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1.
PLoS Biol ; 22(1): e3002169, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38271304

RESUMEN

Individual signaling pathways, such as fibroblast growth factors (FGFs), can regulate a plethora of inductive events. According to current paradigms, signal-dependent transcription factors (TFs), such as FGF/MapK-activated Ets family factors, partner with lineage-determining factors to achieve regulatory specificity. However, many aspects of this model have not been rigorously investigated. One key question relates to whether lineage-determining factors dictate lineage-specific responses to inductive signals or facilitate these responses in collaboration with other inputs. We utilize the chordate model Ciona robusta to investigate mechanisms generating lineage-specific induction. Previous studies in C. robusta have shown that cardiopharyngeal progenitor cells are specified through the combined activity of FGF-activated Ets1/2.b and an inferred ATTA-binding transcriptional cofactor. Here, we show that the homeobox TF Lhx3/4 serves as the lineage-determining TF that dictates cardiopharyngeal-specific transcription in response to pleiotropic FGF signaling. Targeted knockdown of Lhx3/4 leads to loss of cardiopharyngeal gene expression. Strikingly, ectopic expression of Lhx3/4 in a neuroectodermal lineage subject to FGF-dependent specification leads to ectopic cardiopharyngeal gene expression in this lineage. Furthermore, ectopic Lhx3/4 expression disrupts neural plate morphogenesis, generating aberrant cell behaviors associated with execution of incompatible morphogenetic programs. Based on these findings, we propose that combinatorial regulation by signal-dependent and lineage-determinant factors represents a generalizable, previously uncategorized regulatory subcircuit we term "cofactor-dependent induction." Integration of this subcircuit into theoretical models will facilitate accurate predictions regarding the impact of gene regulatory network rewiring on evolutionary diversification and disease ontogeny.


Asunto(s)
Ciona intestinalis , Regulación del Desarrollo de la Expresión Génica , Animales , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/fisiología , Ciona intestinalis/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
2.
J Clin Med ; 12(19)2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37835021

RESUMEN

The forces applied during a spinal manipulation produce a neuromuscular response in the paraspinal muscles. A systematic evaluation of the factors involved in producing this muscle activity provides a clinical insight. The purpose of this study is to quantify the effect of treatment factors (manipulation sequence and manipulation site) and response factors (muscle layer, muscle location, and muscle side) on the neuromuscular response to spinal manipulation. The surface and indwelling electromyographies of 8 muscle sites were recorded during lumbar side-lying manipulations in 20 asymptomatic participants. The effects of the factors on the number of muscle responses and the muscle activity onset delays were compared using mixed-model linear regressions, effect sizes, and equivalence testing. The treatment factors did not reveal statistical differences between the manipulation sequences (first or second) or manipulation sites (L3 or SI) in the number of muscle responses (p = 0.11, p = 0.28, respectively), or in muscle activity onset delays (p = 0.35 p = 0.35, respectively). There were significantly shorter muscle activity onset delays in the multifidi compared to the superficial muscles (p = 0.02). A small effect size of side (d = 0.44) was observed with significantly greater number of responses (p = 0.02) and shorter muscle activity onset delays (p < 0.001) in the muscles on the left side compared to the right. The location, layer, and side of the neuromuscular responses revealed trends of decreasing muscle response rates and increasing muscle activity onset delays as the distance from the manipulation site increased. These results build on the body of work suggesting that the specificity of manipulation site may not play a role in the neuromuscular response to spinal manipulation-at least within the lumbar spine. In addition, these results demonstrate that multiple manipulations performed in similar areas (L3 and S1) do not change the response significantly, as well as contribute to the clinical understanding that the muscle response rate is higher and with a shorter delay, the closer it is to the manipulation.

