RESUMEN

The pollen wall protects pollen during dispersal and is critical for pollination recognition. In the Poaceae family, the pollen exine stereostructure exhibits a high degree of conservation with similar patterns across species. However, there remains controversy regarding the conservation of key factors involved in its formation among various Poaceae species. EPAD1, as a gene specific to the Poaceae family, and its orthologous genes play a conserved role in pollen wall formation in wheat and rice. However, they do not appear to have significant functions in maize. To further confirm the conserved function of EPAD1 in Poaceae, we performed an analysis on four EPAD1 orthologs from two distinct sub-clades within the Poaceae family. The two functional redundant barley EPAD1 genes (HvEPAD1 and HvEPAD2) from the BOP clade, along with the single copy of sorghum (SbEPAD1) and millet (SiEPAD1) from the PACMAD clade were examined. The CRISPR-Cas9-generated mutants all exhibited defects in pollen wall formation, consistent with previous findings on EPAD1 in rice and wheat. Interestingly, in barley, hvepad2 single mutant also showed apical spikelets abortion, aligning with a decreased expression level of HvEPAD1 and HvEPAD2 from the apical to the bottom of the spike. Our finding provides evidence that EPAD1 orthologs contribute to Poaceae specific pollen exine pattern formation via maintaining primexine integrity despite potential variations in copy numbers across different species.

Asunto(s)

RESUMEN

Monkeypox virus (MPXV) infection was classified as a public health emergency of international concern by the World Health Organization (WHO) in 2022, being transmitted between humans by large respiratory droplets, in contact with skin lesions, fomites, and sexually. Currently, there are no available accessible and simple-to-use diagnostic tests that accurately detect MPXV antigens for decentralized and frequent testing. Here, we report an electrochemical biosensor to detect MPXV antigens in saliva and plasma samples within 15 min using accessible materials. The electrochemical system was manufactured onto a paper substrate engraved by a CO2 laser machine, modified with gold nanostructures (AuNS) and a monoclonal antibody, enabling sensitive detection of A29 viral protein. The diagnostic test is based on the use of electrochemical impedance spectroscopy (EIS) and can be run by a miniaturized potentiostat connected to a smartphone. The impedimetric biosensing method presented excellent analytical parameters, enabling the detection of A29 glycoprotein in the concentration ranging from 1 × 10-14 to 1 × 10-7 g mL-1, with a limit of detection (LOD) of 3.0 × 10-16 g mL-1. Furthermore, it enabled the detection of MPXV antigens in the concentration ranging from 1 × 10-1 to 1 × 104 PFU mL-1, with an LOD of 7.8 × 10-3 PFU mL-1. Importantly, no cross-reactivity was observed when our device was tested in the presence of other poxvirus and nonpoxvirus strains, indicating the adequate selectivity of our nanobiosensor for MPXV detection. Collectively, the nanobiosensor presents high greenness metrics associated with the use of a reproducible and large-scale fabrication method, an accessible and sustainable paper substrate, and a low volume of sample (2.5 µL), which could facilitate frequent testing of MPXV at point-of-care (POC).

Asunto(s)

