiments were conducted with MMP-9 and various cell markers. (<b>a</b>–<b>c</b>) MMP-9 and collagen IV or Ly6G or CD68 (originally 20×, scale bar = 50 μm), to show that MMP-9 was expressed in (<b>a</b>) the vascular compartments and inflammatory cells, such as (<b>b</b>) neutrophil and (<b>c</b>) macrophage. (<b>d</b>) MMP-2 and collagen IV (originally 40×, scale bar = 25 μm), to show that MMP-2 was expressed in the vascular compartments. (<b>e</b>) MMP-3 and NeuN (originally 10×, scale bar = 100 μm), to show a neuronal source of MMP-3 expression. Arrows indicate vascular location of MMP-9 (<b>a</b>) and cytoplasmic location of MMP-3 on neurons (<b>c</b>) respectively.</p>
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<p>Correlation between expression of MMPs and neuronal outcomes. (<b>a</b>,<b>d</b>,<b>g</b>) Correlation between MMP-9 expression levels in both ctl and r-tPA groups and (<b>a</b>) infarct volume, (<b>d</b>) swelling, and (<b>g</b>) hemorrhage. (<b>b</b>,<b>e</b>,<b>h</b>) Correlation between MMP-3 expression levels in both ctl and r-tPA groups and (<b>b</b>) infarct volume, (<b>e</b>) swelling, and (<b>h</b>) hemorrhage. (<b>c</b>,<b>f</b>,<b>i</b>) Correlation between MMP-2 expression levels in both ctl and r-tPA groups and (<b>c</b>) infarct volume, (<b>f</b>) swelling, and (<b>i</b>) hemorrhage. Data represent means ± SEM of <span class="html-italic">n</span> = 12–18 mice per group. Either Pearson or Spearman test was used when the variables were normally distributed or non-parametrically distributed.</p>
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<p>The effect of r-tPA and duration of ischemia on ischemic brain injury and neurobehavioral outcomes. Ischemia was induced by 7–0 monofilament occlusion of the middle cerebral artery for the indicated times, followed by reperfusion for 24 h after ischemia onset. Ischemia was confirmed by an ~80% drop in hemispheric blood by laser Doppler flowmetry. (<b>a</b>) The percentage of brain infarction, (<b>b</b>) brain swelling (percentage), (<b>c</b>) the percentage of brain hemorrhage area. Neurobehavioral disability and sensorimotor dysfunction were assessed at 24 h by (<b>d</b>) modified Bederson score and (<b>e</b>) Corner test. Data are represented as mean ± SEM. Differences were assessed by two-way ANOVA with the Holm–Sidak correction for multiple inferences. Ctl (<span class="html-italic">n</span> = 4–6) and r-tPA (<span class="html-italic">n</span> = 5–6) per group.</p>
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15 pages, 1568 KiB  
Article
Effects of Virtual Rehabilitation Training on Post-Stroke Executive and Praxis Skills and Depression Symptoms: A Quasi-Randomised Clinical Trial
by Rosaria De Luca, Antonio Gangemi, Maria Grazia Maggio, Mirjam Bonanno, Andrea Calderone, Vincenza Maura Mazzurco Masi, Carmela Rifici, Irene Cappadona, Maria Pagano, Davide Cardile, Giulia Maria Giuffrida, Augusto Ielo, Angelo Quartarone, Rocco Salvatore Calabrò and Francesco Corallo
Diagnostics 2024, 14(17), 1892; https://doi.org/10.3390/diagnostics14171892 - 28 Aug 2024
Viewed by 821
Abstract
Introduction: Apraxia is a neurological disorder that is common after a stroke and impairs the planning and execution of movements. In the rehabilitation field, virtual reality (VR) presents new opportunities and offers advantages to both rehabilitation teams and individuals with neurological conditions. Indeed, [...] Read more.
