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Parkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of α-synuclein (α-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified α-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that α-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of α-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies.
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Doença de Gaucher/metabolismo , Glucosilceramidase/metabolismo , alfa-Sinucleína/metabolismo , Animais , Encéfalo/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Retroalimentação Fisiológica , Doença de Gaucher/patologia , Glucosilceramidas/metabolismo , Humanos , Lisossomos/metabolismo , Camundongos , Neurônios/metabolismoRESUMO
Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated) have been measured. A pulsed, rotationally cold molecular beam (Ei = 35 kJ mol-1) of OH was scattered from refreshed liquid surfaces in a vacuum. Spatially and temporally resolved OH number densities were measured by pulsed, planar laser-induced fluorescence. Results are compared with those for the inert liquid perfluoropolyether. The clearly asymmetric distributions for 45° incidence add to the weight of evidence for predominantly impulsive scattering from all three liquids. However, we propose that significant differences in their shapes may be diagnostic of contrasting reaction mechanisms. Direct, near-specular trajectories survive preferentially on squalene, consistent with an addition mechanism removing those at more backward angles. This trend is reversed for squalane, as expected for direct abstraction. The results reinforce the need to consider the effects of composition-dependent contributions from different reaction mechanisms in the modeling of OH-aging of atmospheric aerosol particles.
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CONTEXT: Latency is a reliable temporal metric used to evaluate sensorimotor integration of the fibularis longus (FL) and fibularis brevis (FB) during lateral ankle sprain perturbations. Currently, no clinical recommendations exist to select appropriate thresholds to evaluate the closed-loop reflex response of the lateral ankle musculature. The purpose of this study was to assess threshold value on latency of the FL and FB during an unanticipated inversion perturbation that simulates the mechanism of a lateral ankle sprain. DESIGN: Descriptive laboratory study. METHODS: Twenty healthy adults with no history of lateral ankle sprain injury completed an unanticipated single-leg drop landing onto a 25° laterally inclined force platform from a height of 30 cm. Surface electromyography recorded muscle activity data from the FL and FB during the inversion perturbation. Latency was identified at points where muscle activity exceeded 2, 5, and 10 SD above the average muscle activity 200 milliseconds prior to foot contact, and compared across threshold value using a 1-way analysis of variance (P < .05). RESULTS: The 2 SD threshold was significantly shorter than both 5 SD and 10 SD thresholds for the FL (P < .01) and FB (P < .01). Likewise, the 5 SD threshold was significantly shorter than the 10 SD thresholds for FL (P = .004) and FB (P = .003). CONCLUSIONS: More sensitive thresholds results in a shorter closed-loop reflexive response compared to the more rigorous thresholds. We recommend that selection of the appropriate threshold to identify latency of the lateral ankle musculature should be based on the device used to simulate a lateral ankle sprain and the ankle inversion velocity produced during the ankle inversion perturbation.
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Traumatismos do Tornozelo , Tornozelo , Adulto , Humanos , Extremidade Inferior , Articulação do Tornozelo , ReflexoRESUMO
Inelastic collisions of OH with an inert liquid perfluoropolyether (PFPE) surface have been studied experimentally. A pulsed molecular beam of OH with a kinetic energy distribution peaking at 35 kJ mol-1 was directed at a continually refreshed PFPE surface. OH molecules were detected state-selectively with spatial and temporal resolution by pulsed, planar laser-induced fluorescence. The scattered speed distributions were confirmed to be strongly superthermal, regardless of the incidence angle (0° or 45°). Angular scattering distributions were measured for the first time; their reliability was confirmed through extensive Monte Carlo simulations of experimental averaging effects, described in Paper II [A. G. Knight et al., J. Chem. Phys. 158, 244705 (2023)]. The distributions depend markedly on the incidence angle and are correlated with scattered OH speed, consistent with predominantly impulsive scattering. For 45° incidence, the angular distributions are distinctly asymmetric to the specular side but peak at sub-specular angles. This, along with the breadth of the distributions, is incompatible with scattering from a surface that is flat on a molecular scale. New molecular dynamics simulations corroborate the roughness of the PFPE surface. A subtle but unexpected systematic dependence of the angular distribution on the OH rotational state was found, which may be dynamical in origin. The OH angular distributions are similar to those for kinematically similar Ne scattering from PFPE and hence not strongly perturbed by OH being a linear rotor. The results here are broadly compatible with prior predictions from independent quasiclassical trajectory simulations of OH scattering from a model-fluorinated self-assembled monolayer surface.
