17ß-Estradiol Effects in Skeletal Muscle: A 31P MR Spectroscopic Imaging (MRSI) Study of Young Females during Early Follicular (EF) and Peri-Ovulation (PO) Phases.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17ß-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17ß-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17ß-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17ß-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17ß-estradiol suggests that 17ß-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

Myoelectric interface for neurorehabilitation conditioning to reduce abnormal leg co-activation after stroke: a pilot study.

BACKGROUND: The ability to walk is an important factor in quality of life after stroke. Co-activation of hip adductors and knee extensors has been shown to correlate with gait impairment. We have shown previously that training with a myoelectric interface for neurorehabilitation (MINT) can reduce abnormal muscle co-activation in the arms of stroke survivors. METHODS: Here, we extend MINT conditioning to stroke survivors with leg impairment. The aim of this pilot study was to assess the safety and feasibility of using MINT to reduce abnormal co-activation between hip adductors and knee extensors and assess any effects on gait. Nine stroke survivors with moderate to severe gait impairment received 6 h of MINT conditioning over six sessions, either in the laboratory or at home. RESULTS: MINT participants completed a mean of 159 repetitions per session without any adverse events. Further, participants learned to isolate their muscles effectively, resulting in a mean reduction of co-activation of 70% compared to baseline. Moreover, gait speed increased by a mean of 0.15 m/s, more than the minimum clinically important difference. Knee flexion angle increased substantially, and hip circumduction decreased. CONCLUSION: MINT conditioning is safe, feasible at home, and enables reduction of co-activation in the leg. Further investigation of MINT's potential to improve leg movement and function after stroke is warranted. Abnormal co-activation of hip adductors and knee extensors may contribute to impaired gait after stroke. Trial registration This study was registered at ClinicalTrials.gov (NCT03401762, Registered 15 January 2018, https://clinicaltrials.gov/study/NCT03401762?tab=history&a=4 ).

Oral Contraception Use and Musculotendinous Injury in Young Female Patients: A Database Study.

PURPOSE: The purpose of this study is to characterize the effect of sex and the influence of oral contraception usage on musculotendinous injury (MTI). Current literature suggests a disparity in the incidence of MTI between males and females. This may be attributed to inherent biological differences between the sexes, such as in the sex hormonal milieu. There is a lack of information associating sex hormone milieu and MTI. METHODS: We searched the PearlDiver database (a for-fee healthcare database) for males, females taking oral contraceptives (OC), and eumenorrheic females not taking any form of hormonal contraceptives (non-OC) 18-39 yr old. The three populations were matched by age and body mass index. We queried the database for lower-extremity skeletal MTI diagnoses in these groups. RESULTS: Each group contained 42,267 patients with orthopedic injuries. There were a total of 1476 (3.49%) skeletal MTI in the male group, 1078 (2.55%) in non-OC females, and 231 (0.55%) in OC females. Both the non-OC and the OC groups had a significantly smaller proportion of MTI than males ( P < 0.0001), and therefore these groups were less likely (adjusted odds ratios, 0.72 and 0.15, respectively) to experience MTI when controlled for potential covariates. CONCLUSIONS: In this study, we show that females are less likely to develop MTI to total injuries, when compared with males, with OC using females being least likely followed by non-OC females. These results are consistent with other epidemiological studies; however, overall results in the literature are variable. This study adds to the emerging body of literature on sex hormone-influenced musculoskeletal injury but, more specifically, MTI, which have not been rigorously investigated.

Myoelectric interface for neurorehabilitation conditioning to reduce abnormal leg co-activation after stroke: a pilot study.

Background: The ability to walk is an important factor in quality of life after stroke. Co-activation of hip adductors and knee extensors has been shown to correlate with gait impairment. We have shown previously that training with a myoelectric interface for neurorehabilitation (MINT) can reduce abnormal muscle co-activation in the arms of stroke survivors. Methods: Here, we extend MINT conditioning to stroke survivors with leg impairment. The aim of this pilot study was to assess the safety and feasibility of using MINT to reduce abnormal co-activation between hip adductors and knee extensors and assess any effects on gait. Nine stroke survivors with moderate to severe gait impairment received six hours of MINT conditioning over six sessions, either in the laboratory or at home. Results: MINT participants completed a mean of 159 repetitions per session without any adverse events. Further, participants learned to isolate their muscles effectively, resulting in a mean reduction of co-activation of 70% compared to baseline. Moreover, gait speed increased by a mean of 0.15 m/s, more than the minimum clinically important difference. Knee flexion angle increased substantially, and hip circumduction decreased. Conclusion: MINT conditioning is safe, feasible at home, and enables reduction of co-activation in the leg. Further investigation of MINT's potential to improve leg movement and function after stroke is warranted. Abnormal co-activation of hip adductors and knee extensors may contribute to impaired gait after stroke. Trial registration: This study was registered at ClinicalTrials.gov (NCT03401762, Registered 15 January 2018, https://clinicaltrials.gov/study/NCT03401762?tab=history&a=4).