3.
Sensors (Basel) ; 20(19)2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-32998329

RESUMEN

Quantitative assessments of patient movement quality in osteoarthritis (OA), specifically spatiotemporal gait parameters (STGPs), can provide in-depth insight into gait patterns, activity types, and changes in mobility after total knee arthroplasty (TKA). A study was conducted to benchmark the ability of multiple deep neural network (DNN) architectures to predict 12 STGPs from inertial measurement unit (IMU) data and to identify an optimal sensor combination, which has yet to be studied for OA and TKA subjects. DNNs were trained using movement data from 29 subjects, walking at slow, normal, and fast paces and evaluated with cross-fold validation over the subjects. Optimal sensor locations were determined by comparing prediction accuracy with 15 IMU configurations (pelvis, thigh, shank, and feet). Percent error across the 12 STGPs ranged from 2.1% (stride time) to 73.7% (toe-out angle) and overall was more accurate in temporal parameters than spatial parameters. The most and least accurate sensor combinations were feet-thighs and singular pelvis, respectively. DNNs showed promising results in predicting STGPs for OA and TKA subjects based on signals from IMU sensors and overcomes the dependency on sensor locations that can hinder the design of patient monitoring systems for clinical application.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Aprendizaje Profundo , Marcha , Osteoartritis , Humanos , Osteoartritis/fisiopatología , Caminata
4.
J Appl Biomech ; 36(6): 423-435, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32971516

RESUMEN

People developing transient low back pain during standing have altered control of their spine and hips during standing tasks, but the transfer of these responses to other tasks has not been assessed. This study used video fluoroscopy to assess lumbar spine intervertebral kinematics of people who do and do not develop standing-induced low back pain during a seated chair-tilting task. A total of 9 females and 8 males were categorized as pain developers (5 females and 3 males) or nonpain developers (4 females and 5 males) using a 2-hour standing exposure; pain developers reported transient low back pain and nonpain developers did not. Participants were imaged with sagittal plane fluoroscopy at 25 Hz while cyclically tilting their pelvises anteriorly and posteriorly on an unstable chair. Intervertebral angles, relative contributions, and anterior-posterior translations were measured for the L3/L4, L4/L5, and L5/S1 joints and compared between sexes, pain groups, joints, and tilting directions. Female pain developers experienced more extension in their L5/S1 joints in both tilting directions compared with female nonpain developers, a finding not present in males. The specificity in intervertebral kinematics to sex-pain group combinations suggests that these subgroups of pain developers and nonpain developers may implement different control strategies.

5.
Front Neurosci ; 14: 761, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32848549

RESUMEN

Concussion or mild traumatic brain injury (mTBI) in athletes can cause persistent symptoms, known as post-concussion syndrome (PCS), and repeated injuries may increase the long-term risk for an athlete to develop neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), and Alzheimer's disease (AD). The Center for Disease Control estimates that up to 3.8 million sport-related mTBI are reported each year in the United States. Despite the magnitude of the phenomenon, there is a current lack of comprehensive prognostic indicators and research has shown that available monitoring tools are moderately sensitive to short-term concussion effects but less sensitive to long-term consequences. The overall aim of this review is to discuss novel, quantitative, and objective measurements that can predict long-term outcomes following repeated sports-related mTBIs. The specific objectives were (1) to provide an overview of the current clinical and biomechanical tools available to health practitioners to ensure recovery after mTBIs, (2) to synthesize potential biological mechanisms in animal models underlying the long-term adverse consequences of mTBIs, (3) to discuss the possible link between repeated mTBI and neurodegenerative diseases, and (4) to discuss the current knowledge about fluid biomarkers for mTBIs with a focus on novel exosomal biomarkers. The conclusions from this review are that current post-concussion clinical tests are not sufficiently sensitive to injury and do not accurately quantify post-concussion alterations associated with repeated mTBIs. In the current review, it is proposed that current practices should be amended to include a repeated symptom inventory, a cognitive assessment of executive function and impulse control, an instrumented assessment of balance, vestibulo-ocular assessments, and an improved panel of blood or exosome biomarkers.