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We have analyzed the effects of the spreads in experimental parameters on the reliability of speeds and angular distributions extracted from a generic surface-scattering experiment based on planar laser-induced fluorescence detection. The numerical model assumes a pulsed beam of projectile molecules is directed at a surface. The spatial distribution of the scattered products is detected by imaging the laser-induced fluorescence excited by a thin, pulsed sheet of laser light. Monte Carlo sampling is used to select from realistic distributions of the experimental parameters. The key parameter is found to be the molecular-beam diameter, expressed as a ratio to the measurement distance from the point of impact. Measured angular distributions are negligibly distorted when this ratio is <â¼10%. Measured most-probable speeds are more tolerant, being undistorted when it is <â¼20%. In contrast, the spread of speeds or of corresponding arrival times in the incident molecular beam has only very minor systematic effects. The thickness of the laser sheet is also unimportant within realistic practical limits. These conclusions are broadly applicable to experiments of this general type. In addition, we have analyzed the specific set of parameters designed to match the experiments on OH scattering from a liquid perfluoropolyether (PFPE) surface in the Paper I [Roman et al., J. Chem. Phys. 158, 244704 (2023)]. This reveals that the detailed form of the molecular-beam profile is important, particularly on apparent angular distributions, for geometric reasons that we explain. Empirical factors have been derived to correct for these effects.
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ABSTRACT: Krings, BM, Shepherd, BD, Swain, JC, Turner, AJ, Chander, H, Waldman, HS, McAllister, MJ, Knight, AC, and Smith, JW. Impact of fat grip attachments on muscular strength and neuromuscular activation during resistance exercise. J Strength Cond Res 35(2S): S152-S157, 2021-The purpose of this study was to examine the acute effects of Fat Gripz (FG) on muscular activation and strength. Resistance trained men (n = 15; age = 22.4 ± 2.3 years; mass = 83.2 ± 11.1 kg) performed 2 experimental trials in a randomized order. Subjects completed 1 repetition maximum (1RM) testing with an Olympic barbell (OB) and with FG attached to an OB during the exercises of deadlift, bent-over row, upright row, concentration curl, and completed maximum repetitions of pull-ups until failure. Surface electromyography (EMG) was used to measure muscle activity from 8 upper extremity muscles (trapezius, medial deltoid, biceps brachii, triceps brachii, flexor carpi radialis, flexor carpi ulnaris, extensor carpi radialis, and extensor carpi ulnaris), while performing maximal voluntary isometric contractions during 1RM trials and while performing maximum number of pull-ups. When using the FG, 1RM strength was significantly decreased for each exercise, and the maximal number of pull-ups completed was significantly lower. Electromyography muscle activity was significantly increased in the forearm and shoulder muscles, but significantly decreased in the upper arm muscles with the use of FG during deadlift, bent-over row, and pull-ups. However, there were no differences for EMG activity for upright row and concentration curl. Differences in maximal strength, pull-up performance, and EMG activity with FG use may be due to the different muscle length positions. Although FG training may increase neuromuscular activation, decrements in muscular strength may result in prescribing low training loads that may not be ideal for building muscular strength.
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Treinamento Resistido , Adulto , Eletromiografia , Força da Mão , Humanos , Contração Isométrica , Masculino , Força Muscular , Músculo Esquelético , Adulto JovemRESUMO
The purpose of this study was to evaluate the use of compressible soft robotic sensors (C-SRS) in determining plantar pressure to infer vertical and shear forces in wearable technology: A ground reaction pressure sock (GRPS). To assess pressure relationships between C-SRS, pressure cells on a BodiTrakTM Vector Plate, and KistlerTM Force Plates, thirteen volunteers performed three repetitions of three different movements: squats, shifting center-of-pressure right to left foot, and shifting toes to heels with C-SRS in both anterior-posterior (A/P) and medial-lateral (M/L) sensor orientations. Pearson correlation coefficient of C-SRS to BodiTrakTM Vector Plate resulted in an average R-value greater than 0.70 in 618/780 (79%) of sensor to cell comparisons. An average R-value greater than 0.90 was seen in C-SRS comparison to KistlerTM Force Plates during shifting right to left. An autoregressive integrated moving average (ARIMA) was conducted to identify and estimate future C-SRS data. No significant differences were seen in sensor orientation. Sensors in the A/P orientation reported a mean R2 value of 0.952 and 0.945 in the M/L sensor orientation, reducing the effectiveness to infer shear forces. Given the high R values, the use of C-SRSs to infer normal pressures appears to make the development of the GRPS feasible.
