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The exploration into nanomaterial-based nonenzymatic biosensors with superb performance in terms of good sensitivity and anti-interference ability in disease marker monitoring has always attained undoubted priority in sensing systems. In this work, we report the design and synthesis of a highly active nanocatalyst, i.e., palladium and platinum nanoparticles (Pt&Pd-NPs) decorated ultrathin nanoporous gold (NPG) film, which is modified on a homemade graphene paper (GP) to develop a high-performance freestanding and flexible nanohybrid electrode. Owing to the structural characteristics the robust GP electrode substrate, and high electrochemically catalytic activities and durability of the permeable NPG support and ultrafine and high-density Pt&Pd-NPs on it, the resultant Pt&Pd-NPs-NPG/GP electrode exhibits excellent sensing performance of low detection limitation, high sensitivity and anti-interference capability, good reproducibility and long-term stability for the detection of small molecular biomarkers hydrogen peroxide (H 2 O 2 ) and glucose (Glu), and has been applied to the monitoring of H 2 O 2 in different types of live cells and Glu in body fluids such as urine and fingertip blood, which is of great significance for the clinical diagnosis and prognosis in point-of-care testing.

Aβ 42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer's disease (AD). Because of the heterogeneity and transient nature of Aβ 42 oligomers (Aβ 42 Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ 42 monomers (Aβ 42 Ms) and Aβ 42 Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ 42 ELISA test kits usually mis-detected the elevated Aβ 42 Os, leading to incomplete analysis and underestimation of soluble Aβ 42 , resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ 42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ 42 Ms and Aβ 42 Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ 42 Ms or/and Aβ 42 Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment., (© 2021. The Author(s).)

In healthcare, new diagnostic tools that help in the diagnosis, prognosis, and monitoring of diseases rapidly and accurately are in high demand. For in-situ measurement of disease or infection biomarkers, point-of-care devices provide a dramatic speed advantage over conventional techniques, thus aiding clinicians in decision-making. During the last decade, paper-based analytical devices, combining paper substrates and electrochemical detection components, have emerged as important point-of-need diagnostic tools. This review highlights significant works on this topic over the last five years, from 2015 to 2019. The most relevant articles published in 2018 and 2019 are examined in detail, focusing on device fabrication techniques and materials applied to the production of paper fluidic and electrochemical cell architectures as well as on the final device assembly. Two main approaches were identified, that are, on one hand, those ones where the fabrication of the electrochemical cell is done on the paper substrate, where the fluidic structures are also defined, and, on the other hand, the fabrication of those ones where the electrochemical cell and liquid-driving paper component are defined on different substrates and then heterogeneously assembled. The main limitations of the current technologies are outlined and an outlook on the current technology status and future prospects is given., Competing Interests: The authors declare no conflict of interest.

Paper-based microfluidic analysis devices (μPADs) have attracted attention as a cost-effective platform for point-of-care testing (POCT), food safety, and environmental monitoring. Recently, three-dimensional (3D)-μPADs have been developed to improve the performance of μPADs. For accurate diagnosis of diseases, however, 3D-μPADs need to be developed to simultaneously detect multiple biomarkers. Here, we report a 3D-μPADs platform for the detection of multiple biomarkers that can be analyzed and diagnosed with a smartphone. The 3D-μPADs were fabricated using a 3D digital light processing printer and consisted of a sample reservoir (300 µL) connected to 24 detection zones (of 4 mm in diameter) through eight microchannels (of 2 mm in width). With the smartphone application, eight different biomarkers related to various diseases were detectable in concentrations ranging from normal to abnormal conditions: glucose (0-20 mmol/L), cholesterol (0-10 mmol/L), albumin (0-7 g/dL), alkaline phosphatase (0-800 U/L), creatinine (0-500 µmol/L), aspartate aminotransferase (0-800 U/L), alanine aminotransferase (0-1000 U/L), and urea nitrogen (0-7.2 mmol/L). These results suggest that 3D-µPADs can be used as a POCT platform for simultaneous detection of multiple biomarkers.

