Characterization of Magnetoresistive Shunts and Its Sensitivity Temperature Compensation.

The main purpose of the paper is to show how a magnetoresistive (MR) element can work as a current sensor instead of using a Wheatstone bridge composed by four MR elements, defining the concept of a magnetoresistive shunt (MR-shunt). This concept is reached by considering that once the MR element is biased at a constant current, the voltage drop between its terminals offers information, by the MR effect, of the current to be measured, as happens in a conventional shunt resistor. However, an MR-shunt has the advantage of being a non-dissipative shunt since the current of interest does not circulate through the material, preventing its self-heating. Moreover, it provides galvanic isolation. First, we propose an electronic circuitry enabling the utilization of the available MR sensors integrated into a Wheatstone bridge as sensing elements (MR-shunt). This circuitry allows independent characterization of each of the four elements of the bridge. An independently implemented MR element is also analyzed. Secondly, we propose an electronic conditioning circuit for the MR-shunt, which allows both the bridge-integrated element and the single element to function as current sensors in a similar way to the sensing bridge. Third, the thermal variation in the sensitivity of the MR-shunt, and its temperature coefficient, are obtained. An electronic interface is proposed and analyzed for thermal drift compensation of the MR-shunt current sensitivity. With this hardware compensation, temperature coefficients are experimentally reduced from 0.348%/°C without compensation to -0.008%/°C with compensation for an element integrated in a sensor bridge and from 0.474%/°C to -0.0007%/°C for the single element.

A magnetic nanoparticle-based microfluidic device fabricated using a 3D-printed mould for separation of Escherichia coli from blood.

Herein, A microfluidic device is described, produced with a 3D-printed master mould that rapidly separates and concentrates Escherichia coli directly from whole blood samples, enabling a reduction in the turnaround time of bloodstream infections (BSIs) diagnosis. Moreover, it promotes the cleansing of the blood samples whose complexity frequently hampers bacterial detection. The device comprises a serpentine mixing channel with two inlets, one for blood samples (spiked with bacteria) and the other for magnetic nanoparticles (MNPs) functionalized with a (bacterio)phage receptor-binding protein (RBP) with high specificity for E. coli. After the magnetic labelling of bacteria throughout the serpentine, the microchannel ends with a trapping reservoir where bacteria-MNPs conjugates are concentrated using a permanent magnet. The optimized sample preparation device successfully recovered E. coli (on average, 66%) from tenfold diluted blood spiked within a wide range of bacterial load (102 CFU to 107 CFU mL-1). The non-specific trapping, tested with Staphylococcus aureus, was at a negligible level of 12%. The assay was performed in 30 min directly from diluted blood thus presenting an advantage over the conventional enrichment in blood cultures (BCs). The device is simple and cheap to fabricate and can be tailored for multiple bacterial separation from complex clinical samples by using RBPs targeting different species. Moreover, the possibility to integrate a biosensing element to detect bacteria on-site can provide a reliable, fast, and cost-effective point-of-care device.

Dependence of Sensitivity, Derivative of Transfer Curve and Current on Bias Voltage Magnitude and Polarity in Tunneling Magnetoresistance Sensors.

The sensitivity of tunneling magnetoresistance sensors is an important performance parameter. It depends on the derivative of resistance versus magnetic field (transfer curve) and the current and is expressed as the product of the two factors. Previous research has demonstrated that the bias voltage has a significant impact on the sensitivity. However, no research has been conducted into the dependence of current and the derivative on bias voltage magnitude and polarity, and their contribution to the sensitivity. Thus, this paper investigates the dependence of sensitivity, derivative of resistance versus magnetic field curve and current on bias voltage magnitude and polarity in CoFeB/MgO/CoFeB-based tunneling magnetoresistance sensors with weak, strong and no voltage-controlled perpendicular magnetic anisotropy modification. It demonstrates that the sensitivity dependence on bias voltage for sensors with voltage controlled magnetic anisotropy modification showed no saturation up to 1 V. Moreover, the sensitivity asymmetry with respect to bias polarity changed significantly with bias, reaching a ratio of 6.7. Importantly, the contribution of current and the derivative of resistance versus magnetic field curve to the sensitivity showed a crossover. The current dominated the bias dependence of sensitivity below the crossover voltage and the derivative above the voltage. Furthermore, the crossover voltage in sensors without voltage controlled magnetic anisotropy modification did not depend on polarity, whereas in sensors with voltage controlled magnetic anisotropy modification, it appeared at significantly higher voltage under positive than negative polarity.