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The linearity of soft robotic sensors (SRS) was recently validated for movement angle assessment using a rigid body structure that accurately depicted critical movements of the foot-ankle complex. The purpose of this study was to continue the validation of SRS for joint angle movement capture on 10 participants (five male and five female) performing ankle movements in a non-weight bearing, high-seated, sitting position. The four basic ankle movements-plantar flexion (PF), dorsiflexion (DF), inversion (INV), and eversion (EVR)-were assessed individually in order to select good placement and orientation configurations (POCs) for four SRS positioned to capture each movement type. PF, INV, and EVR each had three POCs identified based on bony landmarks of the foot and ankle while the DF location was only tested for one POC. Each participant wore a specialized compression sock where the SRS could be consistently tested from all POCs for each participant. The movement data collected from each sensor was then compared against 3D motion capture data. R-squared and root-mean-squared error averages were used to assess relative and absolute measures of fit to motion capture output. Participant robustness, opposing movements, and gender were also used to identify good SRS POC placement for foot-ankle movement capture.
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Articulação do Tornozelo/fisiologia , Articulações do Pé/fisiologia , Dispositivos Eletrônicos Vestíveis , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Movimento/fisiologia , Adulto JovemRESUMO
Postural stability has been shown to be impacted by footwear and task performed. This study analysed the impact of two military footwear, standard boot (STB) and minimalist boot (MTB) on postural stability, before (PRE) and after (POST) a load carriage task. Sixteen participants were tested for postural stability using sensory organisation and motor control tests on Neurocom Equitest™. Postural sway, equilibrium scores and postural latencies were analysed using a two-factor repeated measures ANOVA: boot type (STB-MTB) × time (PRE-POST) load carriage task. Significantly greater postural sway variables, lower balance scores and slower postural latencies were seen in STB and POST load carriage conditions (p < .05). The results suggest that MTB exhibited greater balance compared to STB in balance conditions that rely on somatosensory feedback and that balance is lowered after a load carriage task. Decrements in postural stability could be attributed to boot design characteristics and muscular exertion due to the load carriage task. Practitioner Summary: Maintaining optimal postural stability is crucial in military. Impact of military footwear types and load carriage task on postural stability are addressed. Findings provide footwear design and physical exertion implications on postural stability leading to potential interventions that reduce postural stability decrements; thereby, reducing potential falls and fall related injuries.
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Militares , Equilíbrio Postural/fisiologia , Sapatos/efeitos adversos , Suporte de Carga/fisiologia , Carga de Trabalho , Acidentes por Quedas/prevenção & controle , Adulto , Ergonomia , Feminino , Humanos , Masculino , Traumatismos Ocupacionais/etiologia , Traumatismos Ocupacionais/prevenção & controle , Adulto JovemRESUMO
CONTEXT: Lateral ankle sprains are a common injury in which the mechanics of injury have been extensively studied. However, the anticipatory mechanisms to ankle inversion perturbations are not well understood. OBJECTIVE: To examine lower-extremity kinematics, including spatial and temporal variables of maximum inversion displacement and maximum inversion velocity, during landings on a tilted surface using a new experimental protocol to replicate a lateral ankle sprain. SETTING: Three-dimensional motion analysis laboratory. PARTICIPANTS: A total of 23 healthy adults. INTERVENTIONS: Participants completed unexpected (UE) and expected (EXP) unilateral landings onto a tilted surface rotated 25° in the frontal plane from a height of 30 cm. MAIN OUTCOME MEASURES: Ankle, knee, and hip kinematics at each discrete time point from 150 ms pre-initial contact (IC) to 150 ms post-IC, in addition to maximum ankle inversion and maximum inversion velocity, were compared between UE and EXP landings. RESULTS: The UE landing produced significantly greater maximum inversion displacement (P < .01) and maximum inversion velocity (P = .02) than the EXP landing. Significantly less ankle inversion and internal rotation were found during pre-IC, whereas during post-IC, significantly greater ankle inversion, ankle internal rotation, knee flexion, and knee abduction were observed for the UE landing (P < .05). In addition, significantly less hip flexion and hip adduction were observed for the UE landing during pre-IC and post-IC (P < .05). CONCLUSIONS: Differences in the UE and EXP landings indicate the experimental protocol presented a UE inversion perturbation that approximates the mechanism of a lateral ankle sprain. Furthermore, knowledge of the inversion perturbation elicited a hip-dominant strategy, which may be utilized to assist with ankle joint stabilization during landing to further protect the lateral ankle from injury.
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Traumatismos do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Amplitude de Movimento Articular , Entorses e Distensões/fisiopatologia , Tornozelo , Feminino , Quadril , Humanos , Joelho , Extremidade Inferior , Masculino , Movimento , Rotação , Adulto JovemRESUMO
Lysosomes are responsible for degradation and recycling of bulky cell material, including accumulated misfolded proteins and dysfunctional organelles. Increasing evidence implicates lysosomal dysfunction in several neurodegenerative disorders, including Parkinson's disease and related synucleinopathies, which are characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies. Studies of lysosomal proteins linked to neurodegenerative disorders present an opportunity to uncover specific molecular mechanisms and pathways that contribute to neurodegeneration. Loss-of-function mutations in a lysosomal protein, ATP13A2 (PARK9), cause Kufor-Rakeb syndrome that is characterized by early-onset parkinsonism, pyramidal degeneration and dementia. While loss of ATP13A2 function plays a role in α-syn misfolding and toxicity, the normal function of ATP13A2 in the brain remains largely unknown. Here, we performed a screen to identify ATP13A2 interacting partners, as a first step toward elucidating its function. Utilizing a split-ubiquitin membrane yeast two-hybrid system that was developed to identify interacting partners of full-length integral membrane proteins, we identified 43 novel interactors that primarily implicate ATP13A2 in cellular processes such as endoplasmic reticulum (ER) translocation, ER-to-Golgi trafficking and vesicular transport and fusion. We showed that a subset of these interactors modified α-syn aggregation and α-syn-mediated degeneration of dopaminergic neurons in Caenorhabditis elegans, further suggesting that ATP13A2 and α-syn are functionally linked in neurodegeneration. These results implicate ATP13A2 in vesicular trafficking and provide a platform for further studies of ATP13A2 in neurodegeneration.
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Dobramento de Proteína/efeitos dos fármacos , ATPases Translocadoras de Prótons/metabolismo , alfa-Sinucleína/metabolismo , alfa-Sinucleína/toxicidade , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Ligação Proteica/efeitos dos fármacos , Reprodutibilidade dos Testes , Técnicas do Sistema de Duplo-Híbrido , alfa-Sinucleína/químicaRESUMO
The purpose of the study was to examine static postural control/balance in young adults with intellectual and developmental disabilities (IDD) and typically developing (TD) young adults before, during, and after an inclusive badminton intervention. Eight participants (four IDD-BADM and four TD-BADM) participated in a 12-week inclusive badminton intervention, with the other eight participants as matched controls (four IDD-CONTR and four TD-CONTR) (74.19 kg ± 9.8 kg, 171.96 cm ± 5.4 cm; 21.7 ± 1.8 years of age; nine females and seven males; eight with IDD and eight TD). The study followed a repeated measures design (pre, mid, post) before the intervention, at 6 weeks, and after 12 weeks. Static postural sway conditions included: bilateral stance eyes open (20 s), eyes closed (10 s), foam eyes open (20 s), foam eyes closed (10 s), and unilateral stance eyes open (10 s) and foam eyes open (10 s). Sway measurements included: average anterior/posterior (A/P) displacement (in), average medial/lateral (M/L) displacement (in), average 95% ellipsoid area (in2), and average velocity (ft/s). Significant time × group interactions were reported for average velocity (EO) (p = 0.030), average length (EO) (p = 0.030), 95% ellipsoid area (EO) (p = 0.049), and average A/P displacement (1LEO) (p = 0.036) for IDD-BADM. Significant time main effects were reported for average A/P displacement (FEO) (p = 0.040) for IDD groups. Significant time main effects were reported for average M/L displacement (EO) (p = 0.001), (EC) (p = 0.004), (FEO) (p = 0.005), (FEC) (p = 0.004), and average A/P displacement (EO) (p = 0.006) and (FEO) (p = 0.005) for TD groups. An inclusive badminton program indicated evidence of improved static postural control for those with IDD. However, no significant differences were reported for TD peers.
