A Tangible Solution for Hand Motion Tracking in Clinical Applications

Objective real-time assessment of hand motion is crucial in many clinical applications including technically-assisted physical rehabilitation of the upper extremity. We propose an inertial-sensor-based hand motion tracking system and a set of dual-quaternion-based methods for estimation of finger segment orientations and fingertip positions. The proposed system addresses the specific requirements of clinical applications in two ways: (1) In contrast to glove-based approaches, the proposed solution maintains the sense of touch. (2) In contrast to previous work, the proposed methods avoid the use of complex calibration procedures, which means that they are suitable for patients with severe motor impairment of the hand. To overcome the limited significance of validation in lab environments with homogeneous magnetic fields, we validate the proposed system using functional hand motions in the presence of severe magnetic disturbances as they appear in realistic clinical settings. We show that standard sensor fusion methods that rely on magnetometer readings may perform well in perfect laboratory environments but can lead to more than 15 cm root-mean-square error for the fingertip distances in realistic environments, while our advanced method yields root-mean-square errors below 2 cm for all performed motions.DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders.

ABC transporters use the energy from binding and hydrolysis of ATP to import or extrude substrates across the membrane. Using ribosome display, we raised designed ankyrin repeat proteins (DARPins) against detergent solubilized LmrCD, a heterodimeric multidrug ABC exporter from Lactococcus lactis. Several target-specific DARPin binders were identified that bind to at least three distinct, partially overlapping epitopes on LmrD in detergent solution as well as in native membranes. Remarkably, functional screening of the LmrCD-specific DARPin pools in L. lactis revealed three homologous DARPins which, when generated in LmrCD-expressing cells, strongly activated LmrCD-mediated drug transport. As LmrCD expression in the cell membrane was unaltered upon the co-expression of activator DARPins, the activation is suggested to occur at the level of LmrCD activity. Consistent with this, purified activator DARPins were found to stimulate the ATPase activity of LmrCD in vitro when reconstituted in proteoliposomes. This study suggests that membrane transporters are tunable in vivo by in vitro selected binding proteins. Our approach could be of biopharmaceutical importance and might facilitate studies on molecular mechanisms of ABC transporters

Why does the gout attack stop? A roadmap for the immune pathogenesis of gout

Gout is one of the most severe and frequent rheumatic diseases. Clinical manifestations of gout arise from uric acid crystal deposition in the musculoskeletal tissue. At high concentrations of uric acid in the body (hyperuricaemia), needle-shaped monosodium urate (MSU) crystals are formed. The structures are ingested by neutrophils and monocytes and thereby trigger robust activation of the inflammasome, an intracellular protein complex mounting an inflammatory response. Inflammasome activation builds interleukin-1, which acts as a proinflammatory mediator and induces vasodilation, recruitment of additional leucocytes and the expression of proinflammatory cytokines and chemokines. This process is associated with the clinical manifestation of an acute gout attack. Such attacks, however, stop rather rapidly and the process of resolution of inflammation in gout is now better defined. Neutrophils having ingested MSU crystals undergo a specific form of cell death called NETosis, which is characterised by the formation of neutrophil extracellular traps (NETs). During this process, DNA is extruded, allowing the dense packaging of MSU crystals as well as the degradation of proinflammatory cytokines, thereby allowing the stopping of the inflammatory process. Reactive oxygen species are essential for forming NETs and for allowing the resolution of inflammation in gout. This process of NETosis is critical for understanding tophaceous gout, since tophi are composed of NETs and densely packed MSU crystals

A new semi-automatic approach to find suitable virtual electrodes in arrays using an interpolation strategy

Functional Electrical Stimulation via electrode arrays enables the user to form virtual electrodes (VEs) of dynamic shape, size, and position. We developed a feedback-control-assisted manual search strategy which allows the therapist to conveniently and continuously modify VEs to find a good stimulation area. This works for applications in which the desired movement consists of at least two degrees of freedom. The virtual electrode can be moved to arbitrary locations within the array, and each involved element is stimulated with an individual intensity. Meanwhile, the applied global stimulation intensity is controlled automatically to meet a predefined angle for one degree of freedom. This enables the therapist to concentrate on the remaining degree(s) of freedom while changing the VE position. This feedback-control-assisted approach aims to integrate the user's opinion and the patient's sensation. Therefore, our method bridges the gap between manual search and fully automatic identification procedures for array electrodes. Measurements in four healthy volunteers were performed to demonstrate the usefulness of our concept, using a 24-element array to generate wrist and hand extension.BMBF, 16SV7069K, Verbundprojekt: Bewegungsfähigkeit und Mobilität wiedererlangen - BeMobil -; Teilvorhaben: Nutzerzentrierte Entwicklung technischer Methoden für eine optimale Mensch-Technik-Interaktion in der Bewegungsrehabilitatio

Intention recognition for FES in a grasp-and-release task using volitional EMG and inertial sensors