Introduction: Apraxia is a neurological disorder that is common after a stroke and impairs the planning and execution of movements. In the rehabilitation field, virtual reality (VR) presents new opportunities and offers advantages to both rehabilitation teams and individuals with neurological conditions. Indeed, VR can stimulate and improve cognitive reserve and abilities, including executive function, and enhance the patient’s emotional status. Aim: The objective of this research is to determine the effectiveness of VR in improving praxis skills and behavioural functioning in individuals with severe stroke. Methods: A total of 20 stroke patients were enrolled from February 2022 to March 2023 and divided by the order of their recruitment into two groups: the experimental group (EG: n = 10) received training to improve their praxis skills using VR whereas the control one (CG: n = 10) received the same amount of standard training. All patients underwent an evaluation using a psychometric battery that consisted of the Hamilton Rating Scale for Depression (HRS-D), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Spinnler and Tognoni test, and De Renzi and Faglioni test. Valuations were performed before rehabilitation (T0) and after its completion (T1). Results: Both groups demonstrated significant improvements post-intervention. The EG showed a greater enhancement in their MMSE scores (p = 0.002), and reductions in both ideomotor and constructive apraxia (p = 0.002 for both), compared to the CG. The VR-based training also resulted in significant improvements in their depression symptoms (HRSD scores improved, p = 0.012 in EG vs. p = 0.021 in CG). Conclusions: This pilot study suggests that VR could help reduce cognitive, constructive apraxia and ideomotor apraxia symptoms caused by stroke injury. Full article
(This article belongs to the Special Issue Rehabilitation Medicine: Diagnosis and Management)
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<p>Demographic data. (<b>A</b>) Age distribution between groups. (<b>B</b>) Sex distribution between groups. EG = Experimental Group; CG = Control Group.</p>
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<p>Scores progress over time. Experimental Group (EG); Control Group (CG); Mini Mental State Examination (MMSE); Frontal Assessment Battery (FAB); Hamilton Rating Scale for Depression (HRS-D).</p>
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<p>Scores pre- and post-Treatment. EG = Experimental Group; CG = Control Group.</p>
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11 pages, 1077 KiB  
Article
Efficacy of a Virtual Reality Rehabilitation Protocol Based on Art Therapy in Patients with Stroke: A Single-Blind Randomized Controlled Trial
by Gaetano Tieri, Marco Iosa, Antonio Fortini, Federica Aghilarre, Federico Gentili, Cristiano Rubeca, Tommaso Mastropietro, Gabriella Antonucci and Roberto De Giorgi
Brain Sci. 2024, 14(9), 863; https://doi.org/10.3390/brainsci14090863 - 27 Aug 2024
Viewed by 1040
Abstract
Background: Art therapy has a long history of applications in cognitive and motor rehabilitation. More recently, a growing body of scientific literature has highlighted the potential of virtual reality in neurorehabilitation, though it has focused more on the technology itself than on the [...] Read more.