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Deficiências do Desenvolvimento , Equilíbrio Postural , Masculino , Criança , Feminino , Adulto Jovem , Humanos , Projetos de PesquisaRESUMO
CONTEXT: The dominant and nondominant legs respond asymmetrically during landing tasks, and this difference may occur during an inversion perturbation and provide insight into the role of ankle-evertor and -invertor muscle activity. OBJECTIVE: To determine if there is a difference in the ratio of evertor to invertor activity between the dominant and nondominant legs and outer-sole conditions when the ankle is forced into inversion. DESIGN: Repeated-measures single-group design. SETTING: University laboratory. PARTICIPANTS: 15 physically active healthy volunteers with no previous history of an ankle sprain or lower extremity surgery or fracture. INTERVENTIONS: An outer sole with fulcrum was used to cause 25° of inversion at the subtalar joint after landing from a 27-cm step-down task. Participants performed 10 fulcrum trials on both the dominant and nondominant leg. MAIN OUTCOME MEASURES: The ratio of evertor to invertor muscle activity 200 ms before and 200 ms after the inversion perturbation was measured using electromyography. This ratio was the dependent variable. Independent variables included outer-sole condition (fulcrum, flat), leg (dominant, nondominant), and time (prelanding, postlanding). The data were analyzed with separate 2-way repeated-measures ANOVA, 1 for the prelanding ratios and 1 for the postlanding ratios. RESULTS: For the postlanding ratios, the fulcrum outer sole had a significantly greater (P < .05) ratio than the flat outer sole, and the nondominant leg had a significantly greater (P < .05) ratio than the dominant leg. CONCLUSIONS: These results indicate that a greater evertor response is produced when the ankle is forced into inversion, and a greater response is produced for the nondominant leg, which may function better during a postural-stabilizing task than the dominant leg.
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Traumatismos do Tornozelo/fisiopatologia , Lateralidade Funcional/fisiologia , Contração Muscular , Músculo Esquelético/fisiopatologia , Entorses e Distensões/fisiopatologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The Star Excursion Balance Test (SEBT) is a common assessment used across clinical and research settings to test dynamic standing balance. The primary measure of this test is maximal reaching distance performed by the non-stance limb. Response time (RT) is a critical cognitive component of dynamic balance control and the faster the RT, the better the postural control and recovery from a postural perturbation. However, the measure of RT has not been done in conjunction with SEBT, especially with musculoskeletal fatigue. The purpose of this study is to examine RT during a SEBT, creating a modified SEBT (mSEBT), with a secondary goal to examine the effects of muscular fatigue on RT during SEBT. Sixteen healthy young male and female adults [age: 20 ± 1 years; height: 169.48 ± 8.2 cm; weight: 67.93 ± 12.7 kg] performed the mSEBT in five directions for three trials, after which the same was repeated with a response time task using Blazepod™ with a random stimulus. Participants then performed a low-intensity musculoskeletal fatigue task and completed the above measures again. A 2 × 2 × 3 repeated measures ANOVA was performed to test for differences in mean response time across trials, fatigue states, and leg reach as within-subjects factors. All statistical analyses were conducted in JASP at an alpha level of 0.05. RT was significantly faster over the course of testing regardless of reach leg or fatigue state (p = 0.023). Trial 3 demonstrated significantly lower RT compared to Trial 1 (p = 0.021). No significant differences were found between fatigue states or leg reach. These results indicate that response times during the mSEBT with RT is a learned skill that can improve over time. Future research should include an extended familiarization period to remove learning effects and a greater fatigue state to test for differences in RT during the mSEBT.