6.
Artículo en Inglés | MEDLINE | ID: mdl-32853329

RESUMEN

OBJECTIVE: In this study we examined the temporal stability of the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) within NCAA Division I athletes across various timepoints using an exhaustive series of statistical models. METHODS: Within a cohort design, 48 athletes completed repeated baseline ImPACT assessments at various timepoints. Intraclass correlation coefficients (ICC) were calculated using a two-way mixed effects model with absolute agreement. RESULTS: Four ImPACT composite scores (Verbal Memory, Visual Memory, Visual Motor Speed, and Reaction Time) demonstrated moderate reliability (ICC = 0.51-0.66) across the span of a typical Division I athlete's career, which is below previous reliability recommendations (0.90) for measures used in individual decision-making. No evidence of fixed bias was detected within Verbal Memory, Visual Motor Speed, or Reaction Time composite scores, and minimal detectable change values exceeded the limits of agreement. CONCLUSIONS: The demonstrated temporal stability of the ImPACT falls below the published recommendations, and as such, fails to provide robust support for the NCAA's recommendation to obtain a single preparticipation cognitive baseline for use in sports-related concussion management throughout an athlete's career. Clinical interpretation guidelines are provided for clinicians who utilize baseline ImPACT scores for later performance comparisons.

7.
J Sports Sci ; 38(23): 2677-2687, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32715955

RESUMEN

Sport-related concussion return to play (RTP) decisions are largely based on the resolution of self-reported symptoms and neurocognitive function. Some evaluators also incorporate balance; however, an objective approach to balance that can detect effects beyond the acute condition is warranted. The purpose of this study is to examine linear measures of biomechanical balance up to 6 months post-concussion, and to present preliminary diagnostic thresholds useful for RTP. Each concussed athlete participated in instrumented standing balance tasks at 4 timepoints post-concussion. The measures from concussed athletes were compared to the sport-matched non-concussed athlete group at each timepoint. Centre of pressure (COP) mediolateral (ML) velocity in double-leg stance on a hard surface discriminated well between non-concussed and concussed athletes. COP anterior-posterior (AP) velocity in tandem stance on foam showed sensitivity to concussion. Sixty per cent of athletes at 6 months post-concussion did not recover to within the proposed COP ML velocity threshold in double-leg stance on a hard surface. Seventy-one per cent of athletes at 6 months post-concussion did not recover to within the COP AP velocity threshold in tandem stance on foam. This lack of recovery potentially indicates vestibular and motor control impairments long past the typical period of RTP.


Asunto(s)
Traumatismos en Atletas/fisiopatología , Conmoción Encefálica/fisiopatología , Equilibrio Postural , Fenómenos Biomecánicos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recuperación de la Función , Volver al Deporte , Posición de Pie , Análisis y Desempeño de Tareas , Adulto Joven
8.
Integr Comp Biol ; 60(2): 385-396, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32492136

RESUMEN

Mechanistically connecting genotypes to phenotypes is a longstanding and central mission of biology. Deciphering these connections will unite questions and datasets across all scales from molecules to ecosystems. Although high-throughput sequencing has provided a rich platform on which to launch this effort, tools for deciphering mechanisms further along the genome to phenome pipeline remain limited. Machine learning approaches and other emerging computational tools hold the promise of augmenting human efforts to overcome these obstacles. This vision paper is the result of a Reintegrating Biology Workshop, bringing together the perspectives of integrative and comparative biologists to survey challenges and opportunities in cracking the genotype to phenotype code and thereby generating predictive frameworks across biological scales. Key recommendations include promoting the development of minimum "best practices" for the experimental design and collection of data; fostering sustained and long-term data repositories; promoting programs that recruit, train, and retain a diversity of talent; and providing funding to effectively support these highly cross-disciplinary efforts. We follow this discussion by highlighting a few specific transformative research opportunities that will be advanced by these efforts.


Asunto(s)
Macrodatos , Biología Computacional/métodos , Código Genético , Genotipo , Fenotipo
9.
Genome Biol Evol ; 12(6): 948-964, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32211845