A Lab-on-a-Chip Approach for the Detection of the Quarantine Potato Cyst Nematode Globodera pallida.

The potato cyst nematode (PCN), Globodera pallida, has acquired significant importance throughout Europe due to its widespread prevalence and negative effects on potato production. Thus, rapid and reliable diagnosis of PCN is critical during surveillance programs and for the implementation of control measures. The development of innovative technologies to overcome the limitations of current methodologies in achieving early detection is needed. Lab-on-a-chip devices can swiftly and accurately detect the presence of certain nucleotide sequences with high sensitivity and convert the presence of biological components into an understandable electrical signal by combining biosensors with microfluidics-based biochemical analysis. In this study, a specific DNA-probe sequence and PCR primers were designed to be used in a magnetoresistive biosensing platform to amplify the internal transcribed spacer region of the ribosomal DNA of G. pallida. Magnetic nanoparticles were used as the labelling agents of asymmetric PCR product through biotin−streptavidin interaction. Upon target hybridization to sensor immobilized oligo probes, the fringe field created by the magnetic nanoparticles produces a variation in the sensor's electrical resistance. The detection signal corresponds to the concentration of target molecules present in the sample. The results demonstrate the suitability of the magnetic biosensor to detect PCR target product and the specificity of the probe, which consistently distinguishes G. pallida (DV/V > 1%) from other cyst nematodes (DV/V < 1%), even when DNA mixtures were tested at different concentrations. This shows the magnetic biosensor's potential as a bioanalytical device for field applications and border phytosanitary inspections.

A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers.

This research proposes a low-cost and simple operation microfluidic chip to enhance the magnetic labeling efficiency of two ischemic stroke biomarkers: cellular fibronectin (c-Fn) and matrix metallopeptidase 9 (MMP9). This fully portable and pump-free microfluidic chip is operated based on capillary attractions without any external power source and battery. It uses an integrated cellulose sponge to absorb the samples. At the same time, a magnetic field is aligned to hold the target labeled by the magnetic nanoparticles (MNPs) in the pre-concentrated chamber. By using this approach, the specific targets are labeled from the beginning of the sampling process without preliminary sample purification. The proposed study enhanced the labeling efficiency from 1 h to 15 min. The dynamic interactions occur in the serpentine channel, while the crescent formation of MNPs in the pre-concentrated chamber, acting as a magnetic filter, improves the biomarker-MNP interaction. The labeling optimization by the proposed device influences the dynamic range by optimizing the MNP ratio to fit the linear range across the clinical cutoff value. The limits of detection (LODs) of 2.8 ng/mL and 54.6 ng/mL of c-Fn measurement were achieved for undiluted and four times dilutions of MNP, respectively. While for MMP9, the LODs were 11.5 ng/mL for undiluted functionalized MNP and 132 ng/mL for four times dilutions of functionalized MNP. The results highlight the potential use of this device for clinical sample preparation and specific magnetic target labeling. When combined with a detection system, it could also be used as an integrated component of a point-of-care platform.

An integrated device for fast and sensitive immunosuppressant detection.

The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported.

Evolution in Automatized Detection of Cells: Advances in Magnetic Microcytometers for Cancer Cells.

