Biosensor Strip for Rapid On-site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson's Disease.

While levodopa (L-Dopa) is the primary treatment for alleviating Parkinson's disease (PD), its efficacy is hindered by challenges such as a short half-life and inconsistent plasma levels. As PD progresses, the rising need for increased and more frequent L-Dopa doses coupled with symptom fluctuations and dyskinesias underscores the urgency for improved comprehension of the interplay between L-Dopa levels and PD motor symptoms. Addressing this critical need, we present a decentralized testing method using a disposable biosensor strip and a universal slope (U-slope) calibration-free approach. This enables reliable, rapid, simple, and cost-effective decentralized L-Dopa measurements from capillary blood. A pilot study with PD persons demonstrates the ability to monitor real-time L-Dopa pharmacokinetics from fingerstick blood after oral L-Dopa-Carbidopa (C-Dopa) tablet administration. Correlating capillary blood L-Dopa levels with PD motor scores revealed a well-defined inverse correlation with temporal motor fluctuations. We compared the resulting dynamic capillary blood L-Dopa levels with plasma L-Dopa levels using the traditional but clinically impractical high-performance liquid chromatography technique. By providing timely feedback on a proper L-Dopa dosing regimen in a decentralized and rapid fashion, this new biosensing platform will facilitate tailored optimal L-Dopa dosing, towards improving symptom management and enhancing health-related quality of life.

Attractive and repulsive effects of sensory history concurrently shape visual perception.

BACKGROUND: Sequential effects of environmental stimuli are ubiquitous in most behavioral tasks involving magnitude estimation, memory, decision making, and emotion. The human visual system exploits continuity in the visual environment, which induces two contrasting perceptual phenomena shaping visual perception. Previous work reported that perceptual estimation of a stimulus may be influenced either by attractive serial dependencies or repulsive aftereffects, with a number of experimental variables suggested as factors determining the direction and magnitude of sequential effects. Recent studies have theorized that these two effects concurrently arise in perceptual processing, but empirical evidence that directly supports this hypothesis is lacking, and it remains unclear whether and how attractive and repulsive sequential effects interact in a trial. Here we show that the two effects concurrently modulate estimation behavior in a typical sequence of perceptual tasks. RESULTS: We first demonstrate that observers' estimation error as a function of both the previous stimulus and response cannot be fully described by either attractive or repulsive bias but is instead well captured by a summation of repulsion from the previous stimulus and attraction toward the previous response. We then reveal that the repulsive bias is centered on the observer's sensory encoding of the previous stimulus, which is again repelled away from its own preceding trial, whereas the attractive bias is centered precisely on the previous response, which is the observer's best prediction about the incoming stimuli. CONCLUSIONS: Our findings provide strong evidence that sensory encoding is shaped by dynamic tuning of the system to the past stimuli, inducing repulsive aftereffects, and followed by inference incorporating the prediction from the past estimation, leading to attractive serial dependence.

Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration.

Levodopa (L-Dopa) is the "gold-standard" medication for symptomatic therapy of Parkinson disease (PD). However, L-Dopa long-term use is associated with the development of motor and non-motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L-Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch-based non-invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase-modified electrode, where sweat L-Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples.

Species Sensitivity Distributions for Nonylphenol to Estimate Soil Hazardous Concentration.

Nonylphenol is an endocrine-disrupting chemical that mimics estrogenic activity. Few studies have investigated the soil ecotoxicity of nonylphenol in the environment, based on probabilistic approaches. The present study generated soil toxicity data for nonylphenol through bioassays that determined the acute and chronic species sensitivity distributions and estimated the hazardous concentrations of nonylphenol in soil in order to protect soil ecosystems. We used eight soil-based organisms from six taxonomic groups for acute assays and five soil-based organisms from four taxonomic groups for chronic assays. The hazardous concentration values of nonylphenol in soil, based on acute and chronic species sensitivity distributions, were estimated using compiled data from the present study, as well as previous studies. This is the first study that generated sufficient data to develop species sensitivity distributions for nonylphenol in soil, and to determine hazardous concentrations of nonylphenol for soil environments.

Rapid in situ assessment for predicting soil quality using an algae-soaked disc seeding assay.