RESUMEN

Tunicates, the closest living relatives of vertebrates, have served as a foundational model of early embryonic development for decades. Comparative studies of tunicate phylogeny and genome evolution provide a critical framework for analyzing chordate diversification and the emergence of vertebrates. Toward this goal, we sequenced the genome of Corella inflata (Ascidiacea, Phlebobranchia), so named for the capacity to brood self-fertilized embryos in a modified, "inflated" atrial chamber. Combining the new genome sequence for Co. inflata with publicly available tunicate data, we estimated a tunicate species phylogeny, reconstructed the ancestral Hox gene cluster at important nodes in the tunicate tree, and compared patterns of gene loss between Co. inflata and Ciona robusta, the prevailing tunicate model species. Our maximum-likelihood and Bayesian trees estimated from a concatenated 210-gene matrix were largely concordant and showed that Aplousobranchia was nested within a paraphyletic Phlebobranchia. We demonstrated that this relationship is not an artifact due to compositional heterogeneity, as had been suggested by previous studies. In addition, within Thaliacea, we recovered Doliolida as sister to the clade containing Salpida and Pyrosomatida. The Co. inflata genome provides increased resolution of the ancestral Hox clusters of key tunicate nodes, therefore expanding our understanding of the evolution of this cluster and its potential impact on tunicate morphological diversity. Our analyses of other gene families revealed that several cardiovascular associated genes (e.g., BMP10, SCL2A12, and PDE2a) absent from Ci. robusta, are present in Co. inflata. Taken together, our results help clarify tunicate relationships and the genomic content of key ancestral nodes within this phylogeny, providing critical insights into tunicate evolution.


Asunto(s)
Genes Homeobox , Genoma , Filogenia , Urocordados/genética , Animales , Familia de Multigenes
10.
Chiropr Man Therap ; 28(1): 5, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31998472

RESUMEN

Introduction: Manual therapy (MT) hypothetically affects discrepant neuromuscular control and movement observed in populations with low back pain (LBP). Previous studies have demonstrated the limited influence of MT on movement, predominately during range of motion (ROM) testing. It remains unclear if MT affects neuromuscular control in mobility-based activities of daily living (ADLs). The sit-to-stand (STS) task represents a commonly-performed ADL that is used in a variety of clinical settings to assess functional and biomechanical performance. Objective: To determine whether MT affects functional performance and biomechanical performance during a STS task in a population with LBP. Methods: Kinematic data were recorded from the pelvis and thorax of participants with LBP, using an optoelectronic motion capture system as they performed a STS task before and after MT from November 2011 to August 2014. MT for each participant consisted of two high-velocity low-amplitude spinal manipulations, as well as two grade IV mobilizations of the lumbar spine and pelvis targeted toward the third lumbar vertebra and sacroiliac joint in a side-lying position; the order of these treatments was randomized. Pelvis and thorax kinematic data were used to derive the time-varying lumbar angle in the sagittal plane for each STS trial. The difference between the maximum and minimum lumbar angles during the STS trial determined the sagittal ROM that was used as the biomechanical outcome. Time to complete each STS trial was used as a functional measure of performance. Pre-MT and post-MT values for the lumbar sagittal ROM and time to completion were statistically analysed using paired samples t-tests. Results: Data were obtained from 40 participants with 35 useful datasets (NRS = 3.3 ± 1.2; 32.4 ± 9.8 years; 16 females, 19 males). After MT, lumbar sagittal ROM increased by 2.7 ± 5.5 degrees (p = 0.007). Time to complete the STS test decreased by 0.4 ± 0.4 s (p < 0.001). Discussion: These findings provide preliminary evidence that MT might influence the biomechanical and functional performance of an STS task in populations with LBP. The MT intervention in this study involved a combination of spinal manipulations and mobilizations. Future work will expand upon these data as a basis for targeted investigations on the effects of either spinal manipulation and mobilization on neuromuscular control and movement in populations with LBP.


