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Abstract Background Symptoms reported by patients who sustain a concussion are non-specific. As such, clinicians are better able to manage patients when a standardized clinical exam is performed to sub-type the driver(s) of symptoms. Aerobic exercise and multimodal rehabilitation have consistently shown to be a possibly effective means to manage this population; however, the optimal training prescription is unclear. Thus, there is a need to further examine the effectiveness of personalized rehabilitative treatments. Our primary aim is to evaluate the response to personalized therapy on recovery, as measured by The Rivermead Post-concussion Symptoms Questionnaire (RPQ) when compared to an active control. Methods We will conduct a multi-center 12-week case-crossover randomized controlled trial. 50 participants will be recruited from out-patient University Health Network clinics and community-based clinical practices around the greater Toronto area. Participants will be randomized at baseline to Group A: a personalized care program followed by an active control or Group B: an active control followed by a personalized care program. Participants will be included should they be 21 years of age and older and have symptoms that have persisted beyond 4 weeks but less than 1 year. Participants will undergo 6-weeks of care in their respective streams. After 6-weeks, participants will undergo a re-examination. They will then crossover and undertake the alternative treatment for 6 weeks. At the end of 12 weeks, participants will undertake the endpoint examinations. The primary outcome will be the Rivermead Postconcussion Questionnaire (RPQ). The secondary outcomes will be changes in standardized clinical examination, Neck Disability Index (NDI), Patient Health Questionnaire (PHQ-9) and an electroencephalography (EEG) via NeuroCatch™. The statistical analysis to be performed is composed of an adjusted model using an analysis of variance, specifically using an unpaired t-test to test for associations between variables and outcomes. Discussion Given the recommendations from reviews on the topic of rehabilitation for adults with persistent concussion symptoms, we are undertaking a controlled trial. The documented high costs for patients seeking care for persistent symptoms necessitate the need to evaluate the effectiveness of a personalized rehabilitative program compared to the current standard of care. Trial registration ClinicalTrials.gov ID: NCT06069700.

Abstract Background Functional electrical stimulation (FES) is a rehabilitation technique that enables functional improvements in patients with motor control impairments. This study presents an original design and prototyping method for a smart sleeve for FES applications. The article explains how to integrate a carbon-based dry electrode into a textile structure and ensure an electrical connection between the electrodes and the stimulator for effective delivery of the FES. It also describes the materials and the step-by-step manufacturing processes. Results The carbon-based dry electrode is integrated into the textile substrate by a thermal compression molding process on an embroidered conductive matrix. This matrix is composed of textile silver-plated conductive yarns and is linked to the stimulator. Besides ensuring the electrical connection, the matrix improves the fixation between the textile substrate and the electrode. The stimulation intensity, the perceived comfort and the muscle torque generated by the smart FES sleeve were compared to hydrogel electrodes. The results show a better average comfort and a higher average stimulation intensity with the smart FES sleeve, while there were no significant differences for the muscle torque generated. Conclusions The integration of the proposed dry electrodes into a textile is a viable solution. The wearable FES system does not negatively impact the electrodes’ performance, and tends to improve it. Additionally, the proposed prototyping method is applicable to an entire garment in order to target all muscles. Moreover, the process is feasible for industrial production and commercialization since all materials and processes used are already available on the market.

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson’s disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.

Abstract Background Functional electrical stimulation (FES) can be used in rehabilitation to aid or improve function in people with paralysis. In clinical settings, it is common practice to use transcutaneous electrodes to apply the electrical stimulation, since they are non-invasive, and can be easily applied and repositioned as necessary. However, the current electrode options available for transcutaneous FES are limited and can have practical disadvantages, such as the need for a wet interface with the skin for better comfort and performance. Hence, we were motivated to develop a dry stimulation electrode which could perform equivalently or better than existing commercially available options. Methods We manufactured a thin-film dry polymer nanocomposite electrode, characterized it, and tested its performance for stimulation purposes with thirteen healthy individuals. We compared its functionality in terms of stimulation-induced muscle torque and comfort level against two other types of transcutaneous electrodes: self-adhesive hydrogel and carbon rubber. Each electrode type was also tested using three different stimulators and different intensity levels of stimulation. Results We found the proposed dry polymer nanocomposite electrode to be functional for stimulation, as there was no statistically significant difference between its performance to the other standard electrodes. Namely, the proposed dry electrode had comparable muscle torque generated and comfort level as the self-adhesive hydrogel and carbon rubber electrodes. From all combinations of electrode type and stimulators tested, the dry polymer nanocomposite electrode with the MyndSearch stimulator had the most comfortable average rating. Conclusions The dry polymer nanocomposite electrode is a durable and flexible alternative to existing self-adhesive hydrogel and carbon rubber electrodes, which can be used without the addition of a wet interfacing agent (i.e., water or gel) to perform as well as the current electrodes used for stimulation purposes.

Abstract Background The escalating impact of diabetes and its complications, including diabetic foot ulcers (DFUs), presents global challenges in quality of life, economics, and resources, affecting around half a billion people. DFU healing is hindered by hyperglycemia-related issues and diverse diabetes-related physiological changes, necessitating ongoing personalized care. Artificial intelligence and clinical research strive to address these challenges by facilitating early detection and efficient treatments despite resource constraints. This study establishes a standardized framework for DFU data collection, introducing a dedicated case report form, a comprehensive dataset named Zivot with patient population clinical feature breakdowns and a baseline for DFU detection using this dataset and a UNet architecture. Results Following this protocol, we created the Zivot dataset consisting of 269 patients with active DFUs, and about 3700 RGB images and corresponding thermal and depth maps for the DFUs. The effectiveness of collecting a consistent and clean dataset was demonstrated using a bounding box prediction deep learning network that was constructed with EfficientNet as the feature extractor and UNet architecture. The network was trained on the Zivot dataset, and the evaluation metrics showed promising values of 0.79 and 0.86 for F1-score and mAP segmentation metrics. Conclusions This work and the Zivot database offer a foundation for further exploration of holistic and multimodal approaches to DFU research.

Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson’s disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists’ expertise and patients’ experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients’ symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity.Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim–DBS are linked to symptomatic changes in EMG signals. By using a proportional–integral–derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim–DBS so that the power of EMG reaches a desired control target.Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.

The development of appropriate and valid multicultural and multilingual instruments research is necessary due to a growing multicultural and multilingual society in the 21st century. We explored the use of a cognitive scale related to subjective complaints, focusing on the first step: a cross-cultural and semantic validation. This study presents the translation and cross-validation process of the “Subjective Scale to Investigate Cognition in Schizophrenia” (SSTICS) for the United Arab Emirates (UAE) region via different languages used in Dubaï/Abu Dhabi. This scale measures cognitive complaints and has been validated with psychosis and used in 20 clinical trials worldwide. It evaluates areas of the illness related to self-awareness focusing on memory dysfunction and deficits of attention, language, and praxis. We described the method of cross-cultural validation, with back-translation, semantic steps, and societal contexts. The use of the Subjective Scale to Investigate Cognition in Emirates (SSTIC-E) was explored with different samples of UAE Arabic-speaking subjects. First, a pilot sample mean SSTICS total score was 16.5 (SD:16.9); (p

Abstract Background There is growing public policy and research interest in the development and use of various technologies for managing violence in healthcare settings to protect the health and well-being of patients and workers. However, little research exists on the impact of technologies on violence prevention, and in particular in the context of rehabilitation settings. Our study addresses this gap by exploring the perceptions and experiences of rehabilitation professionals regarding how technologies are used (or not) for violence prevention, and their perceptions regarding their efficacy and impact. Methods This was a descriptive qualitative study with 10 diverse professionals (e.g., physical therapy, occupational therapy, recreation therapy, nursing) who worked across inpatient and outpatient settings in one rehabilitation hospital. Data collection consisted of semi-structured interviews with all participants. A conventional approach to content analysis was used to identify key themes. Results We found that participants used three types of technologies for violence prevention: an electronic patient flagging system, fixed and portable emergency alarms, and cameras. All of these were perceived by participants as being largely ineffective for violence prevention due to poor design features, malfunction, limited resources, and incompatibility with the culture of care. Our analysis further suggests that professionals’ perception that these technologies would not prevent violence may be linked to their focus on individual patients, with a corresponding lack of attention to structural factors, including the culture of care and the organizational and physical environment. Conclusions Our findings suggest an urgent need for greater consideration of structural factors in efforts to develop effective interventions for violence prevention in rehabilitation settings, including the design and implementation of new technologies.

Abstract Background Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new “mind-body” intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD. Methods A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD. Results A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury may enhance central neuroplasticity, restoring lost sensorimotor function. These neuroplastic effects suggest that FES may be a promising innovative intervention for psychiatric disorders of disrupted brain connectivity, such as MDD. Recent pilot data on repetitive FES applied to the facial muscles in healthy participants and patients with MDD show early promise, suggesting that FES may attenuate the negative interoceptive bias associated with MDD by enhancing positive facial feedback. Neurobiologically, the amygdala and nodes of the emotion-to-motor transformation loop may serve as potential neural targets for facial FES in MDD, as they integrate proprioceptive and interoceptive inputs from muscles of facial expression and fine-tune their motor output in line with socio-emotional context. Conclusions Manipulating facial muscles may represent a mechanistically novel treatment strategy for MDD and other disorders of disrupted brain connectivity that is worthy of investigation in phase II/III trials.

Nitric oxide (NO•) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO• also occurs in vivo. Here we investigated the production of NO• from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO• from nitrite and ascorbate that slows with increasing pH. The formation of NO• was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO• was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO•-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO• is not likely to be significant process in vivo in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, e.g. stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate.

Functional electrical stimulation (FES) has been a useful therapeutic tool in rehabilitation, particularly for people with paralysis. To deliver stimulation in its most basic setup, a stimulator and at least a pair of electrodes are needed. The electrodes are an essential part of the system since they allow the transduction of the stimulator signals into the body. Their performance can influence the experience of both patient and therapist in terms of movement generation, comfort, and ease of use. For non-invasive surface stimulation, current electrode options have several limitations involving their interfacing with the skin, practical inconveniences, and short-term functionality. Standard hydrogel electrodes tend to lose their adhesion with the skin quickly, while dry or textile electrodes require constant wetting to be comfortable. In this paper, we present the fabrication, characterization, and FES testing of a new aerogel-based wet electrode for surface stimulation applications for long-term and reusable FES applications. We investigated its functionality by stimulating the biceps brachii of twelve healthy individuals and collected elbow joint torque and comfort ratings for three different intensity levels (low, moderate, and high) of FES. Comparing to standard hydrogel electrodes, no statistically significant difference was found for any intensity of stimulation in either torque or comfort. Overall, the new aerogel-based electrode has an appropriate impedance, is flexible and soft, is conformable to the skin, has a high water absorption and retention, and can be used for FES purposes.

The authors report how the cold and heat sensing properties of the pain receptor TRPA1 are separately modulated by the C-terminal intracellular domain, and in concert with either the S1–S4 or the S5–S6 transmembrane domain.

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD). Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .013). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation but not in SNr (p