Flow cytometers are well-established tools with fundamental importance in biology and medicine to examine and identify cell populations, density, size distributions, compositions, and disease diagnosis and monitoring. Still, these devices are expensive with a low level of integration for sample preparation. Miniaturized microfluidic cytometers, i.e., microcytometers, for monitoring cells in a wide range of biological samples are currently being developed, providing more affordable and integrated solutions. Several detection methods have been developed and applied in microcytometers such as electrical, optical, and magnetic sensing techniques, which are integrated with microfluidic technology. Magnetic microcytometers present several advantages when compared to optical systems such as the fact that these devices provide more stable labeling by using magnetic nanoparticles (MNPs) or beads (MBs) instead of fluorophores. In this chapter, we explore the evolution of the automation of whole cell detection and enumeration that led to the development of microcytometers and particularly examine the anatomy of magnetic microcytometers applied to cancer research. We then give an overview of the challenges of Circulating Tumor Cells enrichment and enumeration, and the progress of magnetic microcytometers in this field.

Immunocytochemical assessment of cell differentiation of podoplanin-positive osteoblasts into osteocytes in murine bone.

In this study, we examined the immunolocalization of podoplanin/E11, CD44, actin filaments, and phosphorylated ezrin in the osteoblasts on the verge of differentiating into osteocytes in murine femora and tibiae. When observing under stimulated emission depletion microscopy, unlike podoplanin-negative osteoblasts, podoplanin-positive osteoblasts showed a rearranged assembly of actin filaments along the cell membranes which resembled that of embedded osteocytes. In the metaphysis, i.e., the bone remodeling site, CD44-bearing osteoclasts were either proximal to or in contact with podoplanin-positive osteoblasts, but the podoplanin-positive osteoblasts also localized CD44 on their own cell surface. These podoplanin-positive osteoblasts, which either possessed CD44 on their cell surface or were close to CD44-bearing osteoclasts, showed phosphorylated ezrin-positivity on the cell membranes. Therefore, the CD44/podoplanin interaction on the cell surface may be involved in the osteoblastic differentiation into osteocytes in the metaphyses, via the mediation of podoplanin-driven ezrin phosphorylation and the subsequent reorganized assembly of actin filaments. Consistently, the protein expression of phosphorylated ezrin was increased after CD44 administration in calvarial culture. Conversely, in modeling sites such as the cortical bones, podoplanin-positive osteoblasts were uniformly localized at certain intervals even without contact with CD44-positive bone marrow cells; furthermore, they also exhibited phosphorylated ezrin immunoreactivity along their cell membranes. Taken together, it seems likely that the CD44/podoplanin interaction is involved in osteoblastic differentiation into osteocytes in the bone remodeling area but not in modeling sites.

Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones.

To verify whether PTH acts on bone-specific blood vessels and on cells surrounding these blood vessels, 6-week-old male mice were subjected to vehicle (control group) or hPTH [1-34] (20 µg/kg/day, PTH group) injections for 2 weeks. Femoral metaphyses were used for histochemical and immunohistochemical studies. In control metaphyses, endomucin-positive blood vessels were abundant, but αSMA-reactive blood vessels were scarce. In the PTH-administered mice, the lumen of endomucin-positive blood vessels was markedly enlarged. Moreover, many αSMA-positive cells were evident near the blood vessels, and seemed to derive from those vessels. These αSMA-positive cells neighboring the blood vessels showed features of mesenchymal stromal cells, such as immunopositivity for c-kit and tissue nonspecific alkaline phosphatase (TNALP). Thus, PTH administration increased the population of perivascular/stromal cells positive for αSMA and c-kit, which were likely committed to the osteoblastic lineage. To understand the cellular events that led to increased numbers and size of bone-specific blood vessels, we performed immunohistochemical studies for PTH/PTHrP receptor and VEGF. After PTH administration, PTH/PTHrP receptor, VEGF and its receptor flk-1 were consistently identified in both osteoblasts and blood vessels (endothelial cells and surrounding perivascular cells). Our findings suggest that exogenous PTH increases the number and size of bone-specific blood vessels while fostering perivascular/stromal cells positive for αSMA/TNALP/c-kit.