The soil quality of remediated land is altered and this land consequently exerts unexpected biological effects on terrestrial organisms. Therefore, field evaluation of such land should be conducted using biological indicators. Algae are a promising new biological indicator since they are a food source for organisms in higher soil trophic levels and easily sampled from the soil. Field evaluation of soil characteristics is preferred to be testing in laboratory conditions because many biological effects cannot be duplicated during laboratory evaluations. Herein, we describe a convenient and rapid algae-soaked disc seeding assay for assessing soil quality in the field based on soil algae. The collection of algae is easy and rapid and the method predicts the short-term quality of contaminated, remediated, and amended farm and paddy soils. The algae-soaked disc seeding assay is yet to be extensively evaluated, and the method cannot be applied to loamy sand soil in in situ evaluations. The algae-soaked disc seeding assay is recommended for prediction of soil quality in in situ evaluations because it reflects all variations in the environment. The algae-soaked disc seeding assay will help to develop management strategies for in situ evaluation.

A key role of orientation in the coding of visual motion direction.

Despite the fundamental importance of visual motion processing, our understanding of how the brain represents basic aspects of motion is incomplete. While it is generally believed that direction is the main representational feature of motion, motion processing is also influenced by nondirectional orientation signals that are present in most motion stimuli. Here, we aimed to test whether this nondirectional motion axis contributes motion perception even when orientation is completely absent from the stimulus. Using stimuli with and without orientation signals, we found that serial dependence in a simple motion direction estimation task was predominantly determined by the orientation of the previous motion stimulus. Moreover, the observed attraction profiles closely matched the characteristic pattern of serial attraction found in orientation perception. Evidently, the sequential integration of motion signals strongly depends on the orientation of motion, indicating a fundamental role of nondirectional orientation in the coding of visual motion direction.

Closing the loop for patients with Parkinson disease: where are we?

Although levodopa remains the most efficacious symptomatic therapy for Parkinson disease (PD), management of levodopa treatment during the advanced stages of the disease is extremely challenging. This difficulty is a result of levodopa's short half-life, a progressive narrowing of the therapeutic window, and major inter-patient and intra-patient variations in the dose-response relationship. Therefore, a suitable alternative to repeated oral administration of levodopa is being sought. Recent research efforts have focused on the development of novel levodopa delivery strategies and wearable physical sensors that track symptoms and disease progression. However, the need for methods to monitor the levels of levodopa present in the body in real time has been overlooked. Advances in chemical sensor technology mean that the development of wearable and mobile biosensors for continuous or frequent levodopa measurements is now possible. Such levodopa monitoring could help to deliver personalized and timely medication dosing to alleviate treatment-related fluctuations in the symptoms of PD. Therefore, with the aim of optimizing therapeutic management of PD and improving the quality of life of patients, we share our vision of a future closed-loop autonomous wearable 'sense-and-act' system. This system consists of a network of physical and chemical sensors coupled with a levodopa delivery device and is guided by effective big data fusion algorithms and machine learning methods.

Self-Testing of Ketone Bodies, along with Glucose, Using Touch-Based Sweat Analysis.

ß-Hydroxybutyrate (HB) is one of the main physiological ketone bodies that play key roles in human health and wellness. Besides their important role in diabetes ketoacidosis, ketone bodies are currently receiving tremendous attention for personal nutrition in connection to the growing popularity of oral ketone supplements. Accordingly, there are urgent needs for developing a rapid, simple, and low-cost device for frequent onsite measurements of ß-hydroxybutyrate (HB), one of the main physiological ketone bodies. However, real-time profiling of dynamically changing HB concentrations is challenging and still limited to laboratory settings or to painful and invasive measurements (e.g., a commercial blood ketone meter). Herein, we address the critical need for pain-free frequent HB measurements in decentralized settings and report on a reliable noninvasive, simple, and rapid touch-based sweat HB testing and on its ability to track dynamic HB changes in secreted fingertip sweat, following the intake of commercial ketone supplements. The new touch-based HB detection method relies on an instantaneous collection of the fingertip sweat at rest on a porous poly(vinyl alcohol) (PVA) hydrogel that transports the sweat to a biocatalytic layer, composed of the ß-hydroxybutyrate dehydrogenase (HBD) enzyme and its nicotinamide adenine dinucleotide (NAD+) cofactor, covering the modified screen-printed carbon working electrode. As a result, the sweat HB can be measured rapidly by the mediated oxidation reaction of the nicotinamide adenine dinucleotide (NADH) product. A personalized HB dose-response relationship is demonstrated within a group of healthy human subjects taking commercial ketone supplements, along with a correlation between the sweat and capillary blood HB levels. Furthermore, a dual disposable biosensing device, consisting of neighboring ketone and glucose enzyme electrodes on a single-strip substrate, has been developed toward the simultaneous touch-based detection of dynamically changing sweat HB and glucose levels, following the intake of ketone and glucose drinks.