Asunto(s)
Dolor de la Región Lumbar/fisiopatología , Dolor de la Región Lumbar/terapia , Movimiento , Manipulaciones Musculoesqueléticas/métodos , Actividades Cotidianas , Adolescente , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Rango del Movimiento Articular , Adulto Joven
11.
FASEB J ; 34(2): 3359-3366, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31916313

RESUMEN

Possible involvement of complement (C) systems in the pathogenesis of traumatic brain injury (TBI) was investigated by quantifying Cproteins in plasma astrocyte-derived exosomes (ADEs) of subjects with sports-related TBI (sTBI) and TBI in military veterans (mtTBI) without cognitive impairment. All sTBI subjects (n = 24) had mild injuries, whereas eight of the mtTBI subjects had moderate, and 17 had mild injuries. Plasma levels of ADEs were decreased after acute sTBI and returned to normal within months. Cprotein levels in ADEs were from 12- to 35-fold higher than the corresponding levels in neuron-derived exosomes. CD81 exosome marker-normalized ADE levels of classical pathway C4b, alternative pathway factor D and Bb, lectin pathway mannose-binding lectin (MBL), and shared neurotoxic effectors C3b and C5b-9 terminal C complex were significantly higher and those of C regulatory proteins CR1 and CD59 were lower in the first week of acute sTBI (n = 12) than in controls (n = 12). Most C abnormalities were no longer detected in chronic sTBI at 3-12 months after acute sTBI, except for elevated levels of factor D, Bb, and MBL. In contrast, significant elevations of ADE levels of C4b, factor D, Bb, MBL, C3b and C5b-9 terminal C complex, and depressions of CR1 and CD59 relative to those of controls were observed after 1-4 years in early chronic mtTBI (n = 10) and persisted for decades except for normalization of Bb, MBL, and CD59 in late chronic mtTBI (n = 15). Complement inhibitors may be useful therapeutically in acute TBI and post-concussion syndrome.


Asunto(s)
Astrocitos/metabolismo , Lesiones Traumáticas del Encéfalo/sangre , Proteínas del Sistema Complemento/metabolismo , Exosomas/metabolismo , Biomarcadores/sangre , Lesiones Traumáticas del Encéfalo/patología , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Masculino , Adulto Joven
12.
J Man Manip Ther ; 28(2): 94-102, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31829827

RESUMEN

Objectives: This study compares people with recurrent low back pain (rLBP) and people with pre-clinical low back pain (standing-induced low back pain developers; PDs) to each other and back-healthy controls (non-pain developers; NPDs). Movement variability and muscular co-activity related to coordination are important for both rLBP and PDs, and these two groups also have altered static spine extension.Methods: Eleven participants with recurrent low back pain, and twenty-one asymptomatic participants, categorized as PDs (11) and NPDs (10) through an established standing protocol, volunteered for this study. Three phases of standing extension motion (lean, hold, and return to neutral) were analyzed. Root mean square angular jerk was calculated from trunk and pelvis kinematics, co-activation of the trunk and hip musculature were assessed in four-muscle sets.Results: Root-mean-square jerk was greater when returning to neutral than when leaning back during standing extension in all three groups. People with rLBP had reduced co-activity in their trunk extensors, people classified as PD had more co-activity in their hip extensors compared with the other groups, and anterior trunk co-activity was phase-dependent, and similar between groups.Discussion: Movement control alterations with low back pain may start as an over-protective co-activation strategy in those with standing-induced LBP and progress to an under-protective strategy in those with recurrent low back pain. Level of Evidence: 3.


Asunto(s)
Dolor de la Región Lumbar/fisiopatología , Movimiento/fisiología , Contracción Muscular/fisiología , Músculo Esquelético/fisiopatología , Posición de Pie , Torso/fisiopatología , Adulto , Fenómenos Biomecánicos , Electromiografía , Femenino , Humanos , Masculino , Adulto Joven
13.
Nucleic Acids Res ; 48(D1): D668-D675, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31680137

RESUMEN

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.


Asunto(s)
Bases de Datos Genéticas , Perfilación de la Expresión Génica , Genoma , Programas Informáticos , Urocordados/genética , Animales , Sitios de Unión , Cefalocordados/genética , Gráficos por Computador , Simulación por Computador , Equinodermos/genética , Evolución Molecular , Orden Génico , Genómica , Hibridación in Situ , Internet , Anotación de Secuencia Molecular , Filogenia , Lenguajes de Programación , RNA-Seq , Sintenía , Interfaz Usuario-Computador , Vertebrados/genética
14.
J Biomech ; 93: 18-27, 2019 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-31221457