Functional Electrical Stimulation (FES) facilitates the motor recovery of the hand function after stroke. The integration of biofeedback and other strategies to actively involve a patient in the therapy is important for the rehabilitation progress. We introduce a combined control approach for a FES-driven neuroprosthesis using volitional electromyo-graphy (vEMG) and motion capturing via a novel inertial sensor network for patients that still possess a residual activity in the paralyzed muscles. A real-time vEMG measurement and signal processing in between stimulation pulses has been realized during active FES. Experiments showed that our system allows for quick adaption to individual users.BMBF, 16SV7069K, Verbundprojekt: Bewegungsfähigkeit und Mobilität wiedererlangen - BeMobil -; Teilvorhaben: Nutzerzentrierte Entwicklung technischer Methoden für eine optimale Mensch-Technik-Interaktion in der Bewegungsrehabilitatio

Modular finger and hand motion capturing system based on inertial and magnetic sensors

The assessment of hand posture and kinematicsis increasingly important in various fields. This includesthe rehabilitation of stroke survivors with restricted handfunction. This paper presents a modular, ambulatory mea-surement system for the assement of the remaining handfunction and for closed-loop controlled therapy. The de-vice is based on inertial sensors and utilizes up to fiveinterchangeable sensor strips to achieve modularity and tosimplify the sensor attachment. We introduce the modularhardware design and describe algorithms used to calculatethe joint angles. Measurements with two experimentalsetups demonstrate the feasibility and the potential of such a tracking device.BMBF, 16SV7069K, Verbundprojekt: Bewegungsfähigkeit und Mobilität wiedererlangen - BeMobil -; Teilvorhaben: Nutzerzentrierte Entwicklung technischer Methoden für eine optimale Mensch-Technik-Interaktion in der Bewegungsrehabilitatio

Do neurooncological patients and their significant others agree on quality of life ratings?

<p>Abstract</p> <p>Introduction</p> <p>Patients suffering from brain tumours often experience a wide range of cognitive impairments that impair their ability to report on their quality of life and symptom burden. The use of proxy ratings by significant others may be a promising alternative to gain information for medical decision making or research purposes, if self-ratings are not obtainable. Our study investigated the agreement of quality of life and symptom ratings by the patient him/herself or by a significant other.</p> <p>Methods</p> <p>Patients with primary brain tumours were recruited at the neurooncological outpatient unit of Innsbruck Medical University. Quality of life self- and proxy-ratings were collected using the EORTC QLQ-C30 and its brain cancer module, the QLQ-BN20.</p> <p>Results</p> <p>Between May 2005 and August 2007, 42 pairs consisting of a patient and his/her significant other were included in the study. Most of the employed quality of life scales showed fairly good agreement between patient- and proxy-ratings (median correlation 0.46). This was especially true for Physical Functioning, Sleeping Disturbances, Appetite Loss, Constipation, Taste Alterations, Visual Disorders, Motor Dysfunction, Communication Deficits, Hair Loss, Itchy Skin, Motor Dysfunction and Hair Loss. Worse rater agreement was found for Social Functioning, Emotional Functioning, Cognitive Functioning, Fatigue, Pain, Dyspnoea and Seizures.</p> <p>Conclusion</p> <p>The assessment of quality of life in brain cancer patients through ratings from their significant others seems to be a feasible strategy to gain information about certain aspects of patient's quality of life and symptom burden, if the patient is not able to provide information himself.</p

Hypoxia Promotes Neutrophil Survival After Acute Myocardial Infarction

Phagocytosis, degranulation, and neutrophil extracellular traps (NETs) formation build the armory of neutrophils for the first line of defense against invading pathogens. All these processes are modulated by the microenvironment including tonicity, pH and oxygen levels. Here we investigated the neutrophil infiltration in cardiac tissue autopsy samples of patients with acute myocardial infarction (AMI) and compared these with tissues from patients with sepsis, endocarditis, dermal inflammation, abscesses and diseases with prominent neutrophil infiltration. We observed many neutrophils infiltrating the heart muscle after myocardial infarction. Most of these had viable morphology and only few showed signs of nuclear de-condensation, a hallmark of early NET formation. The abundance of NETs was the lowest in acute myocardial infarction when compared to other examined diseases. Since cardiac oxygen supply is abruptly abrogated in acute myocardial infarction, we hypothesized that the resulting tissue hypoxia increased the longevity of the neutrophils. Indeed, the viable cells showed increased nuclear hypoxia inducible factor-1α (HIF-1α) content, and only neutrophils with low HIF-1α started the process of NET formation (chromatin de-condensation and nuclear swelling). Prolonged neutrophil survival, increased oxidative burst and reduced NETs formation were reproduced under low oxygen tensions and by HIF-1α stabilization in vitro. We conclude that nuclear HIF-1α is associated with prolonged neutrophil survival and enhanced oxidative stress in hypoxic areas of AMI

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/-mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals\u27 lifespans. METHODS. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety. RESULTS. At 12 weeks, statistically significant median (IQR) reductions in the Epidermolysis Bullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0% (2.9%-30%; P = 0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB-c) score of 18.2% (1.9%-39.8%; P = 0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%-42.9%; P = 0.033) and 25.0% (-8.4% to 46.4%; P = 0.168), respectively. Three adverse events were considered related to the cell product: 1 mild lymphadenopathy and 2 hypersensitivity reactions. The latter 2 were serious but resolved without sequelae shortly after withdrawal of treatment. CONCLUSION. This trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5+ MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation