Smart Protocols for Physical Therapy of Foot Drop Based on Functional Electrical Stimulation: A Case Study

Functional electrical stimulation (FES) is used for treating foot drop by delivering electrical pulses to the anterior tibialis muscle during the swing phase of gait. This treatment requires that a patient can walk, which is mostly possible in the later phases of rehabilitation. In the early phase of recovery, the therapy conventionally consists of stretching exercises, and less commonly of FES delivered cyclically. Nevertheless, both approaches minimize patient engagement, which is inconsistent with recent findings that the full rehabilitation potential could be achieved by an active psycho-physical engagement of the patient during physical therapy. Following this notion, we proposed smart protocols whereby the patient sits and ankle movements are FES-induced by self-control. In six smart protocols, movements of the paretic ankle were governed by the non-paretic ankle with different control strategies, while in the seventh voluntary movements of the paretic ankle were used for stimulation triggering. One stroke survivor in the acute phase of recovery participated in the study. During the therapy, the patient’s voluntary ankle range of motion increased and reached the value of normal gait after 15 sessions. Statistical analysis did not reveal the differences between the protocols in FES-induced movements.The APC was funded by Lund University Librar

The role of distributed electrical stimulation in rehabilitation after stroke

Функционална електрична стимулација (ФЕС) је метод спољашњег генерисања функционалних покрета електричним импулсима. Побуђивањем нервних влакана ФЕС индиректно активира парализоване мишиће и аферентне путеве, чиме доприноси пластичности нервног система. Овај ефекат је значајан и он је допринео да ФЕС технологија постане важан елемент неурорехабилитације пацијената после можданог удара. У терапији предност имају ФЕС уређаји који користе површинске електроде, јер су ови системи неинвазивни. Недостатак површинских ФЕС уређаја је недовољна селективност активације парализованих мишића. Ова теза приказује проблем и наше оригинално решење новог ФЕС система који користи нови тип електрода које имају више проводних контаката са кожом, a са циљем поузданог генерисања жељених покрета у скочном зглобу пацијената после можданог удара. Теза приказује и резултате нове методе проналажења оптималне стимулационе шеме. Представљен је алгоритам који аутоматски класификује покрете индуковане ФЕС-ом на основу специјално развијеног сензора, који је део новог ФЕС система. Исти сензор се користи за контролу дефинисаних стимулационих шема у реалном времену у различитим фазама хода, што је унапређење у односу на постојеће ФЕС системе. Развијено управљање стимулационим шемама омогућује кинетику асистираног хода веома сличну кинетици нормалног хода. Значајан елемент у овом истраживању је проучавање ефеката терапије при примени новог ФЕС уређаја у клиничким условима. Студије су укључиле пацијенте са падајућим стопалом који је последица можданог удара. Поменути нови сензорски система омогућио је анализу параметара хода (брзина хода, дужина и трајање корака и појединих фаза хода, симетрија, итд.). Део истраживања је био везан за развој протокола примене новог ФЕС система за неамбулаторне пацијенте. ФЕС систем који смо развили помаже вољне покрете у скочном зглобу паретичне ноге пацијента који седи. Погодност овакве терапије је активно ангажовање пацијената у раној фази након можданог удара што убрзава опоравак.Functional electrical stimulation (FES) is a method for the external generation of functional movements by electrical pulses. By nerve fibers excitation, FES indirectly activates paralyzed muscles and afferent pathways, thus contributing to the plasticity of the nervous system. This effect is significant and it has contributed to the fact that FES technology has become an important element of neurorehabilitation of patients after stroke. In therapy, FES devices that use surface electrodes are preferred because these systems are non-invasive. The disadvantage of surface FES devices is the insufficient selectivity of paralyzed muscle activation. This thesis illustrates the problem and our original solution based on a new FES system that uses a new type of electrodes that have multiple conductive contacts with the skin to reliably generate desired ankle joint movements of stroke survivors. The thesis also shows the results of the new method for finding the optimal stimulation schemes. The presented algorithm automatically classifies FES-induced movements based on a specially developed sensor, that is a part of the new FES system. The same sensor is used to control the defined stimulation schemes in real-time during different gait phases, which is an improvement over existing FES systems. The developed control of stimulation schemes results in the similarity between the kinetics of the assisted gait and a normal gait. A significant element of this research is the evaluation of the effects of the therapy that is based on the new FES device in clinic. The studies have included the patients with foot drop caused by stroke. The aforementioned new sensory system enabled the analysis of gait parameters (gait velocity, length and duration of steps and individual gait phases, symmetry, etc.). A part of the research was the development of a protocol for using the new FES system for non-ambulatory patients. The developed FES system assisted voluntary movements of the ankle joint while the patient was seated. The benefit of this type of therapy is the active involvement of patients at an early stage recovery after stroke which speeds up recovery