Background: Art therapy has a long history of applications in cognitive and motor rehabilitation. More recently, a growing body of scientific literature has highlighted the potential of virtual reality in neurorehabilitation, though it has focused more on the technology itself than on the principles adopted in digital scenarios. Methods: This study is a single-blind randomized controlled trial conducted on 40 patients with stroke, comparing conventional therapy (physical therapy for the upper and lower limbs, for posture and balance, cognitive therapy, occupational therapy, speech therapy, and specific therapy for swallowing, bowel, and bladder dysfunctions) to a protocol in which the upper limb physical therapy was substituted with art therapy administered by means of virtual reality exploiting the so-called Michelangelo effect. Results: After 12 sessions, patients in the virtual art therapy group showed a significantly greater improvement in independence in activities of daily living, as assessed by the Barthel Index (interaction of time and group: p = 0.001). Significant differences were also found in terms of upper limb muscle strength (Manual Muscle Test, p < 0.01) and reduction in spasticity (Ashworth scale, p = 0.007) in favor of the experimental group. In the virtual art therapy group, the effectiveness of the intervention was significantly correlated with patient participation (Pittsburgh Rehabilitation Participation Scale: R = 0.41), patient satisfaction (R = 0.60), and the perceived utility of the intervention by the therapist (R = 0.43). Conclusions: These findings support the efficacy of virtual art therapy leveraging the Michelangelo effect. Further studies should also focus on cognitive domains that could benefit from this type of approach. Full article
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<p>The figure illustrates a virtual art therapy example. The <b>left panel</b> depicts a person wearing a VR headset and holding the Oculus controller in her right hand. The <b>right panel</b> presents the first-person perspective within the virtual environment, where the virtual canvas is occluded by white pixels. The green spherical brush (placed in the same position of the joystick grasped by the participant) is used to remove the white pixels, revealing the underlying image.</p>
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<p>Mean ± standard deviation of Barthel Index pre- and post-treatment for Experimental Group (EG, in blue) and Control Group (CG, in red).</p>
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<p>Box whiskers plot of Manual Muscle Score for shoulder abduction (blue bars), elbow flexion (green bars), and pinch (yellow bars) pre- and post-treatment for Experimental Group (EG, on the left) and Control Group (CG, on the right). The boxes represent the distance between 1st and 3rd quartiles and contain the medians (wide black lines), whereas the black whiskers represent 1.5 times the interquartile ranges, with values out of this range reported as circles.</p>
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17 pages, 7077 KiB  
Article
Focal Cerebral Ischemia Induces Expression of Glutaminyl Cyclase along with Downstream Molecular and Cellular Inflammatory Responses
by Corinna Höfling, Luise Ulrich, Sina Burghardt, Philippa Donkersloot, Michael Opitz, Stefanie Geissler, Stephan Schilling, Holger Cynis, Dominik Michalski and Steffen Roßner
Cells 2024, 13(17), 1412; https://doi.org/10.3390/cells13171412 - 23 Aug 2024
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Abstract
Glutaminyl cyclase (QC) and its isoenzyme (isoQC) catalyze the formation of N-terminal pyroglutamate (pGlu) from glutamine on a number of neuropeptides, peptide hormones and chemokines. Chemokines of the C-C ligand (CCL) motif family are known to contribute to inflammation in neurodegenerative conditions. Here, [...] Read more.
Glutaminyl cyclase (QC) and its isoenzyme (isoQC) catalyze the formation of N-terminal pyroglutamate (pGlu) from glutamine on a number of neuropeptides, peptide hormones and chemokines. Chemokines of the C-C ligand (CCL) motif family are known to contribute to inflammation in neurodegenerative conditions. Here, we used a model of transient focal cerebral ischemia to explore functional, cellular and molecular responses to ischemia in mice lacking genes for QC, isoQC and their substrate CCL2. Mice of the different genotypes were evaluated for functional consequences of stroke, infarct volume, activation of glia cells, and for QC, isoQC and CCL2 expression. The number of QC-immunoreactive, but not of isoQC-immunoreactive, neurons increased robustly in the infarct area at 24 and 72 h after ischemia. In parallel, immunohistochemical signals for the QC substrate CCL2 increased from 24 to 72 h after ischemia induction without differences between genotypes analyzed. The increase in CCL2 was accompanied by morphological activation of Iba1-immunoreactive microglia and recruitment of MHC-II-positive cells at 72 h after ischemia. Among other chemokines quantified in the brain tissue, CCL17 showed higher concentrations at 72 h compared to 24 h after ischemia. Collectively, these data suggest a critical role for QC in inflammatory processes in the stroke-affected brain. Full article