Identifying spinal tracts transmitting distant effects of trans-spinal magnetic stimulation.

Estimating the state of tract-specific inputs to spinal motoneurons is critical to understanding movement deficits induced by neurological injury and potential pathways to recovery but remains challenging in humans. In this study, we explored the capability of trans-spinal magnetic stimulation (TSMS) to modulate distal reflex circuits in young adults. TSMS was applied over the thoracic spine to condition soleus H-reflexes involving sacral-level motoneurons. Three TSMS intensities below the motor threshold were applied at interstimulus intervals (ISIs) between 2 and 20 ms relative to peripheral nerve stimulation (PNS). Although low-intensity TSMS yielded no changes in H-reflexes across ISIs, the two higher stimulus intensities yielded two phases of H-reflex inhibition: a relatively long-lasting period at 2- to 9-ms ISIs, and a short phase at 11- to 12-ms ISIs. H-reflex inhibition at 2-ms ISI was uniquely dependent on TSMS intensity. To identify the candidate neural pathways contributing to H-reflex suppression, we constructed a tract-specific conduction time estimation model. Based upon our model, H-reflex inhibition at 11- to 12-ms ISIs is likely a manifestation of orthodromic transmission along the lateral reticulospinal tract. In contrast, the inhibition at 2-ms ISI likely reflects orthodromic transmission along sensory fibers with activation reaching the brain, before descending along motor tracts. Multiple pathways may contribute to H-reflex modulation between 4- and 9-ms ISIs, orthodromic transmission along sensorimotor tracts, and antidromic transmission of multiple motor tracts. Our findings suggest that noninvasive TSMS can influence motoneuron excitability at distal segments and that the contribution of specific tracts to motoneuron excitability may be distinguishable based on conduction velocities.NEW & NOTEWORTHY This study explored the capability of trans-spinal magnetic stimulation (TSMS) over the thoracic spine to modulate distal reflex circuits, H-reflexes involving sacral-level motoneurons, in young adults. TSMS induced two inhibition phases of H-reflex across interstimulus intervals (ISIs): a relatively long-lasting period at 2- to 9-ms ISIs, and a short phase at 11- to 12-ms ISIs. An estimated probability model constructed from tract-specific conduction velocities allowed the identification of potential spinal tracts contributing to the changes in motoneuron excitability.

Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading.

OBJECTIVE: Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints. DESIGN: Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-ß, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP). RESULTS: Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1ß, TNF-α, IL-10, and TGF-ß from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint. CONCLUSION: Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.

Sex hormone-mediated change on muscle activation deactivation dynamics in young eumenorrheic women.

The goal of the study was to characterize muscle activation/deactivation dynamics across the menstrual cycle in healthy young women. Twenty-two healthy eumenorrheic women (age: 27.0 ± 4.4 years; mean ± SD) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were quantified at the time of testing. Peak torque (PT), time to peak torque (TPT), and half relaxation time (HRT) of soleus muscle twitch were measured. Muscle twitch was elicited by delivering 1 ms width electrical pulses to the tibial nerve at an intensity that generated a maximum motor response (S-100) and at supramaximal intensity (S-120; 1.2 × S-100). The analyses were performed for each menstrual cycle phase: 1) the follicular phase to analyze the effect of estradiol while the progesterone concentrations remained at low concentrations; 2) the luteal phase to analyze the effect of progesterone with background estradiol concentrations. In the follicular phase, there was no association of estradiol for PT, TPT, and HRT. In the luteal phase, while estradiol had no association on PT, TPT, and HRT, progesterone expressed a significant association with HRT reduction but no association on PT or TPT. Also, there was a significant estradiol and progesterone interaction for HRT. However, the regression parameters are nearly zero, suggesting that the change in HRT may not have an impact on muscle performance across the menstrual cycle but implications on other women's health conditions with elevated sex hormone concentrations, such as pregnancy, may prove critical.