Further Insights into the Oxidative Pathway of Thiocarbonyl-Type Antitubercular Prodrugs: Ethionamide, Thioacetazone, and Isoxyl.

A chemical activation study of the thiocarbonyl-type antitubercular prodrugs, ethionamide (ETH), thioacetazone (TAZ), and isoxyl (ISO), was performed. Biomimetic oxidation of ethionamide using H2O2 (1 equiv) led to ETH-SO as the only stable S-oxide compound, which was found to occur in solution in the preferential form of a sulfine (ETH═S═O vs the sulfenic acid tautomer ETH-S-OH), as previously observed in the crystal state. It was also demonstrated that ETH-SO is capable of reacting with amines, as the putative sulfinic derivative (ETH-SO2H) was supposed to do. Unlike ETH, oxidation of TAZ did not allow observation of the mono-oxygenated species (TAZ-SO), leading directly to the more stable sulfinic acid derivative (TAZ-SO2H), which can then lose a SOxH group after further oxidation or when placed in a basic medium. It was also noticed that the unstable TAZ-SO intermediate can lead to the carbodiimide derivative as another electrophilic species. It is suggested that TAZ-SOH, TAZ-SO2H, and the carbodiimide compound can also react with NH2-containing nucleophilic species, and therefore be involved in toxic effects. Finally, ISO showed a very complex reactivity, here assigned to the coexistence of two mono-oxygenated structures, the sulfine and sulfenic acid tautomers. The mono- and dioxygenated derivatives of ISO are also highly unstable, leading to a panel of multiple metabolites, which are still reactive and likely contribute to the toxicity of this prodrug.

Rapid and multiplex detection of nosocomial pathogens on a phage-based magnetoresistive lab-on-chip platform.

Nosocomial or hospital-acquired infections (HAIs) have a major impact on mortality worldwide. Enterococcus and Staphylococcus are among the leading causes of HAIs and thus are important pathogens to control mainly due to their increased antibiotic resistance. The gold-standard diagnostic methods for HAIs are time-consuming, which hinders timely and adequate treatment. Therefore, the development of fast and accurate diagnostic tools is an urgent demand. In this study, we combined the sensitivity of magnetoresistive (MR) sensors, the portability of a lab-on-chip platform, and the specificity of phage receptor binding proteins (RBPs) as probes for the rapid and multiplex detection of Enterococcus and Staphylococcus. For this, bacterial cells were firstly labelled with magnetic nanoparticles (MNPs) functionalized with RBPs and then measured on the MR sensors. The results indicate that the RBP-MNPS provided a specific individual and simultaneous capture of more than 70% of Enterococcus and Staphylococcus cells. Moreover, high signals from the MR sensors were obtained for these samples, providing the detection of both pathogens at low concentrations (10 CFU/ml) in less than 2 h. Overall, the lab-on-chip MR platform herein presented holds great potential to be used as a point-of-care for the rapid, sensitive and specific multiplex diagnosis of bacterial infections.

Gait Parameters of Older Adults according to Their Fall History and Functional Capacity While Walking at Different Speeds.