(This article belongs to the Section Cells of the Nervous System)
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Graphical abstract

Graphical abstract
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<p>Characterization of focal cerebral ischemia in knock-out mouse models. Mice of different genotypes (wild-type, CCL2 KO, QC KO and isoQC KO) were subjected to transient focal cerebral ischemia for 30 min, followed by 24 h and 72 h observation periods. (<b>A</b>) Survival rate (<span class="html-italic">p</span> = 0.858), Menzies score (<span class="html-italic">p</span> = 0.91), overall physical condition (<span class="html-italic">p</span> = 0.82) and body weight (<span class="html-italic">p</span> = 0.78) did not differ significantly between genotypes. Only 45% (wild type) to 58% (QC KO) of the animals subjected to the operation procedure survived for 72 h. For all genotypes, a constant Menzies score of 3 was determined at all time points. In contrast, the overall physical condition steadily declined (higher scores indicating worse condition) during the 72 h post-surgery period, which was also characterized by a weight loss ranging between 7% in wild-type mice and 16% in isoQC KO mice. (<b>B</b>) Immunohistochemical NeuN + HuC/D images from experimental animals of all genotypes at 24 h and 72 h after onset of ischemia. The dashed lines indicate the infarct area identified by diminished NeuN + HuC/D labeling. The infarct volume was calculated from serial brain slices for all animals of all genotypes and was found to be between 18 mm<sup>3</sup> (CCL2 KO, 24 h) and 35 mm<sup>3</sup> (QC KO, 24 h). (<b>C</b>) As a complementary measure of infarct size, increased immunosignals for Neurofilament L (NFL) in the ischemic area was quantified in serial sections. Here, the smallest ischemic areas were detected for CCL2 KO mice at 24 h and largest for QC KO at 72 h after ischemia. Note the complementary loss of NeuN + HuC/D and induction of NFL immunoreactivity in the ischemic area (I).</p>
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<p>Expression of QC and isoQC in ischemic brain areas. (<b>A</b>) Immunohistochemical labeling for QC and isoQC in the wild-type mouse brain at 24 h and 72 h after ischemia. (<b>B</b>) There were significant increases in the numbers of QC-immunoreactive neurons in infarct areas identified by NeuN + HuC/D labeling in consecutive brain sections for all genotypes (except QC KO) at both survival time points. (<b>C</b>) In contrast, there was significantly reduced isoQC immunoreactivity in infarct areas compared to the non-ischemic hemisphere. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; differences statistically significant versus control.</p>
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<p>Quantification of CCL2 expression and co-localization to neuronal and glial markers. (<b>A</b>) Left: single immunohistochemical labeling of CCL2 in the wild-type (WT) mouse brain 24 h and 72 h after ischemia. Note the absence of CCL2 immunoreactivity in a CCL2 KO mouse brain 72 h after ischemia. Right: note the post-ischemia time-dependent increase in signal intensity and spreading of the CCL2 immunosignal beyond the infarct (I) region demarked by the dashed line related to reduced NeuN + HuC/D labeling at 72 h. (<b>B</b>) Quantification of CCL2 immunosignals demonstrating increased CCL2 in the wild-type (WT) mouse brain at 24 and 72 h. Note that the mean values for CCL2 signals in QC KO and in isoQC KO are only half of the of the WT mice at both time points. (<b>C</b>) Appearance of CCL2 immunoreactivity in the ischemic cortex as extracellular spots, in association with vessels and in a glia-like shape. (<b>D</b>) Examples of double labeling of CCL2 with microglia markers Iba1, CD68 and TMEM119, with neurons (NeuN + HuC/D), astrocytes (GFAP) and oligodendrocytes (Olig2) in the ischemic cortex. Note the presence of CCL2 immunosignals in subsets of these neuronal and glial populations (arrows) except in oligodendrocytes. ** <span class="html-italic">p</span> &lt; 0.01; differences statistically significant versus control.</p>