There is a need for large-scale, longitudinal studies to determine the mechanisms by which the gut microbiome and its interactions with the host affect human health and disease. Current methods for profiling the microbiome typically utilize next-generation sequencing applications that are expensive, slow, and complex. Here, we present a synthetic biology platform for affordable, on-demand, and simple analysis of microbiome samples using RNA toehold switch sensors in paper-based, cell-free reactions. We demonstrate species-specific detection of mRNAs from 10 different bacteria that affect human health and four clinically relevant host biomarkers. We develop a method to quantify mRNA using our toehold sensors and validate our platform on clinical stool samples by comparison to RT-qPCR. We further highlight the potential clinical utility of the platform by showing that it can be used to rapidly and inexpensively detect toxin mRNA in the diagnosis of Clostridium difficile infections.

The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Enzyme linked immunosorbent assay (ELISA) is one of the most widely used laboratory disease diagnosis methods. However, performing ELISA in low-resource settings is limited by long incubation time, large volumes of precious reagents, and well-equipped laboratories. Herein, we developed a simple, miniaturized paper/PMMA (poly(methyl methacrylate)) hybrid microfluidic microplate for low-cost, high throughput, and point-of-care (POC) infectious disease diagnosis. The novel use of porous paper in flow-through microwells facilitates rapid antibody/antigen immobilization and efficient washing, avoiding complicated surface modifications. The top reagent delivery channels can simply transfer reagents to multiple microwells thus avoiding repeated manual pipetting and costly robots. Results of colorimetric ELISA can be observed within an hour by the naked eye. Quantitative analysis was achieved by calculating the brightness of images scanned by an office scanner. Immunoglobulin G (IgG) and Hepatitis B surface Antigen (HBsAg) were quantitatively analyzed with good reliability in human serum samples. Without using any specialized equipment, the limits of detection of 1.6 ng/mL for IgG and 1.3 ng/mL for HBsAg were achieved, which were comparable to commercial ELISA kits using specialized equipment. We envisage that this simple POC hybrid microplate can have broad applications in various bioassays, especially in resource-limited settings.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

Purpose: Up to now, there is no generally accepted biomarker to indicate the clinical response of immunotherapy. This study mainly analyzed the correlation between eosinophil cationic protein-myeloperoxidase (ECP-MPO) test papers and other immunotherapy indices in subcutaneous immunotherapy of dust mites and to explore whether the test paper can be used as an auxiliary index to quickly evaluate the efficacy of immunotherapy. Patients and methods: This study included 53 participants who received subcutaneous immunotherapy at the allergy clinic of Renmin Hospital of Wuhan University and 28 control participants. Six visits were conducted during a prospective study over one year. The results of the ECP-MPO test paper, nasal secretion eosinophil smear and count, nasal secretion ECP concentration, and clinical symptom scores were collected during five follow-up visits after the start of subcutaneous immunotherapy. Th1/Th2/Th17 cytokines, chemokines, IgE, IgG4 against dust mite components, and ECP concentrations were detected in the serum of participants at baseline, six months, and one year after subcutaneous immunotherapy. Results: The ECP test paper is not only easy to operate, but also can effectively and quickly detect the concentrations of ECP in the nasal secretion and diagnose allergic rhinitis. Symptom score is an important index for evaluating clinical immune efficacy, during subcutaneous immunotherapy, the ECP test paper showed a positive correlation with the symptom score. Simultaneously, during immunotherapy, the changes in the chromogenic grading of the test paper were synchronized with the changes in inflammatory cytokines and eosinophilic chemokines in Th2 cells of serum dust mite IgE. The sIgG4 against dust mites weakly negatively correlated with the concentration of ECP in nasal secretions and the color classification of the ECP test paper. Conclusion: The ECP-MPO test paper has a certain correlation with subcutaneous immunotherapy markers of allergic rhinitis, indicating that the ECP test paper may become an auxiliary biomarker to replace other complex laboratory tests. [ABSTRACT FROM AUTHOR]