Optimization of Semiautomated Calibration Algorithm of Multichannel Electrotactile Feedback for Myoelectric Hand Prosthesis

The main drawback of the commercially available myoelectric hand prostheses is the absence of somatosensory feedback. We recently developed a feedback interface for multiple degrees of freedom myoelectric prosthesis that allows proprioceptive and sensory information (i.e., grasping force) to be transmitted to the wearer instantaneously. High information bandwidth is achieved through intelligent control of spatiotemporal distribution of electrical pulses over a custom-designed electrode array. As electrotactile sensations are location-dependent and the developed interface requires that electrical stimuli are perceived to be of the same intensity on all locations, a calibration procedure is of high importance. The aim of this study was to gain more insight into the calibration procedure and optimize this process by leveraging a priori knowledge. For this purpose, we conducted a study with 9 able-bodied subjects performing 10 sessions of the array electrode calibration. Based on the collected data, we optimized and simplified the calibration procedure by adapting the initial (baseline) amplitude values in the calibration algorithm. The results suggest there is an individual pattern of stimulation amplitudes across 16 electrode pads for each subject, which is not affected by the initial amplitudes. Moreover, the number of user actions performed and the time needed for the calibration procedure are significantly reduced by the proposed methodology.The research was supported by Tecnalia Research & Innovation, Spain, and the Ministry of Education, Science and Technological Development of Republic of Serbia (Project no. 175016). The authors would like to thank all the volunteers who participated in this study

LACTONASE MEDIATED QUORUM QUENCHING OF PSEUDOMONAS AERUGINOSA VIRULENCE

Solving the problem of the antimicrobial resistance crisis is one of the primary challenges currently confronting the healthcare system. One of the most promising new strategies to combat antimicrobial resistance is the antivirulence therapy, based on silencing bacterial cell-to-cell communication (quorum quenching - QQ). QQ enzymes lactonases represent a diverse group of enzymes capable of inactivating signaling molecules of bacterial communication – N-acyl homoserine lactones (AHLs), resulting in alterations ofbacterial virulence. The numerous virulence factors and resistance to most conventional antibiotics have led to Pseudomonas aeruginosa being listed as one of the top-priority pathogens on the ESCAPE pathogen list, highlighting the urgent need for the development of new therapies to combat this pathogen. P. aeruginosauses cell-to-cell communication known as quorum sensing (QS) that allows bacteria to monitor their own population density via signal molecules and subsequently control bacterial pathogenesis. Our hypothesis was that bacterial pathogens which share the same ecological niche with P. aeruginosa during infection have developed a system to disrupt its QS system, in order to survive in polymicrobial communities alongside this successful pathogen. In our research we identified QQ enzymes lactonases originating from two Gramnegative bacterial pathogens Burkholderiacepacia and Stenotrophomonas maltophilia. The genes encoding for the enzymes were cloned and expressed in pQE30 expression vector. B. cepacia BCC4135 synthesizes two lactonases YtnP and Y2-aiiA, that have the different cellular localization, but also different substrate specificity, which could imply the difference in their biological roles. S. maltophilia 6960 YtnP lactonase has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic microscopy analysis showed a strong effect of analyzed lactonases on preventing biofilm formationand initiating the decomposition of the preformed biofilm of P. aeruginosa MMA83. Functional assays showed that lactonases have the ability to significantly reduce extracellular virulence factors production – elastase, pyocyanin and rhamnolipid. Additionally, the results obtained by real-time quantitative PCR showed that analyzed recombinant enzymes significantly downregulated all three analyzed P. aeruginosa QS networks at the transcriptional level. Finally, S. maltophilia 6960 YtnP lactonase significantly prolonged survival of Caenorhabditis elegans by reducing virulence of P. aeruginosa using fastkilling liquid assay. The described properties make B. cepacia and S. maltophilia lactonases the promising therapeutic candidates for the development of nextgeneration antivirulence agents.Book of abstracts and conference proceedings / 3rd International Conference Antimicrobial Resistance - Current State and Perspectives, 16-18. May 2024, Novi Sad, Serbia