Touch-Based Fingertip Blood-Free Reliable Glucose Monitoring: Personalized Data Processing for Predicting Blood Glucose Concentrations.

Diabetes prevalence has been rising exponentially, increasing the need for reliable noninvasive approaches for glucose monitoring. Different biofluids have been explored recently for replacing current blood finger-stick glucose strips with noninvasive painless sensing devices. While sweat has received considerable attention, there are mixed reports on correlating the sweat results with blood glucose levels. Here, we demonstrate a new rapid and reliable approach that combines a simple touch-based fingertip sweat electrochemical sensor with a new algorithm that addresses for personal variations toward the accurate estimate of blood glucose concentrations. The new painless and simple glucose self-testing protocol leverages the fast sweat rate on the fingertip for rapid assays of natural perspiration, without any sweat stimulation, along with the personalized sweat-response-to-blood concentration translation. A reliable estimate of the blood glucose sensing concentrations can thus be realized through a simple one-time personal precalibration. Such system training leads to a substantially improved accuracy with a Pearson correlation coefficient higher than 0.95, along with an overall mean absolute relative difference of 7.79%, with 100% paired points residing in the A + B region of the Clarke error grid. The speed and simplicity of the touch-based blood-free fingertip sweat assay, and the elimination of periodic blood calibrations, should lead to frequent self-testing of glucose and enhanced patient compliance toward the improved management of diabetes.

Touch-Based Stressless Cortisol Sensing.

Tracking fluctuations of the cortisol level is important in understanding the body's endocrine response to stress stimuli. Traditional cortisol sensing relies on centralized laboratory settings, while wearable cortisol sensors are limited to slow and complex assays. Here, a touch-based non-invasive molecularly imprinted polymer (MIP) electrochemical sensor for rapid, simple, and reliable stress-free detection of sweat cortisol is described. The sensor readily measures fingertip sweat cortisol via highly selective binding to the cortisol-imprinted electropolymerized polypyrrole coating. The MIP network is embedded with Prussian blue redox probes that offer direct electrical signaling of the binding event to realize sensitive label-free amperometric detection. Using a highly permeable sweat-wicking porous hydrogel, instantaneously secreted fingertip sweat can be conveniently and rapidly collected without any assistance. By eliminating time lags, such rapid (3.5 min) fingertip assay enables the capture of sharp variations in cortisol levels, compared to previous methods. Such advantages are demonstrated by tracking cortisol response in short cold-pressor tests and throughout day-long circadian rhythm, along with gold-standard immunoassay validation. A stretchable epidermal MIP sensor is also described for directly tracking cortisol in exercise-induced sweat. The rapid touch-based cortisol sensor offers an attractive, accessible, stressless avenue for quantitative stress management.

A self-sustainable wearable multi-modular E-textile bioenergy microgrid system.

Despite the fast development of various energy harvesting and storage devices, their judicious integration into efficient, autonomous, and sustainable wearable systems has not been widely explored. Here, we introduce the concept and design principles of e-textile microgrids by demonstrating a multi-module bioenergy microgrid system. Unlike earlier hybrid wearable systems, the presented e-textile microgrid relies solely on human activity to work synergistically, harvesting biochemical and biomechanical energy using sweat-based biofuel cells and triboelectric generators, and regulating the harvested energy via supercapacitors for high-power output. Through energy budgeting, the e-textile system can efficiently power liquid crystal displays continuously or a sweat sensor-electrochromic display system in pulsed sessions, with half the booting time and triple the runtime in a 10-min exercise session. Implementing "compatible form factors, commensurate performance, and complementary functionality" design principles, the flexible, textile-based bioenergy microgrid offers attractive prospects for the design and operation of efficient, sustainable, and autonomous wearable systems.

Temporal Dynamics of Visual Attention Allocation.

We often temporally prepare our attention for an upcoming event such as a starter pistol. In such cases, our attention should be properly allocated around the expected moment of the event to process relevant sensory input efficiently. In this study, we examined the dynamic changes of attention levels near the expected moment by measuring contrast sensitivity to a target that was temporally cued by a five-second countdown. We found that the overall attention level decreased rapidly after the expected moment, while it stayed relatively constant before it. Results were not consistent with the predictions of existing explanations of temporal attention such as the hazard rate or the stimulus-driven oscillations. A control experiment ruled out the possibility that the observed pattern was due to biased time perception. In a further experiment with a wider range of cue-stimulus-intervals, we observed that attention level increased until the last 500 ms of the interval range, and thereafter, started to decrease. Based on the performances of a generative computational model, we suggest that our results reflect the nature of temporal attention that takes into account the subjectively estimated hazard rate and the probability of relevant events occurring in the near future.

