A high-performance 8 nV/root Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals

Background: It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals. Methods: To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. Results: To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented. Conclusions: The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments

Objective assessment of bradykinesia in Parkinson’s disease using evolutionary algorithms: clinical validation

Background: There is an urgent need for developing objective, effective and convenient measurements to help clinicians accurately identify bradykinesia. The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping (FT) that uses evolutionary algorithms (EAs) and explore whether it can be used to identify early stage Parkinson’s disease (PD). Methods: One hundred and seven PD, 41 essential tremor (ET) patients and 49 normal controls (NC) were recruited. Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger. Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs. The output from the device (referred to as "PD-Monitor") scaled from − 1 to +1 (where higher scores indicate greater severity of bradykinesia). Meanwhile, the bradykinesia was rated clinically using the Movement Disorder Society- Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) FT item. Results: With an increasing MDS-UPDRS FT score, the PD-Monitor score from the same hand side increased correspondingly. PD-Monitor score correlated well with MDS-UPDRS FT score (right side: r = 0.819, P = 0.000; left side: r = 0.783, P = 0.000). Moreover, PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup (FT bradykinesia scored from 1 to 3) were all higher than that in NC. Receiver operating characteristic (ROC) curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy (≥89.7%) in the right dominant hand. Furthermore, PD-Monitor scores could discriminate early stage PD from NC, with area under the ROC curve greater than or equal to 0.899. Additionally, ET without bradykinesia could be differentiated from PD by PD-Monitor scores. A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides. Conclusions: Our study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD, but also had the potential to differentiate early stage PD from normality

Enhanced Effect of Combining Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and to Restore Cardiac Function After Myocardial Infarction

BACKGROUND: As mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h)MSCs with c-kit+ hCSCs produces greater infarct size reduction compared to either cell administered alone after MI. METHODS AND RESULTS: Yorkshire swine underwent balloon occlusion of the LAD coronary artery followed by reperfusion, and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial injection of either: combination hCSCs/hMSCs (1M/200M, n=5), hCSCs alone (1M, n=5), hMSCs alone (200M, n=5), or placebo (PBS, n=5) was administered to the infarct border zones at 14 days post-MI. Phenotypic response to cell therapy was assessed by cardiac MRI and micromanometer conductance catheterization hemodynamics. While each cell therapy group had reduced MI size relative to placebo (p<0.05), the MI size reduction was 2-fold greater in combination vs. either cell therapy alone (p<0.05). Accompanying enhanced MI size reduction was substantial improvement in LV chamber compliance (end-diastolic pressure volume relationship, p<0.01) and contractility (preload recruitable stroke work and dP/dt(max), p<0.05) in combination treated swine. EF was restored to baseline in cell treated pigs, while placebo pigs had persistently depressed LV function (p<0.05). Immunohistochemistry showed 7-fold enhanced engraftment of stem cells in the combination therapy group vs. either cell type alone (P<0.001). CONCLUSIONS: Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction, and restores diastolic and systolic function toward normal after MI. Taken together these findings illustrate important biological interactions between c-kit+ CSCs and MSCs that enhance cell-based therapeutic responses