RESUMEN

We developed a novel, compact, three-dimensional electrochemical paper-based analytical device (3D-ePAD) for patulin (PT) determination. The selective and sensitive PT-imprinted Origami 3D-ePAD was constructed based on a graphene screen-printed electrode modified with manganese-zinc sulfide quantum dots coated with patulin imprinted polymer (Mn-ZnS QDs@PT-MIP/GSPE). The Mn-ZnS QDs@PT-MIP was synthesized using 2-oxindole as the template, methacrylic acid (MAA) as a monomer, N,N'-(1,2-dihydroxyethylene) bis (acrylamide) (DHEBA) as cross-linker and 2,2'-azobis (2-methylpropionitrile) (AIBN) as initiator, respectively. The Origami 3D-ePAD was designed with hydrophobic barrier layers formed on filter paper to provide three-dimensional circular reservoirs and assembled electrodes. The synthesized Mn-ZnS QDs@PT-MIP was quickly loaded on the electrode surface by mixing with graphene ink and then screen-printing on the paper. The PT-imprinted sensor provides the greatest enhancement in redox response and electrocatalytic activity, which we attributed to synergetic effects. This arose from an excellent electrocatalytic activity and good electrical conductivity of Mn-ZnS QDs@PT-MIP, which improved electron transfer between PT and the electrode surface. Under the optimized DPV conditions, a well-defined PT oxidation peak appears at +0.15 V (vs Ag/AgCl) using 0.1 M of phosphate buffer (pH 6.5) containing 5 mM K3Fe(CN)6 as the supporting electrolyte. Our developed PT imprinted Origami 3D-ePAD revealed excellent linear dynamic ranges of 0.001-25 µM, with a detection limit of 0.2 nM. Detection performance indicated that our Origami 3D-ePAD possesses outstanding detection performance from fruits and CRM in terms of high accuracy (%Error for inter-day is 1.11%) and precision (%RSD less than 4.1%). Therefore, the proposed method is well-suited as an alternative platform for ready-to-use sensors in food safety. The imprinted Origami 3D-ePAD is an excellent disposable device with a simple, cost-effective, and fast analysis, and it is ready to use for determining patulin in actual samples.

RESUMEN

We evaluated pressure-based right ventricular ejection fraction (RVEF) and diastolic isovolumetric relaxation time constant (Tau) from continuously (up to 30 days) invasive measured right ventricular pressures in mechanically ventilated patients with severe COVID-19 acute respiratory distress syndrome (ARDS). We retrospectively calculated beat-to-beat ejection fraction from right ventricular pressures and dp/dt maximum and minimum in 39 patients treated between October 1st, 2020 and June 30th, 2021. After performing a stepwise logistic regression with survival as a dependent variable, we divided the patients into survivors and nonsurvivors based on their 60-day mortality. Independent outcome variables were the values of RVEF and Tau over time after insertion of the right ventricular probe along with right ventricular systolic and diastolic pressures (RVSP) and the estimated pulmonary artery diastolic pressure (ePAD). RVEF increased significantly over time in the survivors (estimate: 0.354; 95% confidence interval, CI: 0.18-0.53; p < 0.001) but remained unchanged in the nonsurvivors. Tau increased significantly in the nonsurvivors (estimate: 0.001; 95% CI: 0.0004-0.0018; p < 0.002) but not in the survivors. On the last measurement day, RVSP and ePAD were significantly lower while RVEF was significantly higher in the survivors compared to the nonsurvivors. In COVID-19 ARDS patient's, calculation of beat-to-beat RVEF and Tau from continuously invasive measured right ventricular pressures seems to unravel contrary trends in RVEF with an increase in the surviving and a decrease in the nonsurviving patients. Tau remained unchanged in the surviving but increased in the nonsurviving patients over time.

RESUMEN

Since the inception of the first electrochemical devices on paper substrates, many different reports of microfluidic paper-based electroanalytical devices (µPEDs), innovative hydrophobic barriers and electrode fabrication processes have allowed the incorporation of diverse materials, resulting in different applications and a boost in performance. These advancements have led to the creation of paper-based devices with comparable performance to many standard conventional devices, with the added benefits of pumpless fluidic transport, component separation and reagent storage that can be exploited to automate and handle sample preprocessing. Herein, we review µPEDs, summarize the characteristics and functionalities of µPEDs, such as separation, fluid flow control and storage, and outline the conventional and emerging fabrication and modification approaches for µPEDs. We also examine the recent application of µPEDs in biomedicine, the environment, and food and water safety, as well as some limitations and challenges that must be addressed.