The effects of silver nanomaterial shape and size on toxicity to Caenorhabditis elegans in soil media.

Silver nanomaterials (AgNMs) of various shapes and sizes are manufactured for different purposes and used as ingredients in a wide variety of products and applications. Recently, the toxicity of AgNMs has attracted significant attention. However, the effect of the shape of AgNMs (particles, wires, plates) on their toxicity in soil ecosystems remains poorly understood. In this study, we added AgNMs of different shapes and sizes (silver nanoparticles, AgNPs; 10 µm silver nanowires, 10-AgNWs; 20 µm silver nanowires, 20-AgNWs; silver nanoplates, AgPLs) to natural soil and determined their effect on the growth and reproduction of the free-living nematode, Caenorhabditis elegans. AgNPs and AgPLs were found to inhibit the growth and reproduction of C. elegans, whereas AgNWs had a negligible effect. Among these AgNMs, the results of this study suggest AgNPs are the most toxic. This confirms that the shape of AgNPs plays a significant role in their toxicity level. To the best of our knowledge, this is the first comparative analysis of the shape-dependent toxicity of AgNMs in the soil using nematode C. elegans. This study provides a scientific reference for assessing shape-dependent soil nanotoxicity.

Simultaneous detection of ATP metabolites in human plasma and urine based on palladium nanoparticle and poly(bromocresol green) composite sensor.

A sensitive voltammetric sensor based on palladium nanoparticles (PdNPs) and poly-bromocresol green (pBG) composite layer immobilized on amide functionalized single-walled carbon nanotubes (AmSWCNTs) modified pyrolytic graphite (PdNPs:pBG/AmSWCNTs/PG) has been prepared for the simultaneous determination of adenosine triphosphate (ATP) catabolites, inosine (INO), hypoxanthine (HX), xanthine (XT), and uric acid (UA). The modified PdNPs:pBG/AmSWCNTs/PG was characterized by electrochemical experiments and surface analysis, which exhibited exceptional electrocatalytic effects towards the oxidation of INO, HX, XT, and UA with a significant enhanced peak current and well resolved peaks separation for all the analytes. The linear calibration curves were obtained in the concentration range of 0.001-175 µM, 0.001-200 µM, 0.001-150 µM, and 0.001-200 µM and limits of detection were found as 0.95 nM, 1.04 nM, 1.07 nM, and 0.43 nM corresponding to INO, HX, XT, and UA, respectively. The common metabolites present in the biological fluids did not interfere in the determination. The applicability of the proposed sensor was successfully demonstrated by determining INO, HX, XT, and UA in the human plasma and urine and the obtained results were validated by using HPLC.

Soil ecotoxicity study of DEHP with respect to multiple soil species.

Di (2-ethylhexyl) phthalate or DEHP is classified as an endocrine-disrupting chemical. It is used as a plasticizer and pesticide additive. Moreover, it has a half-life of about 150-300 days. Thus, it is present in the soil environment and soil risk assessments for DEHP are needed. However, a number of studies have focused on the effects of DEHP in a single soil species. In this study, we conducted acute and chronic toxicity testing for DEHP using varied soil species, including plants, earthworms, soil algae, Collembola, and soil nematodes. In the plant toxicity test, no effect was observed at very high concentration except at some endpoints, and no effect was observed in the earthworm toxicity test. However, there were adverse effects on soil algae, Collembola, and nematodes. Notably, in the Collembola assays, the survival of adults decreased significantly at very high concentrations, whereas reproduction was hindered at low concentrations. Similar inhibition of reproduction was noted in the soil nematode assay. This suggests that DEHP has a greater influence on fertility than survival in the adult test species. However, besides hindered reproduction, no effect was observed on soil species at environmentally relevant concentrations.

Separation detection of hemoglobin and glycated hemoglobin fractions in blood using the electrochemical microfluidic channel with a conductive polymer composite sensor.

