Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to aboveknee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue 1-4 . The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg 5,6 . To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes 7 in the remaining tibial nerve (ClinicalTrials. gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback.Despite advances in the development of lower-limb prosthetics 8 , the potential benefits of restoring sensory feedback from such devices to transfemoral (above-knee) or transtibial (below-knee) amputees has not been investigated. Most surgery techniques 9 and noninvasive methods 10-12 to restore sensory feedback have been tested only in transtibial amputations, which produce a less disabling clinical condition than transfemoral amputation 1,3 . Direct neural stimulation through transversal intrafascicular multichannel electrodes (TIMEs) 7 has enabled upper-limb amputees to feel touch sensations from the missing hand and to exploit them for long-term prosthesis control 13,14 . Only F.M.P. designed the study, developed the software and the overall system integration, performed and supervised the experiments, analyzed the data and wrote and reviewed the paper. M.B. performed the surgeries, was responsible for all the clinical aspects of the study and reviewed the manuscript. G.V. developed the software and the overall system integration, performed the experiments, analyzed the data and reviewed the manuscript. V.I. and S. Mazic collected and analyzed the metabolic measurements. P.M. and B.M. collected and analyzed the EEG measurements. P.C. and T.S. developed the TIME electrodes and delivered technical assistance during the implantation and explanation procedures. F.B. and D.B. developed the software and the overall system integration and performed the experiments. N.K. analyzed the data. D.G. and D.A. designed the hardware and embedded software (real-time control) for STIMEP. K.L. and A.A. participated in the experimental design...
Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.
Bony defects caused by trauma, tumors, infection or congenital anomalies can present a significant surgical challenge. Free vascularised fibular bone grafts (FVFGs) have proven to be extremely effective in managing larger defects (longer than 6 cm) where other conventional grafts have failed. FVFGs also have a role in the treatment of avascular necrosis (AVN) of the femoral head, failed spinal fusions and complex arthrodeses. Due to the fact that they have their own blood supply, FVFGs are effective even in cases where there is poor vascularity at the recipient site, such as in infection and following radiotherapy. This article discusses the versatility of the FVFG and its successful application to a variety of different pathologies. It also covers the applied anatomy, indications, operative techniques, complications and donor-site morbidity. Though technically challenging and demanding, the FVFG is an extremely useful salvage option and can facilitate limb reconstruction in the most complex of cases.
Abstract.Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced concentration-dependent relaxation of rat mesenteric artery. Among the K + -channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K + , the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K + channels and voltage-gated Ca 2+ channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 mM K + in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K + channels. Its ability to completely relax the mesenteric artery precontracted with K + -rich solution suggests that K + channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K + channel-independent effect of resveratrol.
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