RESUMEN

Lower extremity muscle strength training is a focus of rehabilitation following total hip arthroplasty (THA). Strength of the hip abductor muscle group is a predictor of overall function following THA. The purpose of this study was to investigate the effects of hip abductor strengthening following rehabilitation on joint contact forces (JCFs) in the lower extremity and low back during a high demand step down task. Five THA patients performed lower extremity maximum isometric strength tests and a stair descent task. Patient-specific musculoskeletal models were created in OpenSim and maximum isometric strength parameters were scaled to reproduce measured pre-operative joint torques. A pre-operative forward dynamic simulation of each patient performing the stair descent was constructed using their corresponding patient-specific model to predict JCFs at the ankle, knee, hip, and low back. The hip abductor muscles were strengthened with clinically supported increases (0-30%) above pre-operative values in a probabilistic framework to predict the effects on peak JCFs (99% confidence bounds). Simulated hip abductor strengthening resulted in lower peak JCFs relative to pre-operative for all five patients at the hip (18.9-23.8 ±â€¯16.5%) and knee (20.5-23.8 ±â€¯11.2%). Four of the five patients had reductions at the ankle (7.1-8.5 ±â€¯11.3%) and low back (3.5-7.0 ±â€¯5.3%) with one patient demonstrating no change. The reduction in JCF at the hip joint and at joints other than the hip with hip abductor strengthening demonstrates the dynamic and mechanical interdependencies of the knee, hip and spine that can be targeted in early THA rehabilitation to improve overall patient function.


Asunto(s)
Artroplastia de Reemplazo de Cadera/rehabilitación , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Modelación Específica para el Paciente , Entrenamiento de Fuerza , Anciano , Articulación del Tobillo/fisiología , Femenino , Articulación de la Cadera/fisiología , Humanos , Rodilla , Articulación de la Rodilla/fisiología , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia
15.
FASEB J ; 33(4): 5082-5088, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30605353

RESUMEN

Neuron-derived exosomes (NDEs) were enriched by anti-L1CAM antibody immunoabsorption from plasmas of subjects ages 18-26 yr within 1 wk after a sports-related mild traumatic brain injury (acute mTBI) ( n = 18), 3 mo or longer after the last of 2-4 mTBIs (chronic mTBI) ( n = 14) and with no recent history of TBI (controls) ( n = 21). Plasma concentrations of NDEs, assessed by counts and levels of extracted exosome marker CD81, were significantly depressed by a mean of 45% in acute mTBI ( P < 0.0001), but not chronic mTBI, compared with controls. Mean CD81-normalized NDE levels of a range of functional brain proteins were significantly abnormal relative to those of controls in acute but not chronic mTBI, including ras-related small GTPase 10, 73% decrease; annexin VII, 8.8-fold increase; ubiquitin C-terminal hydrolase L1, 2.5-fold increase; AII spectrin fragments, 1.9-fold increase; claudin-5, 2.7-fold increase; sodium-potassium-chloride cotransporter-1, 2.8-fold increase; aquaporin 4, 8.9-fold increase (3.6-fold increase in chronic mTBI); and synaptogyrin-3, 3.1-fold increase (1.3-fold increase in chronic mTBI) (all acute mTBI proteins P < 0.0001). In chronic mTBI, there were elevated CD81-normalized NDE levels of usually pathologic ß-amyloid peptide 1-42 (1.6-fold, P < 0.0001), P-T181-tau (2.2-fold, P < 0.0001), P-S396-tau (1.6-fold, P < 0.01), IL-6 (16-fold, P < 0.0001), and prion cellular protein (PRPc) (5.1-fold, P < 0.0001) with lesser or greater (IL-6, PRPc) increases in acute mTBI. Increases in NDE levels of most neurofunctional proteins in acute, but not chronic, mTBI, and elevations of most NDE neuropathological proteins in chronic and acute mTBI delineated phase-specificity. Longitudinal studies of more mTBI subjects may identify biomarkers predictive of and etiologically involved in mTBI-induced neurodegeneration.-Goetzl, E. J., Elahi, F. M., Mustapic, M., Kapogiannis, D., Pryhoda, M., Gilmore, A., Gorgens, K. A., Davidson, B., Granholm, A.-C., Ledreux, A. Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury.