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Pé , Equilíbrio Postural , Adulto , Humanos , Masculino , Feminino , Adulto Jovem , Tempo de Reação , Equilíbrio Postural/fisiologia , Fadiga , CogniçãoRESUMO
Background: Occupational workers at altitudes are more prone to falls, leading to catastrophic outcomes. Acrophobia, height-related anxiety, and affected executive functions lead to postural instabilities, causing falls. This study investigated the effects of repeated virtual height exposure and training on cognitive processing and height-related anxiety. Methods: Twenty-eight healthy volunteers (age 20.48 ± 1.26 years; mass 69.52 ± 13.78 kg) were recruited and tested in seven virtual environments (VE) [ground (G), 2-story altitude (A1), 2-story edge (E1), 4-story altitude (A2), 4-story edge (E2), 6-story altitude (A3), and 6-story edge (E3)] over three days. At each VE, participants identified occupational hazards present in the VE and completed an Attitude Towards Heights Questionnaire (ATHQ) and a modified State-Trait Anxiety Inventory Questionnaire (mSTAIQ). The number of hazards identified and the ATHQ and mSTAIQ scores were analyzed using a 7 (VE; G, A1, A2, A3, E1, E2, E3) x 3 (DAY; DAY 1, DAY 2, DAY 3) factorial repeated measures analysis of variance. Results: The participants identified the lowest number of hazards at A3 and E3 VEs and on DAY 1 compared to other VEs and DAYs. ATHQ scores were lowest at G, A1, and E1 VEs. Conclusion: Cognitive processing is negatively affected by virtual altitudes, while it improves with short-term training. The features of virtual reality, such as higher involvement, engagement, and reliability, make it a better training tool to be considered in ergonomic settings. The findings of this study will provide insights into cognitive dual-tasking at altitude and its challenges, which will aid in minimizing occupational falls.
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The development of wearable technology, which enables motion tracking analysis for human movement outside the laboratory, can improve awareness of personal health and performance. This study used a wearable smart sock prototype to track foot-ankle kinematics during gait movement. Multivariable linear regression and two deep learning models, including long short-term memory (LSTM) and convolutional neural networks, were trained to estimate the joint angles in sagittal and frontal planes measured by an optical motion capture system. Participant-specific models were established for ten healthy subjects walking on a treadmill. The prototype was tested at various walking speeds to assess its ability to track movements for multiple speeds and generalize models for estimating joint angles in sagittal and frontal planes. LSTM outperformed other models with lower mean absolute error (MAE), lower root mean squared error, and higher R-squared values. The average MAE score was less than 1.138° and 0.939° in sagittal and frontal planes, respectively, when training models for each speed and 2.15° and 1.14° when trained and evaluated for all speeds. These results indicate wearable smart socks to generalize foot-ankle kinematics over various walking speeds with relatively low error and could consequently be used to measure gait parameters without the need for a lab-constricted motion capture system.
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Protein misfolding and aggregation are key pathological features observed in numerous neurodegenerative diseases, including the misfolding of α-synuclein (α-syn) in Parkinson's disease (PD) and ß-amyloid in Alzheimer's disease. While this phenomenon is widely observed, the etiology and progression of these diseases is not fully understood. Furthermore, there is a lack of therapeutic treatments directed at halting the progression and neurodegeneration associated with these diseases. This demands a need for an inexpensive, easy to manipulate multicellular organism to conduct both genetic and chemical screens within to identify factors that may play a pivotal role in the pathology of these diseases. Herein, we describe methodology involved in identifying genetic modifiers of α-syn misfolding and toxicity in the nematode roundworm, Caenorhabditis elegans. Transgenic nematodes engineered to express human α-syn in the body wall muscles or dopaminergic (DA) neurons result in formation of cytoplasmic puncta or DA neurodegeneration, respectively. Using these models, we describe the use of RNA interference (RNAi) and transgenic gene expression to functionally elucidate potential therapeutic gene targets that alter α-syn misfolding and DA neurotoxicity.