INTRODUCTION: It is believed that functional capacity and fall history are factors capable of influencing the gait parameters of older adults. Thus, the objective of this study was to verify whether gait parameters of community-dwelling older adults differ according to their functional capacity and fall history when walking at self-selected walking speed (SSWS) and fast walking speed (FWS) using principal component analysis (PCA). METHODS: Two hundred ninety-five participants (82.3% women and 17.7% men) were allocated in four groups according to their fall history and functional capacity: non-fallers with higher functional capacity (NFHFC, n = 94; 69.3 ± 5.5 years), non-fallers with lower functional capacity (NFLFC, n = 114; 72.0 ± 8.1 years), fallers with higher functional capacity (FHFC, n = 29; 70.0 ± 6.0 years), and fallers with lower functional capacity (FLFC, n = 58; 72.5 ± 8.2 years). Fall history, anthropometric data, functional capacity by short physical performance battery and mobility by Timed Up and Go (TUG), and spatiotemporal gait parameters were evaluated. RESULTS: Data analysis indicated that FLFC presented the lowest scores, especially in the Five Times Sit-to-Stand Test and TUG. The PCA showed that the first principal component (PC1) explained the most substantial amount of the data variability in both walking speeds (SSWS and FWS), predominantly including temporal parameters. PC2 composed by spatial outcomes (stride and step length and walking speed) showed the highest effect size. PC1 and PC2 were able to differentiate functional status, regardless of fall history. CONCLUSIONS: Functional capacity showed great importance when analyzing gait parameters at different walking speeds (SSWS and FWS), regardless of fall history. Older adults with high functional capacity demonstrate better performance during gait. Besides, spatiotemporal parameters are the main factors explaining gait variability, both in SSWS and FWS.

Bias Voltage Dependence of Sensing Characteristics in Tunneling Magnetoresistance Sensors.

One of the characteristic features of tunneling magnetoresistance (TMR) sensors is a strong influence of bias voltage on tunneling current. Since fundamental sensing characteristics of the sensors are primarily determined by the tunneling current, the bias voltage should impact these characteristics. Previous research has indeed showed the influence of the bias voltage on the magnetic field detection and sensitivity. However, the effect has not been investigated for nonlinearity and hysteresis and the influence of bias voltage polarity has not yet been addressed. Therefore, this paper systematically investigates the dependence of field sensitivity, nonlinearity, hysteresis and magnetic field detection of CoFeB/MgO/CoFeB-based magnetoresistance sensors on bias voltage magnitude and polarity. The sensitivity and field detection of all sensors improved significantly with the bias, whereas the nonlinearity and hysteresis deteriorated. The sensitivity increased considerably (up to 32 times) and linearly with bias up to 0.6 V. The field detection also decreased substantially (up 3.9 times) with bias and exhibited the minimum values for the same magnitude under both polarities. Significant and linear increases with bias were also observed for nonlinearity (up to 26 times) and hysteresis (up to 33 times). Moreover, not only the voltage magnitude but also the polarity had a significant effect on the sensing characteristics. This significant, linear and simultaneous effect of improvement and deterioration of the sensing characteristics with bias indicates that both bias voltage magnitude and polarity are key factors in the control and modification of these characteristics.

Protective Role of Flavonoids against Intestinal Pro-Inflammatory Effects of Silver Nanoparticles.

Silver nanoparticles (AgNP) have been increasingly incorporated into food-related and hygiene products for their unique antimicrobial and preservative properties. The consequent oral exposure may then result in unpredicted harmful effects in the gastrointestinal tract (GIT), which should be considered in the risk assessment and risk management of these materials. In the present study, the toxic effects of polyethyleneimine (PEI)-coated AgNP (4 and 19 nm) were evaluated in GIT-relevant cells (Caco-2 cell line as a model of human intestinal cells, and neutrophils as a model of the intestinal inflammatory response). This study also evaluated the putative protective action of dietary flavonoids against such harmful effects. The obtained results showed that AgNP of 4 and 19 nm effectively induced Caco-2 cell death by apoptosis with concomitant production of nitric oxide, irrespective of the size. It was also observed that AgNP induced human neutrophil oxidative burst. Interestingly, some flavonoids, namely quercetin and quercetagetin, prevented the deleterious effects of AgNP in both cell types. Overall, the data of the present study provide a first insight into the promising protective role of flavonoids against the potentially toxic effects of AgNP at the intestinal level.

Pentacyanoferrate(II) complex of pyridine-4- and pyrazine-2-hydroxamic acid as source of HNO: investigation of anti-tubercular and vasodilation activities.