Asunto(s)
Conmoción Encefálica/sangre , Exosomas/metabolismo , Neuronas/metabolismo , Adulto , Péptidos beta-Amiloides/metabolismo , Biomarcadores/sangre , Encéfalo/metabolismo , Enfermedad Crónica , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Adulto Joven , Proteínas tau/metabolismo
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 1731-1734, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30440729

RESUMEN

Low back pain is a leading cause of disability, and there is a tremendous need for nonsurgical, nonpharmaceutical interventions to manage it. Versatile spinal exoskeletons have been proposed as a method of supporting or augmenting the wearer, but experimental data from human subjects are limited, and the effects of such exoskeletons remain poorly understood. We thus present a prototype of a reconfigurable spinal exoskeleton that features easily adjustable resistance and compression at multiple spinal levels, allowing us to study the effect of different exoskeleton configurations on the body. In a pilot evaluation with a single subject, both thoracic and abdominal compression were found to affect trunk angle, low back moment and the electromyogram of the erector spinae, though different exoskeleton configurations had different effects during different tasks. This supports the premise that intelligent mechanical adjustments of a spinal exoskeleton are necessary for optimal support or augmentation of the wearer, though the results need to be examined in a larger, varied sample of subjects.


Asunto(s)
Dispositivo Exoesqueleto , Dolor de la Región Lumbar , Columna Vertebral , Adulto , Electromiografía , Dispositivo Exoesqueleto/normas , Humanos , Masculino , Proyectos Piloto , Torso
17.
Foot (Edinb) ; 35: 28-35, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29753998

RESUMEN

BACKGROUND: The intent of this pilot study was to determine the feasibility of using high-speed stereo radiography (HSSR) to assess the effectiveness of footwear and foot orthoses in controlling the change in the position of the midfoot during walking in individuals with a flexible pes planus foot type. METHODS: Four individuals (1 female; 3 male) with a mean age of 25 years (range 22-29) and a bilateral flexible pes planus foot type participated in the study. The HSSR system was used to measure 3-dimensional changes in the longitudinal arch angle (LAA) with each participant walking barefoot, shoe only and shoes with orthoses. RESULTS: The HSSR system was found to be highly effective in measuring the change in the position of the midfoot, as measured using the LAA, when wearing footwear with or without foot orthoses. Based on an assessment of mean values, three out of the four participants demonstrated a change in the LAA as a result of using either shoes only or shoes with orthoses. The methodology used in this pilot study for assessing the effect of footwear and foot orthoses on the posture of the midfoot was highly effective with no side-effects noted by any of the study participants. CONCLUSIONS: Future studies using the HSSR will require modifications to participant inclusion criteria as well as alterations to the data collection methodology. The HSSR system used in this study is feasible for use in larger cohort studies assessing footwear and foot orthosis effectiveness with the described modifications.


Asunto(s)
Pie Plano/diagnóstico por imagen , Pie Plano/rehabilitación , Ortesis del Pié , Radiografía/métodos , Caminata/fisiología , Aceleración , Adulto , Diseño de Equipo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos Piloto , Equilibrio Postural/fisiología , Postura/fisiología , Adulto Joven
18.
J Electromyogr Kinesiol ; 39: 16-25, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29413449

RESUMEN

The objective of this investigation was to identify demands from core muscles that corresponded with trunk movement compensations during bilateral step ambulation in people with unilateral transtibial amputation (TTA). Trunk rotational angular momentum (RAM) was measured using motion capture and bilateral surface EMG was measured from four bilateral core muscles during step ascent and descent tasks in people with TTA and healthy controls. During step ascent, the TTA group generated larger mediolateral (P = 0.01) and axial (P = 0.01) trunk RAM toward the leading limb when stepping onto the intact limb than the control group, which corresponded with high demand from the bilateral erector spinae and oblique muscles. During step descent, the TTA group generated larger trunk RAM in the sagittal (P < 0.01), frontal (P < 0.01), and transverse planes (P = 0.01) than the control group, which was an effect of falling onto the intact limb. To maintain balance and arrest trunk RAM, core muscle demand was larger throughout the loading period of step descent in the TTA group. However, asymmetric trunk movement compensations did not correspond to asymmetric core muscle demand during either task, indicating a difference in motor control compensations dependent on the leading limb.