Surrogate modeling of articular cartilage degradation to understand the synergistic role of MMP-1 and MMP-9: a case study.

A characteristic feature of arthritic diseases is cartilage extracellular matrix (ECM) degradation, often orchestrated by the overexpression of matrix metalloproteinases (MMPs) and other proteases. The interplay between fibril level degradation and the tissue-level aggregate response to biomechanical loading was explored in this work by a computational multiscale cartilaginous model. We considered the relative abundance of collagenases (MMP-1) and gelatinases (MMP-9) in surrogate models, where the diffusion (spatial distribution) of these enzymes and the subsequent, co-localized fibrillar damage were spatially randomized with Latin Hypercube Sampling. The computational model was constructed by incorporating the results from prior molecular dynamics simulations (tensile test) of microfibril degradation into a hyper-elastoplastic fibril-reinforced cartilage model. Including MMPs-mediated collagen fibril-level degradation in computational models may help understand the ECM pathomechanics at the tissue level. The mechanics of cartilage tissue and fibril show variations in mechanical integrity depending on the different combinations of MMPs-1 and 9 with a concentration ratio of 1:1, 3:1, and 1:3 in simulated indentation tests. The fibril yield (local failure) was initiated at 20.2 ± 3.0 (%) and at 23.0 ± 2.8 (%) of bulk strain for col 1:gel 3 and col 3: gel 1, respectively. The reduction in failure stress (global response) was 39.8% for col 1:gel 3, 37.5% for col 1:gel 1, and 36.7% for col 3:gel 1 compared with the failure stress of the degradation free tissue. These findings indicate that cartilage's global and local mechanisms of failure largely depend on the relative abundance of the two key enzymes-collagenase (MMP-1) and gelatinase (MMP-9) and the spatial characteristics of diffusion across the layers of the cartilage ECM.

Sex hormone mediated change on flexion reflex.

It has been shown that estrogen and progesterone receptors are expressed in the spinal cord; therefore, fluctuation in their concentrations may affect the spinal network and modulate the control of movement. Herein, we assessed the neuro-modulatory effect of sex hormones on the polysynaptic spinal network by using a flexion reflex network as a model system. Twenty-four healthy eumenorrheic women (age 21-37 years) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were acquired at the time of testing. The flexion reflex of the tibialis anterior was elicited by sending an innocuous electrical stimulus directly to the posterior tibial nerve or plantar cutaneous afferent. Analyses were performed for each menstrual cycle phase: the follicular phase and the luteal phase. Increases in estradiol or progesterone concentrations were not associated with reflex duration or root mean squared (RMS) amplitude in either the follicular or luteal phases. In the luteal phase, an increase in the estradiol concentration was associated with a longer latency of the reflex (b = 0.23, p = 0.038). The estradiol × progesterone interaction was found towards significance (b = -0.017, p = 0.081). These results highlight the potential synergistic effect of estradiol and progesterone and may provide indirect confirmatory evidence of the observed modulatory effect.

Can Increased Locomotor Task Difficulty Differentiate Knee Muscle Forces After Anterior Cruciate Ligament Reconstruction?

Changes in knee mechanics following anterior cruciate ligament (ACL) reconstruction are known to be magnified during more difficult locomotor tasks, such as when descending stairs. However, it is unclear if increased task difficulty could distinguish differences in forces generated by the muscles surrounding the knee. This study examined how knee muscle forces differ between individuals with ACL reconstruction with different graft types (hamstring tendon and patellar tendon autograft) and "healthy" controls when performing tasks with increasing difficulty. Dynamic simulations were used to identify knee muscle forces in 15 participants when walking overground and descending stairs. The analysis was restricted to the stance phase (foot contact through toe-off), yielding 162 separate simulations of locomotion in increasing difficulty: overground walking, step-to-floor stair descent, and step-to-step stair descent. Results indicated that knee muscle forces were significantly reduced after ACL reconstruction, and stair descent tasks better discriminated changes in the quadriceps and gastrocnemii muscle forces in the reconstructed knees. Changes in quadriceps forces after a patellar tendon graft and changes in gastrocnemii forces after a hamstring tendon graft were only revealed during stair descent. These results emphasize the importance of incorporating sufficiently difficult tasks to detect residual deficits in muscle forces after ACL reconstruction.