Asunto(s)

RESUMEN

In this work, we present a novel self-powered approach totally independent from any external energy source. We have developed a self-powered paper-based immunosensor that generates energy in the presence of the biomarker in the sample. In particular, the device - which has been labeled as Immuno-Battery - makes use of magnesium as anode and the widely employed HRP-labeled antibody as cathodic catalyst to detect C-reactive protein (CRP) presence in artificial samples. Feasibility of self-powered sensing is proved by submitting the immuno-battery to a resistive load. In this regime, the sensor provides operation voltages above 1.55 V and maximum power densities from 40 to 571 µW cm-2 that allow for future implementation of an electronic readout circuit. We have demonstrated that sensitivity of the system is not compromised by the self-powered mode operation, as the LOD value delivered by our battery (20 ± 2 ng mL-1) is compliant with LOD values reported for protein detection in paper-based electrochemical immunoassays with chronoamperometric methods. Moreover, as a case study, a LOD of 269 ± 39 ng mL-1 is obtained for CRP detection, in accordance with available commercial high-sensitivity CRP detection kits. This proof-of-concept opens the path towards the development of digital diagnostic devices in a sustainable and affordable manner.

Asunto(s)

RESUMEN

Introduction: We aimed to determine the independent association between sleep quality and Alzheimer's disease (AD) biomarkers, and whether the associations differ with age. Methods: We included 1240 individuals aged ≥50, without dementia from the European Prevention of Alzheimer's Disease v1500.0 dataset. Linear regression was used to examine Pittsburgh Sleep Quality Index (PSQI) scores against cerebrospinal fluid (CSF) phosphorylated tau/ß-amyloid ratio (p-tau/Aß42) for the entire sample and via age tertiles. Models controlled for demographic, clinical, genetic, vascular, and neuroimaging variables. Results: For the youngest age tertile, shorter sleep duration and higher sleep efficiency were associated with greater p-tau/Aß42 ratio. For the oldest tertile, longer sleep latency was associated with greater p-tau/Aß42. Discussion: Differential relationships between sleep and AD pathology depend on age. Short sleep duration and sleep efficiency are relevant in middle age whereas time taken to fall asleep is more closely linked to AD biomarkers in later life. Highlights: This study shows age differences in the link between sleep and AD biomarkers.Shorter sleep was associated with greater p-tau/Aß42 ratio in middle age.The association was independent of genetic, vascular, and neuroimaging markers of AD.

RESUMEN

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI preprocessing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses.

Asunto(s)

RESUMEN

Laser-induced graphene (LIG) on paper substrates is a desirable material for single-use point-of-care sensing with its high-quality electrical properties, low fabrication cost, and ease of disposal. While a prior study has shown how the repeated lasing of substrates enables the synthesis of high-quality porous graphitic films, however, the process-property correlation of lasing process on the surface microstructure and electrochemical behavior, including charge-transfer kinetics, is missing. The current study presents a systematic in-depth study on LIG synthesis to elucidate the complex relationship between the surface microstructure and the resulting electroanalytical properties. The observed improvements were then applied to develop high-quality LIG-based electrochemical biosensors for uric acid detection. We show that the optimal paper LIG produced via a dual pass (defocused followed by focused lasing) produces high-quality graphene in terms of crystallinity, sp2 content, and electrochemical surface area. The highest quality LIG electrodes achieved a high rate constant k0 of 1.5 × 10-2 cm s-1 and a significant reduction in charge-transfer resistance (818 Ω compared with 1320 Ω for a commercial glassy carbon electrode). By employing square wave anodic stripping voltammetry and chronoamperometry on a disposable two-electrode paper LIG-based device, the improved charge-transfer kinetics led to enhanced performance for sensing of uric acid with a sensitivity of 24.35 ± 1.55 µA µM-1 and a limit of detection of 41 nM. This study shows how high-quality, sensitive LIG electrodes can be integrated into electrochemical paper analytical devices.