A novel thermostable YtnP lactonase inhibits biofilm formation and induces decomposition of preformed Pseudomonas aeruginosa biofilms

Biofilm-associated infections are the main cause of biomaterial implant failure today. The increasing prevalence of antibiotic-resistant pathogens often results in the only solution of implant movement, with serious consequences for patients. Recently, various antimicrobial agents have been recognized as a promising strategy to prevent biofilm formation on implant surfaces. Quorum sensing (QS) plays a central role in the control of bacterial virulence and biofilm formation. The use of quorum quenching (QQ) enzymes to target QS is therefore a promising innovative approach for the development of enzyme-based antivirulence therapeutics, which represent a potential solution to combat infections caused by multidrug-resistant pathogens. This study aimed to characterize the novel YtnP lactonase from the clinical isolate Stenotrophomonas maltophilia 6960 and to investigate its potential to combat the virulence of multidrug-resistant (MDR) Pseudomonas aeruginosa MMA83

A decision support system for electrode shaping in multi-pad FES foot drop correction

Background: Functional electrical stimulation (FES) can be applied as an assistive and therapeutic aid in the rehabilitation of foot drop. Transcutaneous multi-pad electrodes can increase the selectivity of stimulation; however, shaping the stimulation electrode becomes increasingly complex with an increasing number of possible stimulation sites. We described and tested a novel decision support system (DSS) to facilitate the process of multi-pad stimulation electrode shaping. The DSS is part of a system for drop foot treatment that comprises a customdesigned multi-pad electrode, an electrical stimulator, and an inertial measurement unit. Methods: The system was tested in ten stroke survivors (3-96 months post stroke) with foot drop over 20 daily sessions. The DSS output suggested stimulation pads and parameters based on muscle twitch responses to short stimulus trains. The DSS ranked combinations of pads and current amplitudes based on a novel measurement of the quality of the induced movement and classified them based on the movement direction (dorsiflexion, plantar flexion, eversion and inversion) of the paretic foot. The efficacy of the DSS in providing satisfactory pad-current amplitude choices for shaping the stimulation electrode was evaluated by trained clinicians. The range of paretic foot motion was used as a quality indicator for the chosen patterns. Results: The results suggest that the DSS output was highly effective in creating optimized FES patterns. The position and number of pads included showed pronounced inter-patient and inter-session variability; however, zones for inducing dorsiflexion and plantar flexion within the multi-pad electrode were clearly separated. The range of motion achieved with FES was significantly greater than the corresponding active range of motion (p < 0.05) during the first three weeks of therapy. Conclusions: The proposed DSS in combination with a custom multi-pad electrode design covering the branches of peroneal and tibial nerves proved to be an effective tool for producing both the dorsiflexion and plantar flexion of a paretic foot. The results support the use of multi-pad electrode technology in combination with automatic electrode shaping algorithms for the rehabilitation of foot drop.The research has been supported in part by grants of the Basque Government (PI2013-10), the ERA-NET EU/MINECO project (INDIGO-DBT2-051) and by the Ministry of Education, Science and Technological Development of Serbia (Project no. 175016)