A pharmacophore design approach, based on the coordination chemistry of an intimate molecular hybrid of active metabolites of pro-drugs, known to release active species upon enzymatic oxidative activation, is devised. This is exemplified by combining two anti-mycobacterial drugs: pyrazinamide (first line) and delamanid (third line) whose active metabolites are pyrazinoic acid (PyzCOOH) and likely nitroxyl (HNO (or NO.)), respectively. Aiming to generate those active species, a hybrid compound was envisaged by coordination of pyrazine-2-hydroxamic acid (PyzCONHOH) with a Na3[FeII(CN)5] moiety. The corresponding pentacyanoferrate(II) complex Na4[FeII(CN)5(PyzCONHO-)] was synthesized and characterized by several spectroscopic techniques, cyclic voltammetry, and DFT calculations. Chemical oxidation of this complex with H2O2 was shown to induce the release of the metabolite PyzCOOH, without the need of the Mycobacterium tuberculosis (Mtb) pyrazinamidase enzyme (PncA). Control experiments show that both H2O2- and N-coordinated pyrazine FeII species are required, ruling out a direct hydrolysis of the hydroxamic acid or an alternative oxidative route through chelation of a metal center by a hydroxamic group. The release of HNO was observed using EPR spectroscopy in the presence of a spin trapping agent. The devised iron metal complex of pyrazine-2-hydroxamic acid was found inactive against an actively growing/non-resistant Mtb strain; however, it showed a strong dose-dependent and reversible vasodilatory activity with mostly lesser toxic effects than the reference drug sodium nitroprussiate, unveiling thus a potential indication for acute or chronic cardiovascular pathology. This is a priori a further indirect evidence of HNO release from this metal complex, standing as a possible pharmacophore model for an alternative vasodilator drug.

Nanoencapsulation of triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene from Combretum leprosum as strategy to improve its cytotoxicity against cancer cell lines.

The pentacyclic triterpene 3ß,6ß,16ß-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC50 0.11-0.26 µg mL-1) when compared with its free form (IC50 1.07-1.44 µg mL-1). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor cells.

Synergic control of action in levodopa-naïve Parkinson's disease patients: II. Multi-muscle synergies stabilizing vertical posture.

Postural instability is a major disabling feature in Parkinson's disease (PD). We quantified the organization of leg and trunk muscles into synergies stabilizing the center of pressure (COP) coordinate within the uncontrolled manifold hypothesis in levodopa-naïve patients with PD and age-matched control subjects. The main hypothesis was that changes in the synergic control of posture are present early in the PD process even before levodopa exposure. Eleven levodopa-naïve patients with PD and 11 healthy controls performed whole-body cyclical voluntary sway tasks and a self-initiated load-release task during standing on a force plate. Surface electromyographic activity in 13 muscles on the right side of the body was analyzed to identify muscle groups with parallel scaling of activation levels (M-modes). Data were collected both before ("off-drug") and approximately 60 min after the first dose of 25/100 carbidopa/levodopa ("on-drug"). COP-stabilizing synergies were quantified for the load-release task. Levodopa-naïve patients with PD showed no COP-stabilizing synergy "off-drug", whereas controls showed posture-stabilizing multi-M-mode synergy. "On-drug", patients with PD demonstrated a significant increase in the synergy index. There were no significant drug effects on the M-mode composition, anticipatory postural adjustments, indices of motor equivalence, or indices of COP variability. The results suggest that levodopa-naïve patients with PD already show impaired posture-stabilizing multi-muscle synergies that may be used as promising behavioral biomarkers for emerging postural disorders in PD. Moreover, levodopa modified synergy metrics differently in these levodopa-naïve patients compared to a previous study of patients on chronic antiparkinsonian medications (Falaki et al. in J Electromyogr Kinesiol 33:20-26, 2017a), suggesting different neurocircuitry involvement.