Asunto(s)

RESUMEN

In this study, we report on a novel aptasensor based on an electrochemical paper-based analytical device (ePAD) that employs a tungsten disulfide (WS2)/aptamer hybrid for the detection of Listeria monocytogenes. Listeria is a well-known causative pathogen for foodborne diseases. The proposed aptasensor signifies many lucrative features which include simple, cost-effective, reliable, and disposable. Furthermore, the use of an aptamer added more advantageous features in the biosensor. The morphological, optical, elemental composition, and phase properties of the synthesized tungsten disulfide (WS2) nanostructures were characterized by field-emission scanning electron microscopy (FESEM), RAMAN spectroscopy, photoluminescence (PL), and X-ray diffraction (XRD), while electrochemical impedance spectroscopy was performed to corroborate the immobilization of aptamer and to assess the L. monocytogenes sensing performance. The limit of detection (LoD) and limit of quantification (LoQ) of the aptasensor was found to be 10 and 4.5 CFU/mL, respectively, within a linear range of 101-108 CFU/mL. The proposed sensor was found to be selective solely towards Listeria monocytogenes in the presence of various bacterial species such as Escherichia coli and Bacillus subtilis. Validation of the aptasensor operation was also evaluated in real samples by spiking them with fixed concentrations (101, 103, and 105) of Listeria monocytogenes, thereby, paving the way for its potential in a point-of-care scenario.

Asunto(s)

RESUMEN

Electrophoretic deposition (EPD) has been recognized as a promising large-scale film preparation technology for industrial application. Inspired by the conventional EPD method and the crystal diffusion growth strategy, we propose a modified electrophoretic-induced self-assembly deposition (EPAD) technique to control the morphologies of organic functional materials. Here, an ionic-type dye with a conjugated skeleton and strong noncovalent interactions, celestine blue (CB), is chosen as a module molecule for EPAD investigation. As expected, CB molecules can assemble into different nanostructures, dominated by applied voltage, concentration effect, and duration. Compared to a nanopillar layered packing structure formed by the traditional spin-coating method, the EPAD approach can produce a nanofiber structure under a fixed condition of 10 V/10 min. Intriguingly, a memristor device based on a pillar-like nanostructure exhibits WORM-type behavior, while a device based on nanofibers presents Flash memory performance. The assemble process and the memory mechanism are uncovered by molecular dynamics simulations and density-functional theory (DFT) calculations. This work endows the typical EPD technique with a fresh application scenario, where an in-depth study on the growth mechanism of nanofibers and the positive effect of unique morphologies on memristor performance are offered.

RESUMEN

AIMS: We continuously monitored right ventricular pressures and the estimated diastolic pulmonary artery pressure (ePAD) for up to 30 days in mechanically ventilated patients with severe COVID-19 acute respiratory distress syndrome in order to detect and treat right ventricular and pulmonary artery hypertension. METHODS AND RESULTS: We retrospectively evaluated right ventricular pressures and the ePAD measured in 30 invasively ventilated COVID-19 acute respiratory distress syndrome patients between 1 October 2020 and 31 March 2021. We divided the patients into two groups, survivors and non-survivors based on their 60 day mortality. Primary outcome variables were the values of right ventricular pressures and the ePAD over time after insertion of the right ventricular probe. Right ventricular systolic pressure [RVSP, (IQR; 25th to 75th percentile)] was significantly lower on the first and the last measurement day in the survivors compared with the non-survivors [Day 1: 38 (27-45) vs. 46 (44-49), P = 0.036; last day: 36 (27-44) vs. 51 (40-57) mmHg, P = 0.006]. 16/22 survivors and 7/8 non-survivors received sildenafil orally, one survivor received additionally inhaled nitric oxide and one survivor and one non-survivor each inhaled iloprost. On the last measurement day, both right ventricular pressure amplitude [31 (26-37) vs. 38 (35-47) mmHg, P = 0.027] and ePAD [22 (16-26) vs. 31 (23-34) mmHg, P = 0.043] were significantly lower in the survivors compared with the non-survivors. Four patients in the survivor group developed excessive high RVSP in the course of their disease (peak: 57/61/78/105 mmHg). After sildenafil 20 mg every 8 h, additional inhaled nitric oxide (20 ppm) in one and additional inhaled iloprost 20 µg every 4 h in another patient RVSP consecutively decreased substantially in all four patients until the end of the measurement period (47/23/42/47 mmHg). CONCLUSIONS: The RVSP and right ventricular pressure amplitude both were significantly lower in the survivors compared with those in the non-survivors with a significant decrease in RVSP over time in the survivors suggesting successful lowering by pulmonary vasodilators. The ePAD as an indicator of left heart failure was significantly higher in non-survivors compared to the surviving patients.