Separation and detection of hemoglobin (Hb) and glycated hemoglobin fractions (HbA1c, HbAld1+2, HbAle, HbAld3a, HbAla+b, HbA2, and HbAld3b) was performed using an electrochemical AC field modulated separation channel (EMSC) coupled with a sensor probe. The sensor was fabricated based on immobilization of a redox mediator on the poly(2,2':5',5″-terthiophene-3'-p-benzoic acid, pTTBA) and N,S-doped porous carbon (NSPC) nanocomposite. The different types of catalytic redox mediators such as Nile Blue (NB), toluidine blue O (TBO), and Neutral Red (NR) were evaluated to achieve the efficient detection. Of these, the NB-based sensor showed the best analytical signal for Hb and HbA1c, thus it was characterized using various electrochemical and surface analysis methods. After that, the sensor was coupled with the EMSC to achieve the separation detection of the Hb family. The frequency and amplitude of the AC electrical field applied onto the EMSC walls were the main driving forces for the separation and sensitive detection of the analytes. Under optimized conditions, linear dynamic ranges for Hb and HbA1c among their fractions were obtained between 1.0 × 10-6 to 3.5 mM and 3.0 × 10-6 to 0.6 mM with the detection limit of 8.1 × 10-7 ± 3.0 × 10-8 and 9.2 × 10-7 ± 5 × 10-8 mM, respectively. Interference effects of other biomolecules were also investigated and the clinical applicability of the device was evaluated by the determination of total Hb and % HbA1c in real human blood samples.

Matricidal hatching can induce multi-generational effects in nematode Caenorhabditis elegans after dietary exposure to nanoparticles.

In this study, we investigated multi-generational effects and generation particle transfer in Caenorhabditis elegans following maternal food exposure to core-shell quantum dots. We found that that the Bag of Worms (BOW) phenotype in aged worms induces changes in quantum dot distribution in the parental body, which is related to the inter-generation transfer of these nanoparticles and to their effects in the offspring. To confirm these results we examined a variety of endpoints, namely, survival, reproduction, aging phenotype, oxidative stress, and intestinal fat metabolism. We show that worms born to parents at different times after exposure show different phenotypic effects as a consequence of quantum dot transfer. This evidence of trans-generational transfer and the effects of nanoparticles highlights the complex multi-generational effects and potential safety hazards that can occur under real environmental conditions.

Ecological hazard assessment of methyl ethyl ketone using the species sensitivity distribution approach in a soil ecosystem.

Methyl ethyl ketone (MEK) is a common and widely used industrial solvent. However, few studies have investigated its toxicity, or its effects as a contaminant in soil ecosystems. In this study, acute and chronic toxicity data for MEK were generated, and ecological risk based on a species sensitivity distribution was assessed. Seven soil organisms from six taxonomic groups were used for acute toxicity tests and five soil organisms from four taxonomic groups were used for chronic toxicity tests. Acute and chronic soil HC5 (hazardous concentration for 5% of species) values for MEK were estimated as 53.04 and 2.593 mg MEK/kg dry soil, respectively. This is the first study to conduct battery testing for MEK; it specifies hazardous concentrations, warns of the need for accident preparedness, and points to serious potential hazards of MEK at various levels of the soil ecosystem which can translate into greater environmental damage with implications for human health. The specific sensitivity levels determined may serve as a benchmark for establishing soil standards and strategies for ecosystem protection in the face of accidental contamination.

Magnetic force assisted electrochemical sensor for the detection of thrombin with aptamer-antibody sandwich formation.

A magnetic force assisted electrochemical aptamer-antibody sandwich assay (MESA) was developed for the detection of thrombin as a model protein in serum samples. The MESA using the formation of sandwich complexes on the electrochemical sensor probe for reaction and the removal of unbound bioconjugates from the sensor surface without washing are controlled by a magnetic field. Thrombin was determined by the cathodic currents of a toluidine blue O (TBO) attached with thrombin antibody modified magnetic nanoparticle (MNP) at the sensor surface. To detect thrombin in a serum sample, we applied a thrombin-specific aptamer as the capture molecule bound to the functionalized conducting polymer layer (poly-(2,2´:5´,5″-terthiophene-3´-p-benzoic acid) (pTBA)), and streptavidin and starch coated-MNP was conjugated with biotinylated thrombin antibodies (Ab) and TBO as the bioconjugate (MNP@Ab-TBO). The characterization of MNP@Ab-TBO and sensor probe was performed using voltammetry, impedance spectroscopy, XPS, and UV-VIS spectroscopy. The experimental conditions were optimized in terms of pH, binding time, removal time of unbound bioconjugates, and applied potential. The dynamic ranges of thrombin were from 1.0 to 500 nM with detection limit of 0.49 ( ±â€¯0.06) nM. The recovery test demonstrates the reliability of the proposed sensing system for a handheld device.