Test-retest reliability of the six-minute walking distance measurements using FeetMe insoles by completely unassisted healthy adults in their homes.

Wearable technology provides an opportunity for new ways of monitoring patient gait remotely, through at-home self-administered six-minute walk tests (6MWTs). The purpose of this study was to evaluate the test-retest reliability of FeetMe insoles, a wearable gait assessment device, for measuring the six-minute walking distance (6MWD) during tests conducted with a one-week interval by completely unassisted healthy adults in their homes. Participants (n = 21) performed two 6MWTs at home while wearing the FeetMe insoles, and two 6MWTs at hospital while wearing FeetMe insoles and being assessed by a rater. All assessments were performed with a one-week interval between tests, no assistance was provided to the participants at home. The agreement between the 6MWD measurements made at baseline and at Week 1 was good for all test configurations and was highest for the at-home FeetMe measurements, with an intraclass correlation coefficient (ICC) of 0.95, standard error of the measurement (SEM) of 15.02 m and coefficient of variation (CV) of 3.33%, compared to ICCs of 0.79 and 0.78, SEMs of 25.65 and 26.65 and CVs of 6.24% and 6.10% for the rater and FeetMe measurements at hospital, respectively. Our work demonstrates that the FeetMe system could provide a reliable solution allowing individuals to self-administer 6MWTs independently at home.

Evaluation of the Validity and Reliability of Connected Insoles to Measure Gait Parameters in Healthy Adults.

The continuous, accurate and reliable estimation of gait parameters as a measure of mobility is essential to assess the loss of functional capacity related to the progression of disease. Connected insoles are suitable wearable devices which allow precise, continuous, remote and passive gait assessment. The data of 25 healthy volunteers aged 20 to 77 years were analysed in the study to validate gait parameters (stride length, velocity, stance, swing, step and single support durations and cadence) measured by FeetMe® insoles against the GAITRite® mat reference. The mean values and the values of variability were calculated per subject for GAITRite® and insoles. A t-test and Levene's test were used to compare the gait parameters for means and variances, respectively, obtained for both devices. Additionally, measures of bias, standard deviation of differences, Pearson's correlation and intraclass correlation were analysed to explore overall agreement between the two devices. No significant differences in mean and variance between the two devices were detected. Pearson's correlation coefficients of averaged gait estimates were higher than 0.98 and 0.8, respectively, for unipedal and bipedal gait parameters, supporting a high level of agreement between the two devices. The connected insoles are therefore a device equivalent to GAITRite® to estimate the mean and variability of gait parameters.

FeetMe® Monitor-connected insoles are a valid and reliable alternative for the evaluation of gait speed after stroke.

BACKGROUND: One of the main challenges after stroke is gait recovery. To provide patients with an individualized rehabilitation program, it is helpful to have real-life objective evaluations at baseline and at regular follow-ups to adjust the program and verify potential improvements. OBJECTIVES: To evaluate the accuracy and reliability of a fully stand-alone system of connected insoles (FeetMe® Monitor) against a widely used clinical walkway system (GAITRite®). METHODS: Twenty-nine subjects with a stroke that occurred >6 months prior participated in the study. Their comfortable gait over three 8-m trials was evaluated by four raters, on Day 1 and Day 7, using simultaneously FeetMe® Monitor and GAITRite®. Velocity, stride length, cadence, stance, and swing duration were calculated on both sides over three sequences of gait: one single stride, 8 m, and three 8-m trials pooled. The Intra-class Correlation Coefficient (ICC) and the Bland-Altman plot evaluated the construct validity (inter-device) and the reliability (test-retest and inter-rater) of FeetMe® Monitor. RESULTS: Through all gait analysis sequences, the inter-device ICCs were >0.95 for velocity, stride length, and cadence. Ranges of inter-device ICCs were [0.77-0.94] for stance duration for both limbs, and for swing duration [0.32-0.57] on the non-paretic side and [0.75-0.90] on the paretic side. Test-retest and inter-rater ICCs for all parameters were >0.73 for one single stride, >0.88 for 8-m trials and >0.94 for three 8-m trials. CONCLUSION: FeetMe® Monitor is an accurate and reliable system for measurement of gait velocity, stride length, cadence, and stance duration in chronic hemiparesis.

Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia.

Reactive microgliosis is an important pathological component of neuroinflammation and has been implicated in a wide range of brain diseases including brain tumors, multiple sclerosis, Parkinson's disease, Alzheimer's disease, and schizophrenia. Mapping reactive microglia in-vivo is often performed with PET scanning whose resolution, cost, and availability prevent its widespread use. The advent of diffusion compartment imaging (DCI) to probe tissue microstructure in vivo holds promise to map reactive microglia using MRI scanners. But this potential has never been demonstrated. In this paper, we performed longitudinal DCI in rats that underwent dorsal root axotomy triggering Wallerian degeneration of axons-a pathological process which reliably activates microglia. After the last DCI at 51 days, rats were sacrificed and histology with Iba-1 immunostaining for microglia was performed. The fraction of extra-axonal restricted diffusion from DCI was found to follow the expected temporal dynamics of reactive microgliosis. Furthermore, a strong and significant correlation between this parameter and histological measurement of microglial density was observed. These findings strongly suggest that extra-axonal restricted diffusion is an in-vivo marker of reactive microglia. They pave the way for MRI-based microglial mapping which may be important to characterize the pathogenesis of neurological and psychiatric diseases.

Fibrin hydrogels to deliver dental stem cells of the apical papilla for regenerative medicine.

AIM: Evaluation of survival, proliferation and neurodifferentiation of dental stem cells from the apical papilla (SCAP) in fibrin hydrogels. We hypothesized that fibrin composition will influence cell behavior. METHODS: Modulus, pore and fiber size were measured. SCAP in vitro viability, proliferation and neural differentiation, as well as in vivo proliferation and angiogenesis were studied. RESULTS: Hydrogel moduli were influenced by fibrin formulation but not hydrogel morphology, SCAP in vitro viability and proliferation. In total 60% of SCAP expressed PanNeurofilament in vitro without induction in Fibrinogen50-Thrombin10. SCAP proliferated when implanted in vivo and stimulated host endothelial cell infiltration. CONCLUSION: Fibrinogen30-Thrombin10 or Thrombin50 would be more favorable to in vitro SCAP viability and in vivo proliferation, while Fibrinogen 50-Thrombin50 would be more adapted to neurodifferentiation.

Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy.

Multifunctional nanoparticles combining therapy and imaging have the potential to improve cancer treatment by allowing personalized therapy. Herein, we aimed to compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of αvß3 integrin via RGD grafting, (3) magnetic targeting via a magnet placed on the tumor and (4) the combination of magnetic targeting and active targeting of αvß3 integrin. For a translational approach, PLGA-based nanoparticles loaded with paclitaxel and superparamagnetic iron oxides were used. Electron Spin Resonance spectroscopy and Magnetic Resonance Imaging (MRI) were used to both quantify and visualize the accumulation of multifunctional nanoparticles into the tumors. We demonstrate that compared to untargeted or single targeted nanoparticles, the combination of both active strategy and magnetic targeting drastically enhanced (i) nanoparticle accumulation into the tumor tissue with an 8-fold increase compared to passive targeting (1.12% and 0.135% of the injected dose, respectively), (ii) contrast in MRI (imaging purpose) and (iii) anti-cancer efficacy with a median survival time of 22 days compared to 13 for the passive targeting (therapeutic purpose). Double targeting of nanoparticles to tumors by different mechanisms could be a promising translational approach for the management of therapeutic treatment and personalized therapy.

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury.

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low ßIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.