Asunto(s)

RESUMEN

The sensing field has shed light on an urgent necessity for field-deployable, user-friendly, sensitive, and scalable platforms that are able to translate solutions into the real world. Here, we attempt to meet these requests by addressing a simple, low-cost, and fast electrochemical approach to provide sensitive assays that consist of dropping a small volume (0.5 µL) of off-the-shelf alcohols on pyrolyzed paper-based electrodes before adding the sample (150 µL). This method was applied in the detection of phosphate after the formation of the phosphomolybdate complex (250-860 nm in size). Prior drops of isopropanol allow for the fast penetration of the sample through pores of this hydrophobic paper, delivering hindrance-free redox reactions across increasing active areas and ultimately improving the detection performance. The sensitivity (-1.9 10-6 mA cm-2 ppb-1) and limit of detection (1.1 ppb) were improved, respectively, by factors of 33 and 99 over the data achieved without the addition of isopropanol, listing among the lowest values when compared with those results reported in the literature for phosphate (expressed in terms of the concentration of phosphorus). The approach enabled the quantification of this analyte in real samples with accuracies ranging from 87 to 103%. Furthermore, preliminary measurements demonstrated the successful performance of the electrodes with prior addition of other widely used alcohols, that is, methanol and ethanol. These results may extend the applicability of the method. In special, the scalability and eco-friendly character of the electrode fabrication combined with the sensitivity and simplicity of the analyses make the developed platform a promising alternative that may help to pave the way for a new generation of disposable sensors toward the daily monitoring of phosphate in water samples, thus contributing to prevent ecological side effects.

Asunto(s)

RESUMEN

BACKGROUND: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. MATERIALS AND METHODS: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid beta (Aß)1-42 and 27 pg/mL for p-tau181 were validated using Gaussian mixture models. Given strong correlation of p-tau and t-tau (R2  = 0.98, P < 0.001), neurodegeneration was defined by age-adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages. RESULTS: Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A-T-N-, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non-Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T-N- compared to A-T-N- (P < 0.001). DISCUSSION: In non-demented individuals along the AD continuum, p-tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.

Asunto(s)

RESUMEN

BACKGROUND: The European Prevention of Alzheimer's Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer's dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer's dementia. OBJECTIVES: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. DESIGN: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). SETTING: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. PARTICIPANTS: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. MEASUREMENTS: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer's disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. RESULTS: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid -, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. CONCLUSIONS: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.

Asunto(s)

RESUMEN

A second opinion about cancer stage is crucial when clinicians assess patient treatment progress. Staging is a process that takes into account description, location, characteristics, and possible metastasis of tumors in a patient. It should follow standards, such as the TNM Classification of Malignant Tumors. However, in clinical practice, the implementation of this process can be tedious and error prone. In order to alleviate these problems, we intend to assist radiologists by providing a second opinion in the evaluation of cancer stage. For doing this, we developed a TNM classifier based on semantic annotations, made by radiologists, using the ePAD tool. It transforms the annotations (stored using the AIM format), using axioms and rules, into AIM4-O ontology instances. From then, it automatically calculates the liver TNM cancer stage. The AIM4-O ontology was developed, as part of this work, to represent annotations in the Web Ontology Language (OWL). A dataset of 51 liver radiology reports with staging data, from NCI's Genomic Data Commons (GDC), were used to evaluate our classifier. When compared with the stages attributed by physicians, the classifier stages had a precision of 85.7% and recall of 81.0%. In addition, 3 radiologists from 2 different institutions manually reviewed a random sample of 4 of the 51 records and agreed with the tool staging. AIM4-O was also evaluated with good results. Our classifier can be integrated into AIM aware imaging tools, such as ePAD, to offer a second opinion about staging as part of the cancer treatment workflow.