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Caenorhabditis elegans/fisiologia , Dopamina/metabolismo , Neurônios/metabolismo , Doença de Parkinson/patologia , Proteínas Recombinantes/metabolismo , alfa-Sinucleína/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Morte Celular , Clonagem Molecular , Modelos Animais de Doenças , Humanos , Músculos/metabolismo , Neurônios/citologia , Especificidade de Órgãos , Dobramento de Proteína , Interferência de RNARESUMO
When the ankle is forced into inversion, the speed at which this movement occurs may affect the extent of injury. The purpose of this investigation was to develop a fulcrum device to mimic the mechanism of a lateral ankle sprain and to determine the reliability and validity of the temporal variables produced by this device. Additionally, this device was used to determine if a single previous lateral ankle sprain or ankle taping effected the time to maximum inversion and/or mean inversion speed. Twenty-six participants (13 with history of a single lateral ankle sprain and 13 with no history of injury) completed the testing. The participants completed testing on three separate days, performing 10 trials with the fulcrum per leg on each testing day, and tape was applied to both ankles on one testing day. No significant interactions or main effects were found for either previous injury or ankle taping, but good reliability was found for time to maximum inversion (ICC = .81) and mean inversion speed (ICC = .79). The findings suggest that although neither variable was influenced by the history of a single previous lateral ankle sprain or ankle taping, both variables demonstrated good reliability and construct validity, but not discriminative validity.
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Traumatismos do Tornozelo/fisiopatologia , Articulação do Tornozelo/fisiopatologia , Fita Atlética , Entorses e Distensões/fisiopatologia , Traumatismos do Tornozelo/prevenção & controle , Fenômenos Biomecânicos , Desenho de Equipamento , Feminino , Humanos , Masculino , Movimento/fisiologia , Reprodutibilidade dos Testes , Entorses e Distensões/prevenção & controle , Fatores de Tempo , Adulto JovemRESUMO
The latency of the peroneus longus may be a key factor in the prevention of lateral ankle sprains (LASs). In addition, ankle taping is often applied to help prevent LASs. The purpose of this study was to determine the effects of a previous LAS and ankle taping on the latency of the peroneus longus after an inversion perturbation. Twenty-six participants, including 13 participants with no previous history of a LAS and 13 participants with a history of a single LAS completed the testing. Ankle taping was applied in a closed basket weave technique on one of the two testing days. The latency of the peroneus longus was determined by the onset of muscle activity exceeding 10 SD from baseline activity, after initiation of the 25 degrees inversion perturbation. A significant main effect (p < 0.05) was present for the ankle support condition, with ankle taping causing a significant reduction in latency of the peroneus longus (65.04 +/- 10.81 to 57.70 +/- 9.39 ms). There was no difference (p > 0.05) in latency between the injury groups. Ankle taping, immediately after application, reduces the latency of the peroneus longus among participants with and without a history of a LAS.
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Traumatismos do Tornozelo/prevenção & controle , Fita Atlética , Músculo Esquelético/fisiologia , Entorses e Distensões/prevenção & controle , Articulação do Tornozelo/fisiologia , Articulação do Tornozelo/fisiopatologia , Feminino , Humanos , Masculino , Tempo de Reação , Fatores de Tempo , Adulto JovemRESUMO
This study examined lower extremity joint kinematics in individuals with chronic ankle instability (CAI) and controls during unanticipated and anticipated single-leg drop landings onto a laterally inclined platform. Physically active adults with CAI 15 (n = 15) and controls (n = 15) performed an unanticipated and anticipated 30 cm single-leg drop landing onto a 20° laterally inclined platform. Three-dimensional ankle, knee and hip-joint kinematics were recorded 200 ms pre- to 200 post-landing and analysed with a 2 (group) × 2 (landing condition) SPM ANOVA (p < 0.05). Results revealed individuals with CAI displayed significantly greater ankle internal rotation post-landing across both landing conditions. Anticipated landings elicited significantly greater pre-landing ankle inversion and external rotation, knee abduction and hip adduction. Additionally, significantly less ankle inversion, knee and hip flexion, and knee adduction and hip abduction were present during post-landing of the anticipated landing. Greater ankle internal rotation during landing may contribute to the ankle 'giving way' in individuals with CAI. However, preparatory and reactive proximal-joint kinematics were similar in both groups during landing. This highlights the possible role of the knee and hip joints in assisting with ankle-joint stability during anticipated inversion perturbations.