Synergic control of action in levodopa-naïve Parkinson's disease patients: I. Multi-finger interaction and coordination.

We explored the origin of the impaired control of action stability in Parkinson's disease (PD) by testing levodopa-naïve PD patients to disambiguate effects of PD from possible effects of long-term exposure to levodopa. Thirteen levodopa-naïve PD patients and 13 controls performed single- and multi-finger force production tasks, including producing a self-paced quick force pulse into a target. A subgroup of patients (n = 10) was re-tested about 1 h after the first dose of levodopa. Compared to controls, PD patients showed lower maximal forces and synergy indices stabilizing total force (reflecting the higher inter-trial variance component affecting total force). In addition, PD patients showed a trend toward shorter anticipatory synergy adjustments (a drop in the synergy index in preparation to a quick action) and larger non-motor equivalent finger force deviations. Lower maximal force, higher unintentional force production (enslaving) and higher inter-trial variance indices occurred in PD patients after one dosage of levodopa. We conclude that impairment in synergies is present in levodopa-naïve patients, mainly in indices reflecting stability (synergy index), but not agility (anticipatory synergy adjustments). A single dose of levodopa, however, did not improve synergy indices, as it did in PD patients on chronic anti-PD medication, suggesting a different mechanism of action. The results suggest that indices of force-stabilizing synergies may be used as an early behavioral sign of PD, although it may not be sensitive to acute drug effects in drug-naïve patients.

Point-of-care quantification of serum cellular fibronectin levels for stratification of ischemic stroke patients.

The abundance of cellular fibronectin (c-Fn) for ischemic stroke patients and the narrow time-window (<4.5 h) for the decision to administer the thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) are challenging for the development of a point-of-care (PoC) diagnostic platform. We report a case of stratification of ischemic stroke patients based on a magnetoresistive biosensor platform that quantifies the c-Fn levels in a small volume of serum, within the clinically relevant time-window. Our PoC platform uses different ratios of biofunctionalized magnetic nanoparticles (MNPs) as immunoassay labels to adjust the sensitivity within the clinically relevant ranges for c-Fn (1-4 µg/mL). After optimizing the detection range, resolution, and sensitivity, our device was able to stratify ischemic stroke patients who developed hemorrhagic transformation, the main side-effect of rtPA, from those (both non-treated and treated with rtPA) who did not.

Individual preferences in motor coordination seen across the two hands: relations to movement stability and optimality.

The framework of the uncontrolled manifold (UCM) hypothesis was used to explore variables related to stability of task performance in the two hands of young healthy individuals. Fourteen young adults performed four-finger accurate constant force production tasks interrupted by a voluntary quick force pulse production and by an externally imposed displacement of all fingers. Three groups of variables were used to quantify stability of steady force production: (1) indices of the inter-trial variance were computed within the UCM and orthogonal to the UCM; (2) indices of motor equivalence were computed between steady-state intervals separated by the force pulse and by the finger-lifting episode; and (3) referent coordinate and apparent stiffness were computed using the data during the ascending phase of the finger-lifting episode. In another task, the subjects performed accurate constant force production with visual feedback removal after the 8th second, and the drop in the total force after the removal was computed. There were differences between the right and left hand in some outcome variables such as variance within the UCM, and the timing of anticipatory synergy adjustments prior to the force pulse, consistent with the dynamic dominance hypothesis. There were significant correlations between the two hands for indices that were unrelated to accuracy of performance: variance within the UCM, index of motor equivalence, referent coordinate, apparent stiffness, and the drop of total force after visual feedback removal. We interpret these findings within the concept of stability-optimality trade-off. In particular, we conclude that individual subjects select particular, person-specific solutions within the spectrum allowed by the explicit task constraints, and this choice is consistent between the two hands. We conclude with a hypothesis that selecting specific solutions within the stability-optimality trade-off may represent an individual's personal preference consistent between the two hands.