Sensitivity analysis of the knee ligament forces to the surgical design variation during anterior cruciate ligament reconstruction: a finite element analysis.

The purpose of this study is to understand the effect of essential surgical design parameters on collateral and cruciate ligaments behavior for a Bone-Patellar-Tendon-Bone (BPTB) anterior cruciate ligament reconstruction (ACL-R) surgery. A parametric finite element model of biomechanical experiments depicting the ACL-R surgery associated with a global sensitivity analysis was adopted in this work. The model parameters were six intraoperative variables, two-quadrant coordinates of femoral tunnel placement, femoral tunnel sagittal and coronal angles, graft pretension, and the joint angle at which the BPTB graft is tensioned (fixation angle). Our results indicated that cruciate ligaments (posterior cruciate ligament (PCL) and graft) were mainly sensitive to graft pretension (23%), femoral tunnel sites (56%), and the angle at which the surgeon decided to fix the graft (14%). The collateral ligaments (medial and lateral) were also affected by the same set of surgical parameters as the cruciate ligaments except for graft pretension. The output data of this study may help to identify a better role for the ACL-R intraoperative variables in optimizing the knee joint ligaments' postsurgical functionality.

Computational frame of ligament in situ strain in a full knee model.

The biomechanical function of connective tissues in a knee joint is to stabilize the kinematics-kinetics of the joint by augmenting its stiffness and limiting excessive coupled motion. The connective tissues are characterized by an in vivo reference configuration (in situ strain) that would significantly contribute to the mechanical response of the knee joint. In this work, a novel iterative method for computing the in situ strain at reference configuration was presented. The framework used an in situ strain gradient approach (deformed reference configuration) and a detailed finite element (FE) model of the knee joint. The effect of the predicted initial configuration on the mechanical response of the joint was then investigated under joint axial compression, passive flexion, and coupled rotations (adduction and internal), and during the stance phase of gait. The inclusion of the reference configuration has a minimal effect on the knee joint mechanics under axial compression, passive flexion, and at two instances (0% and 50%) of the stance phase of gait. However, the presence of the ligaments in situ strains significantly increased the joint stiffness under passive adduction and internal rotations, as well as during the other simulated instances (25%, 75% and 100%) of the stance phase of gait. Also, these parameters substantially altered the local loading state of the ligaments and resulted in better agreement with the literature during joint flexion. Therefore, the proposed computational framework of ligament in situ strain will help to overcome the challenges in considering this crucial biological aspect during knee joint modeling. Besides, the current construct is advantageous for a better understanding of the mechanical behavior of knee ligaments under physiological and pathological states and provide relevant information in the design of reconstructive treatments and artificial grafts.

In-Vivo Study of Passive Musculotendon Mechanics in Chronic Hemispheric Stroke Survivors.

We characterized the passive mechanical properties of the affected and contralateral musculotendon units in 9 chronic stroke survivors as well as in 6 neurologically-intact controls. Using a position-controlled motor, we precisely indented the distal tendon of the biceps brachii to a 20 mm depth from skin, recording both its sagittal motion using ultrasound movies and the compression force at the tip of the indenter. Length changes of 8 equally-spaced features along the aponeurosis axis were quantified using a pixel-tracking protocol. We report that, on the aggregate and with respect to contralateral and control, respectively, the affected side initiates feature motion at a shorter indentation distance by 61% and 50%, travels further by 15% and 9%, at a lower rate of 28% and 15%, and is stiffer by 40% and 57%. In an extended analysis including the spatial location of the 8 designated features, we report that in contrast to the contralateral and control muscles, the affected musculotendon unit does not strain measurably within the imaging window. These results confirm that chronic stroke-induced spasticity changes musculotendon unit passive mechanics, causing it to not strain under stretch. The mechanisms responsible for altered passive mechanics may lie within extracellular matrix fibrosis.

A multiscale synthesis: characterizing acute cartilage failure under an aggregate tibiofemoral joint loading.

Knee articular cartilage is characterized by a complex mechanical behavior, posing a challenge to develop an efficient and precise model. We argue that the cartilage damage, in general, can be traced to the fibril level as a plastic deformation, defined as micro-defects. To investigate these micro-defects, we have developed a detailed finite element model of the entire healthy tibiofemoral joint (TF) including a multiscale constitutive model which considers the structural hierarchies of the articular cartilage. The net model was simulated under physiological loading conditions to predict joint response under 2000 N axial compression and damage initiation under high axial loading (max 7 KN) when the TF joint flexed to 30°. Computed results sufficiently agreed with earlier experimental and numerical studies. Further, initiation and propagation of damage in fibrils were computed at the tibial cartilage located mainly in the superficial and middle layers. Our simulation results also indicated that the stiffer the fibril is (higher cross-link densities), the higher the contact stress required to elicit a fibril yield and the higher the rate of yielding as a function of increased contact stress. To the best of our knowledge, this is the first model that combines macro-continuum joint mechanics and micromechanics at the tissue level. The computational construct presented here serves as a simulation platform to explore the interplay between acute cartilage damage and micromechanics characteristics at the tropocollagen level.

The effect of fibrillar degradation on the mechanics of articular cartilage: a computational model.

The pathogenesis and pathophysiological underpinnings of cartilage degradation are not well understood. Either mechanically or enzymatically mediated degeneration at the fibril level can lead to acute focal injuries that will, overtime, cause significant cartilage degradation. Understanding the relationship between external loading and the basic molecular structure of cartilage requires establishing a connection between the fibril-level defects and its aggregate effect on cartilage. In this work, we provide a multiscale constitutive model of cartilage to elucidate the effect of two plausible fibril degradation mechanisms on the aggregate tissue: tropocollagen crosslink failure (ß) and a generalized surface degradation (δ). Using our model, the mechanics of aggregate tissue shows differed yield stress and post-yield behavior after crosslink failure and surface degradation compared to intact cartilage, and the tissue-level aggregate behaviors are different from the fibrillar behaviors observed in the molecular dynamics simulations. We also compared the effect of fibrillar defects in terms of crosslink failure and surface degradation in different layers of cartilage within the macroscale tissue construct during a simulated nanoindentation test. Although the mechanical properties of cartilage tissue were largely contingent upon the mechanical properties of the fibril, the macroscale mechanics of cartilage tissue showed ~ 10% variation in yield strain (tissue yield strain: ~ 27 to ~ 37%) compared to fibrillar yield strain (fibrillar yield strain: ~ 16 to ~ 26%) for crosslink failure and ~ 7% difference for the surface degradation (yield strain variations at the tissue: ~ 30 to ~ 37% and fibril: ~ 24 to ~ 26%) at the superficial layer. The yield strain was further delayed in middle layers at least up to 30% irrespective of the failure mechanisms. The cartilage tissue appeared to withstand more strain than the fibrils. The degeneration mechanisms of fibril differentially influenced the aggregate mechanics of cartilage, and the deviation may be attributed to fiber-matrix interplay, depth-dependent fiber orientation and fibrillar defects with different degradation mechanisms. The understanding of the aggregate stress-strain behavior of cartilage tissue, cartilage degradation and its underlying biomechanical factors is important for developing engineering approaches and therapeutic interventions for cartilage pathologies.

Vastus lateralis and vastus medialis produce distinct mediolateral forces on the patella but similar forces on the tibia in the rat.

Improper activation of the quadriceps muscles vastus medialis (VM) and vastus lateralis (VL) has been implicated in the development of patellofemoral pain (PFP). This explanation of PFP assumes that VM and VL produce opposing mediolateral forces on the patella. Although studies have provided evidence for opposing actions of VM and VL on the patella, other studies have suggested that their actions might be similar. In this study, we took advantage of the experimental accessibility of the rat to directly measure the forces on the patella produced by VM and VL. We found that VM and VL produce opposing mediolateral forces on the patella when the patella was lifted away from the femur. These distinct mediolateral forces were not transmitted to the tibia, however: forces measured at the distal tibia were very similar for VM and VL. Further, when the patella was placed within the trochlear groove, the forces on the patella produced by VM and VL were very similar to one another. These results suggest that mediolateral forces produced by VM and VL are balanced by reaction forces from the trochlear groove and so are not transmitted to the tibia. These results provide a rich characterization of the mechanical actions of VM and VL and have implications about the potential role of these muscles in PFP and their neural control during behavior.

Manipulating post-stroke gait: Exploiting aberrant kinematics.