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<p>Glia cell activation/recruitment in ischemic brain regions. (<b>A</b>) Triple immunofluorescent labeling of the microglial marker Iba1 and the astrocyte marker GFAP in combination with NeuN + HuC/D to identify the cortical infarct area (I). In the high magnification images (bottom), the activation of Iba1-positive microglia in the ischemic region and the presence of GFAP-immunoreactive reactive astrocytes in the border zone is evident. (<b>B</b>) Quantification of GFAP immunosignals in brain sections of mice of different genotypes. Note the instant increase in GFAP expression at 24 h for all genotypes, which is not increase further at 72 h. (<b>C</b>,<b>D</b>) In contrast, both numbers of activated microglia (<b>C</b>) and of MHC-II cells (<b>D</b>) only increase at 72 h after ischemia for all genotypes. Note that the mean values for both cell types in QC KO mice and in isoQC KO mice are only half of that in wild-type (WT) mice. Arrows in (<b>D</b>) point towards MHC-II-positive neurons (black). (<b>E</b>,<b>F</b>) The immunoreactivity for CD68 is increased after ischemia in all genotypes (<b>E</b>), whereas TMEM119 immunosignals are reduced (<b>F</b>). * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; differences statistically significant versus control. # <span class="html-italic">p</span> &lt; 0.05; ## <span class="html-italic">p</span> &lt; 0.01; differences statistically significant at 72 h versus 24 h.</p>
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<p>Quantification of chemokines in brain tissue and plasma of mice after ischemia. The concentrations of CCL2, CX3CL1, IL-1β, TNF-α and CCL17 were quantified by multiplex analyses in brain tissue of the ischemic hemisphere (<b>left</b>) and in plasma (<b>right</b>) at 24 h and 72 h after ischemia as indicated. Upregulation in the brain tissue is only selectively mirrored in the plasma, e.g., in case of CCL2. Please note the lack of CCL2 in CCL2 KO mice. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; differences statistically significant versus control. ## <span class="html-italic">p</span> &lt; 0.01; differences statistically significant at 72 h versus 24 h.</p>
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11 pages, 1103 KiB  
Protocol
Effectiveness of Physiotherapy for Improving Functionality, Participation, and Quality of Life after a Stroke: Study Protocol for a Randomized Controlled Clinical Trial
by Concepción Soto-Vidal, Victoria Calvo-Fuente, Ezequiel Hidalgo-Galante, Ester Cerezo-Téllez, Yolanda Pérez-Martín and Soraya Pacheco-da-Costa
J. Pers. Med. 2024, 14(8), 891; https://doi.org/10.3390/jpm14080891 - 22 Aug 2024
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Abstract
Background: Stroke survivors experience significant alterations in their daily functionality that has a negative impact on their functionality, participation, and quality of life. Person-centered approaches in Physical Therapy interventions that are focused on functional and meaningful goals help to minimize the impact of [...] Read more.
Background: Stroke survivors experience significant alterations in their daily functionality that has a negative impact on their functionality, participation, and quality of life. Person-centered approaches in Physical Therapy interventions that are focused on functional and meaningful goals help to minimize the impact of the alterations. Therefore, the aim of this study is to assess the effectiveness of a Physical Therapy intervention based on a goal-oriented approach with task-specific training for improving functionality, participation, and quality of life for people with Stroke. Methods: A single-blinded randomized controlled clinical trial will be developed. Adults over 50 years old diagnosed with Stroke over 6 months will be included in this study. Participants (n = 62) will be randomly allocated into two groups: The experimental group (n = 31) will receive 30 sessions, three per week during 10 weeks, of Physical Therapy sessions of goal-directed and task-specific training. The control group (n = 31) will follow the same intervention intensity of their usual Physical Therapy treatment. The primary outcome variables quality of life (NewsQol), participation (Ox-PAQ), and gait functionality (FAC) and the secondary outcome variables functional disability (BI), postural control (PASS), dynamic trunk balance (TIS), and functional goals (GAS) will be measured at baseline, after group interventions (10 weeks), and 6 months after the baseline. Statistical analyses will include repeated-measures ANOVA, Student’s t-test, or the Mann–Whitney U-test, with a 95% confidence interval and significance level of p < 0.05. Conclusion: Person-centered approaches in Physical Therapy interventions may yield better outcomes in functionality, participation, and quality of life for Stroke patients compared to standardized interventions. Trial registration: ClinicalTrials.gov: NCT06165666 (December 2023). Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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<p>Consort diagram: flow of participants throughout this study.</p>
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