The Impact of Stimulation Intensity on Spatial Discrimination with Multi-Pad Finger Electrode

Multi-pad electrotactile stimulation can be used to provide tactile feedback in different applications. The electrotactile interface needs to be calibrated before each use, which entails adjusting the intensity to obtain clear sensations while allowing the subjects to differentiate between active pads. The present study investigated how the stimulation intensity affects the localization of sensations using a multi-pad electrode placed on a fingertip and proximal phalange. First, the sensation, localization, smearing and discomfort thresholds were determined in 11 subjects. Then, the same subjects performed a spatial discrimination test across a range of stimulation intensities. The results have shown that all thresholds were significantly different, while there was no difference in the threshold values between the pads and phalanges. Despite the subjective feeling of spreading of sensations, the success rates in spatial discrimination were not significantly different across the tested stimulation intensities. However, the performance was better for distal compared to proximal phalange. Presented results indicate that spatial discrimination is robust to changes in the stimulation intensity. Considering the lack of significant difference in the thresholds between the pads, these results imply that more coarse adjustment of stimulation amplitude (faster calibration) might be enough for practical applications of a multi-pad electrotactile interface.This research was funded by the TACTILITY project, which has received funding by European Union’s Horizon 2020 framework programme for research and innovation H2020-ICT 2018-2020/H2020-ICT-2018-3 under grant agreement no. 856718

A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo

Infections caused by multidrug-resistant pathogens are one of the biggest challenges facing the healthcare system today. Quorum quenching (QQ) enzymes have the potential to be used as innovative enzyme-based antivirulence therapeutics to combat infections caused by multidrug-resistant pathogens. The main objective of this research was to describe the novel YtnP lactonase derived from the clinical isolate Stenotrophomonas maltophilia and to investigate its antivirulence potential against multidrug-resistant Pseudomonas aeruginosa MMA83. YtnP lactonase, the QQ enzyme, belongs to the family of metallo-β-lactamases. The recombinant enzyme has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic effect. High-performance liquid chromatography analysis revealed the activity of recombinant YtnP lactonase toward a wide range of N-acyl-homoserine lactones (AHLs), quorum sensing signaling molecules, with a higher preference for long-chain AHLs. Recombinant YtnP lactonase was shown to inhibit P. aeruginosa MMA83 biofilm formation, induce biofilm decomposition, and reduce extracellular virulence factors production. Moreover, the lifespan of MMA83-infected Caenorhabditis elegans was prolonged with YtnP lactonase treatment. YtnP lactonase showed synergistic inhibitory activity in combination with gentamicin and acted additively with meropenem against MMA83. The described properties make YtnP lactonase a promising therapeutic candidate for the development of next-generation antivirulence agents

Electrotactile Communication via Matrix Electrode Placed on the Torso Using Fast Calibration, and Static vs. Dynamic Encoding

Electrotactile stimulation is a technology that reproducibly elicits tactile sensations and can be used as an alternative channel to communicate information to the user. The presented work is a part of an effort to develop this technology into an unobtrusive communication tool for first responders. In this study, the aim was to compare the success rate (SR) between discriminating stimulation at six spatial locations (static encoding) and recognizing six spatio-temporal patterns where pads are activated sequentially in a predetermined order (dynamic encoding). Additionally, a procedure for a fast amplitude calibration, that includes a semi-automated initialization and an optional manual adjustment, was employed and evaluated. Twenty subjects, including twelve first responders, participated in the study. The electrode comprising the 3 × 2 matrix of pads was placed on the lateral torso. The results showed that high SRs could be achieved for both types of message encoding after a short learning phase; however, the dynamic approach led to a statistically significant improvement in messages recognition (SR of 93.3%), compared to static stimulation (SR of 83.3%). The proposed calibration procedure was also effective since in 83.8% of the cases the subjects did not need to adjust the stimulation amplitude manually