Asunto(s)
Amputados , Músculo Esquelético/fisiología , Equilibrio Postural , Caminata/fisiología , Accidentes por Caídas , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Torso/fisiología
19.
Clin Biomech (Bristol, Avon) ; 49: 64-71, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28888109

RESUMEN

BACKGROUND: Lower extremity movement compensations following transtibial amputation are well-documented and are likely influenced by trunk posture and movement. However, the biomechanical compensations of the trunk and lower extremities, especially during high-demand tasks such as step ascent and descent, remain unclear. METHODS: Kinematic and kinetic data were collected during step ascent and descent tasks for three groups of individuals: diabetic/transtibial amputation, diabetic, and healthy. An ANCOVA was used to compare peak trunk, hip and knee joint angles and moments in the sagittal and frontal planes between groups. Paired t-tests were used to compare peak joint angles and moments between amputated and intact limbs of the diabetic/transtibial amputation group. FINDINGS: During step ascent and descent, the transtibial amputation group exhibited greater trunk forward flexion and lateral flexion compared to the other two groups (P<0.016), which resulted in greater low back moments and asymmetric loading patterns in the lower extremity joints. The diabetic group exhibited similar knee joint loading patterns compared to the amputation group (P<0.016), during step descent. INTERPRETATION: This study highlights the biomechanical compensations of the trunk and lower extremities in individuals with dysvascular transtibial amputation, by identifying low back, hip, and knee joint moment patterns unique to transtibial amputation during stepping tasks. In addition, the results suggest that some movement compensations may be confounded by the presence of diabetes and precede limb amputation. The increased and asymmetrical loading patterns identified may predispose individuals with transtibial amputation to the development of secondary pain conditions, such as low back pain or osteoarthritis.


Asunto(s)
Amputación Quirúrgica , Extremidad Inferior/fisiopatología , Tibia/cirugía , Torso/fisiopatología , Anciano , Anciano de 80 o más Años , Amputados , Fenómenos Biomecánicos , Femenino , Marcha , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Movimiento , Rango del Movimiento Articular/fisiología
20.
Clin Biomech (Bristol, Avon) ; 48: 88-96, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28797673

RESUMEN

BACKGROUND: Patients with transtibial amputation adopt trunk movement compensations that alter effort and increase the risk of developing low back pain. However, the effort required to achieve high-demand tasks, such as step ascent and descent, remains unknown. METHODS: Kinematics were collected during bilateral step ascent and descent tasks from two groups: 1) seven patients with unilateral transtibial amputation and 2) seven healthy control subjects. Trunk kinetic effort was quantified using translational and rotational segmental moments (time rate of change of segmental angular momentum). Peak moments during the loading period were compared across limbs and across groups. FINDINGS: During step ascent, patients with transtibial amputation generated larger sagittal trunk translational moments when leading with the amputated limb compared to the intact limb (P=0.01). The amputation group also generated larger trunk rotational moments in the frontal and transverse planes when leading with either limb compared to the healthy group (P=0.01, P<0.01, respectively). During step descent, the amputation group generated larger trunk translational and rotational moments in all three planes when leading with the intact limb compared to the healthy group (P<0.017). INTERPRETATION: This investigation identifies how differing trunk movement compensations, identified using the separation of angular momentum, require higher kinetic effort during stepping tasks in patients with transtibial amputation compared to healthy individuals. Compensations that produce identified increased and asymmetric trunk segmental moments, may increase the risk of the development of low back pain in patients with amputation.


Asunto(s)
Amputación Quirúrgica , Columna Vertebral/fisiopatología , Tibia/cirugía , Torso/fisiopatología , Caminata/fisiología , Fenómenos Biomecánicos , Marcha/fisiología , Humanos , Masculino , Persona de Mediana Edad , Equilibrio Postural/fisiología
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