Post-stroke individuals often exhibit abnormal kinematics, including increased pelvic obliquity and hip abduction coupled with reduced knee flexion. Prior examinations suggest these behaviors are expressions of abnormal cross-planar coupling of muscle activity. However, few studies have detailed the impact of gait-retraining paradigms on three-dimensional joint kinematics. In this study, a cross-tilt walking surface was examined as a novel gait-retraining construct. We hypothesized that relative to baseline walking kinematics, exposure to cross-tilt would generate significant changes in subsequent flat-walking joint kinematics during affected limb swing. Twelve post-stroke participants walked on a motorized treadmill platform during a flat-walking condition and during a 10-degree cross-tilt with affected limb up-slope, increasing toe clearance demand. Individuals completed 15 min of cross-tilt walking with intermittent flat-walking catch trials and a final washout period (5 min). For flat-walking conditions, we examined changes in pelvic obliquity, hip abduction/adduction and knee flexion kinematics at the spatiotemporal events of swing initiation and toe-off, and the kinematic event of maximum angle during swing. Pelvic obliquity significantly reduced at swing initiation and maximum obliquity in the final catch trial and late washout. Knee flexion significantly increased at swing initiation, toe-off, and maximum flexion across catch trials and late washout. Hip abduction/adduction was not significantly influenced following cross-tilt walking. Significant decrease in the rectus femoris and medial hamstrings muscle activity across catch trials and late washout was observed. Exploiting the abnormal features of post-stroke gait during retraining yielded desirable changes in muscular and kinematic patterns post-training.

In silico study of principal sex hormone effects on post-injury synovial inflammatory response.

Following an anterior cruciate ligament injury, premenopausal females tend to experience poorer outcomes than males, and sex hormones are thought to contribute to the disparity. Evidence seems to suggest that the sex hormones estrogen, progesterone, and testosterone may regulate the inflammation caused by macrophages, which invade the knee after an injury. While the individual effects of hormones on macrophage inflammation have been studied in vitro, their combined effects on post-injury inflammation in the knee have not been examined, even though both males and females have detectable levels of both estrogen and testosterone. In the present work, we developed an in silico kinetic model of the post-injury inflammatory response in the human knee joint and the hormonal influences that may shape that response. Our results indicate that post-injury, sex hormone concentrations observed in females may lead to a more pro-inflammatory, catabolic environment, while the sex hormone concentrations observed in males may lead to a more anti-inflammatory environment. These findings suggest that the female hormonal milieu may lead to increased catabolism, potentially worsening post-injury damage to the cartilage for females compared to males. The model developed herein may inform future in vitro and in vivo studies that seek to uncover the origins of sex differences in outcomes and may ultimately serve as a starting point for developing targeted therapies to prevent or reduce the cartilage damage that results from post-injury inflammation, particularly for females.

Contralesional Hemisphere Regulation of Transcranial Magnetic Stimulation-Induced Kinetic Coupling in the Poststroke Lower Limb.

BACKGROUND: The neural constraints underlying hemiparetic gait dysfunction are associated with abnormal kinetic outflow and altered muscle synergy structure. Recent evidence from our lab implicates the lesioned hemisphere in mediating the expression of abnormally coupled hip adduction and knee extension synergy, suggesting a role of cortical networks in the regulation of lower limb motor outflow poststroke. The potential contribution of contralesional hemisphere (CON-H) in regulating paretic leg kinetics is unknown. The purpose of this study is to characterize the effect of CON-H activation on aberrant across-joint kinetic coupling of the ipsilateral lower-extremity muscles poststroke. METHODS: Amplitude-matched adductor longus motor-evoked potentials were elicited using single pulse transcranial magnetic stimulation (TMS) of the lesioned (L-H) and CON-Hs during an isometric adductor torque matching task from 11 stroke participants. For 10 control participants, TMS of the contralateral and ipsilateral hemisphere were given during the same task. TMS-induced torques were characterized at the hip and knee joints to determine the differential regulation of abnormal kinetic synergies by each motor cortices. The TMS-induced ratio of knee extension/hip adduction torques was quantified during 40 and 20% of maximum adduction torque. FINDINGS: For both the 40 and 20% target adduction tasks, we find that contralesional stimulation significantly reduced but did not eliminate the TMS-induced ratio of knee extension/hip adduction torques for the stroke group (p = 0.0468, p = 0.0396). In contrast, the controls did not present a significantly different TMS-evoked torque following stimulation (p = 0.923) of the hemisphere ipsilateral to the test leg. INTERPRETATION: The reduced expression of abnormal across-joint kinetic coupling suggests that the CON-H may contribute an adaptive role in lower limb control poststroke. Future study of neuromodulation paradigms that leverage adaptive CON-H activation may yield clinically relevant gains in lower limb motor function poststroke.