Asunto(s)

RESUMEN

The adulteration of herbal medicines by dexamethasone or prednisolone is regarded as a serious problem in many communities. Herein, a novel platform for the separation and quantification of both target steroids in herbal medicines based on electrochemical paper-based analytical devices (ePADs) has been created. The ePAD was composed of Whatman SG81 chromatography paper, 3D-printed devices and a commercial screen-printed electrode. Whatman SG81 silica-coated paper was used for the separation of dexamethasone and prednisolone based on the difference in their partition coefficients during the flow of the mobile phase. The optimal mobile phase was composed of 60% ethyl acetate in cyclohexane and required 7 min for separation. The separated steroids on the paper were then quantified by electrochemical detection using differential pulse voltammetry, in which the 3D-printed devices facilitated the measurement. Analytical detection ranges of 10-500 µg mL-1 were obtained for both dexamethasone and prednisolone (r2 = 0.988 and 0.994, respectively). The limits of detection for dexamethasone and prednisolone were 3.59 and 11.98 µg mL-1, respectively, whereas the limits of quantification were 6.00 and 20.02 µg mL-1, respectively. The amounts of both target steroids derived from real herbal medicine samples determined by the proposed method were comparable to those obtained with assays using standard high-performance liquid chromatography. In addition, a simple evaporation step can be used to increase the concentration of the samples before analysis. These ePADs are simple, low-cost, rapid, and very promising for on-site quantitative detection.

Asunto(s)

RESUMEN

Herein, we propose a highly sensitive and selective three-dimensional electrochemical paper-based analytical device (3D-ePAD) to determine serotonin (Ser). It uses a graphite-paste electrode modified with nanoparticles coated with molecularly imprinted polymer (MIP). Fe3O4@Au nanoparticles were encapsulated with silica to create novel nano-sized MIP. Morphology and structural characterization reveal that silica imprinted sites (Fe3O4@Au@SiO2) synthesized via sol-gel methods provide excellent features for Ser detection, including high porosity, and greatly improve analyte diffusion and adsorption to provide a faster response by the MIP sensor. The template molecule was effectively removed by solvent extraction to provide a greater number of specific cavities that enhance analyte capacity and sensitivity. The 3D-ePAD was fabricated by alkyl ketene dimer (AKD)-inkjet printing of a circular hydrophobic detection zone on filter paper for application of aqueous samples, coupled with screen-printed electrodes on the paper, which was folded underneath the hydrophobic zone. The sensor was constructed by drop coating of Fe3O4@Au@SiO2-MIP nanocomposites on the graphite electrode (GPE) surface. The MIP sensor (Fe3O4@Au@SiO2-MIP/GPE) was used in the detection of Ser by linear-sweep voltammetry (LSV) in 0.1 M phosphate buffer at pH 8.0. The device exhibits high sensitivity toward Ser, which we attribute to synergistic effects between catalytic properties, electrical conductivity of Fe3O4@Au@SiO2, and significantly increased numbers of imprinted sites. Ser oxidation was observed at +0.39 V. Anodic peak currents for Ser show linearity from 0.01 to 1000 µM (y = 0.0075 ± 0.0049 x + 0.4071 ± 0.0052, r2 = 0.993), with a detection limit of 0.002 µM (3S/N). The device provides good repeatability (%relative standard deviations; RSD) = 4.23%, calculated from the current responses of ten different MIP sensors). The device also exhibits high selectivity and reproducibility (%RSD = 8.35%, obtained from five calibration plots). The analytical performance of the device is suitable for the determination of Ser in pharmaceutical capsules and urine samples.

Asunto(s)

RESUMEN

INTRODUCTION: It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach. METHODS: A virtual registry, with access to risk factors and biomarkers for AD through minimal data sets of ongoing cohort studies, was set up. RESULTS: To date, ten cohorts have been included in the EPAD. Around 2500 participants have been selected, using variables associated with the risk for AD. Of these, 15% were already recruited in the EPAD longitudinal cohort study, which serves as a trial readiness cohort. DISCUSSION: This study demonstrates that a virtual registry can be used for the preselection of participants for AD studies.

Asunto(s)

RESUMEN

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

Asunto(s)