Background: There has been increasing interest in both suicide-specific diagnoses within the psychiatric nomenclature and related biomarkers. Because the Suicide Crisis Syndrome-an emotional crescendo of several interrelated symptoms-seems to be promising for the identification of individuals at risk of suicide, the aim of the present paper is to review the putative biological underpinnings of the Suicide Crisis Syndrome symptoms (entrapment, affective disturbance, loss of cognitive control, hyperarousal, social withdrawal)., Methods: A PubMed literature search was performed to identify studies reporting a link between each of the 5 Suicide Crisis Syndrome symptoms and biomarkers previously reported to be associated with suicidal outcomes., Results: Disturbances in the hypothalamic-pituitary-adrenal axis, with dysregulated corticotropin-releasing hormone and cortisol levels, may be linked to a sense of entrapment. Affective disturbance is likely mediated by alterations in dopaminergic circuits involved in reward and antireward systems as well as endogenous opioids. Loss of cognitive control is linked to altered neurocognitive function in the areas of executive function, attention, and decision-making. Hyperarousal is linked to autonomic dysregulation, which may be characterized by a reduction in both heart rate variability and electrodermal activity. Social withdrawal has been associated with oxytocin availability. There is also evidence that inflammatory processes may contribute to individual Suicide Crisis Syndrome symptoms., Conclusion: The Suicide Crisis Syndrome is a complex syndrome that is likely the consequence of distinct changes in interconnected neural, neuroendocrine, and autonomic systems. Available clinical and research data allow for development of empirically testable hypotheses and experimental paradigms to scrutinize the biological substrates of the Suicide Crisis Syndrome., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

The 2019 13 th Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA on 1-5 April 2019 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers, immunogenicity and gene therapy. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS, LBA cell-based/flow cytometry assays and qPCR approaches. This 2019 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2019 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on the 2018 FDA BMV guidance, 2019 ICH M10 BMV draft guideline and regulatory agencies' input on bioanalysis, biomarkers, immunogenicity and gene therapy. Part 1 (Innovation in small molecules and oligonucleotides and mass spectrometry method development strategies for large molecules bioanalysis) and Part 3 (New insights in biomarker assay validation, current and effective strategies for critical reagent management, flow cytometry validation in drug discovery and development and CLSI H62, interpretation of the 2019 FDA immunogenicity guidance and gene therapy bioanalytical challenges) are published in volume 10 of Bioanalysis , issues 22 and 24 (2019), respectively.

In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO 2 -Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO 2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO 2 -Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK-MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10-20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r 2 = 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The 2018 12 th Workshop on Recent Issues in Bioanalysis took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for PK, PD and ADA assays by hybrid LBA/LCMS and regulatory agencies' input. Part 1 (LCMS for small molecules, peptides, oligonucleotides and small molecule biomarkers) and Part 3 (LBA/cell-based assays: immunogenicity, biomarkers and PK assays) are published in volume 10 of Bioanalysis , issues 22 and 24 (2018), respectively.

The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings.

This systematic review, initiated by the European Cooperation in Science and Technology Action Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease (PARENCHIMA), focuses on potential clinical applications of magnetic resonance imaging in renal non-tumour disease using magnetic resonance relaxometry (MRR), specifically, the measurement of the independent quantitative magnetic resonance relaxation times T1 and T2 at 1.5 and 3Tesla (T), respectively. Healthy subjects show a distinguishable cortico-medullary differentiation (CMD) in T1 and a slight CMD in T2. Increased cortical T1 values, that is, reduced T1 CMD, were reported in acute allograft rejection (AAR) and diminished T1 CMD in chronic allograft rejection. However, ambiguous findings were reported and AAR could not be sufficiently differentiated from acute tubular necrosis and cyclosporine nephrotoxicity. Despite this, one recent quantitative study showed in renal transplants a direct correlation between fibrosis and T1 CMD. Additionally, various renal diseases, including renal transplants, showed a moderate to strong correlation between T1 CMD and renal function. Recent T2 studies observed increased values in renal transplants compared with healthy subjects and in early-stage autosomal dominant polycystic kidney disease (ADPKD), which could improve diagnosis and progression assessment compared with total kidney volume alone in early-stage ADPKD. Renal MRR is suggested to be sensitive to renal perfusion, ischaemia/oxygenation, oedema, fibrosis, hydration and comorbidities, which reduce specificity. Due to the lack of standardization in patient preparation, acquisition protocols and adequate patient selection, no widely accepted reference values are currently available. Therefore this review encourages efforts to optimize and standardize (multi-parametric) protocols to increase specificity and to tap the full potential of renal MRR in future research.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive method sensitive to local water motion in the tissue. As a tool to probe the microstructure, including the presence and potentially the degree of renal fibrosis, DWI has the potential to become an effective imaging biomarker. The aim of this review is to discuss the current status of renal DWI in diffuse renal diseases. DWI biomarkers can be classified in the following three main categories: (i) the apparent diffusion coefficient-an overall measure of water diffusion and microcirculation in the tissue; (ii) true diffusion, pseudodiffusion and flowing fraction-providing separate information on diffusion and perfusion or tubular flow; and (iii) fractional anisotropy-measuring the microstructural orientation. An overview of human studies applying renal DWI in diffuse pathologies is given, demonstrating not only the feasibility and intra-study reproducibility of DWI but also highlighting the need for standardization of methods, additional validation and qualification. The current and future role of renal DWI in clinical practice is reviewed, emphasizing its potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease, as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. As part of the international COST (European Cooperation in Science and Technology) action PARENCHIMA (Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease), aimed at eliminating the barriers to the clinical use of functional renal magnetic resonance imaging, this article provides practical recommendations for future design of clinical studies and the use of renal DWI in clinical practice.

Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action 'Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease' (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development.The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium.The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid ligand binding assay (LBA)/LCMS and LBA approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for biotherapeutics, biomarkers and immunogenicity assays using hybrid LBA/LCMS and regulatory agencies' inputs. Part 1 (LCMS for small molecules, peptides and small molecule biomarkers) and Part 3 (LBA: immunogenicity, biomarkers and pharmacokinetic assays) are published in Volume 9 of Bioanalysis, issues 22 and 24 (2017), respectively.

The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los Angeles/Universal City, California, on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule analysis involving LC-MS, hybrid ligand-binding assay (LBA)/LC-MS and LBA approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large-molecule bioanalysis, biomarkers and immunogenicity using LBA. Part 1 (LC-MS for small molecules, peptides and small molecule biomarkers) and Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) are published in volume 9 of Bioanalysis, issues 22 and 23 (2017), respectively.

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California from 3 April 2017 to 7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis, Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS and ligand-binding assay (LBA) approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for Small Molecules, Peptides and Small Molecule Biomarkers using LCMS. Part 2 (Biotherapeutics, Biomarkers and Immunogenicity Assays using Hybrid LBA/LCMS and Regulatory Agencies' Inputs) and Part 3 (LBA: Immunogenicity, Biomarkers and PK Assays) are published in volume 9 of Bioanalysis, issues 23 and 24 (2017), respectively.

Paper-based sensors have received increasing attention in the last decade, their use has spread to various application fields, such as clinical diagnostic, food safety, environmental monitoring, etc. Feature inherent to on-side detection is suitable to be used as point-of-care (POC) testing, including avoided sampling, sample preparation, and laborious procedure in the classical clinical lab, which is undoubtedly driving many developments of this lab-on-paper technology. The detection of biomarkers that are related to human health conditions has to play important role in the indication of the risk of diseases. In this review, the development of paper-based sensors for the detection of important biomarkers is presented. The also emphasis on recognition elements, such as chromophores/fluorophores, plasmonic nanoparticles, metal nanoclusters, etc., used to serve suitable selectivity and sensitivity. The performance of paper-based sensors using various techniques, including optical and electrochemical and other detection techniques are addressed. Furthermore, their limitations and prospects are discussed. The review also highlights cutting-edge technologies for further enhancement in the sensor performances for biomarkers detection.

The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of tuberculosis (TB) at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample matrix. For obtaining optimal sensitivity, we and others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples. A number of systems are paper-based often destined for resource limited settings. Our current work presents incorporation of one such sample pretreatment, proteinase K (ProK) immobilized on paper (IPK) and test its performance in comparison to standard proteinase K (SPK) treatment that involves addition and deactivation at high temperature prior to performing a capture ELISA. Herein, a simple and economical method was developed for using ProK immobilized strips to pretreat urine samples. Simplification and cost reduction of the proposed pretreatment strip were achieved by using Whatman no.1 paper and by minimizing the concentration of ProK (an expensive but necessary reagent) used to pretreat the clinical samples prior to ELISA. To test the applicability of IPK, capture ELISA was carried out on either LAM-spiked urine or the clinical samples after pretreatment with ProK at 400 μg/mL for 30 minutes at room temperature. The optimal conditions and stability of the IPK were tested and validation was performed on a set of 25 previously analyzed archived clinical urine samples with known TB and HIV status. The results of IPK and SPK treated samples were in agreement showing that the urine LAM test currently under development has the potential to reach adult and pediatric patients regardless of HIV status or site of infection, and to facilitate global TB control to improve assay performance and ultimately treatment outcomes., Competing Interests: The authors have declared that no competing interests exist.

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a weeklong event - A Full Immersion Week of Bioanalysis for PK, Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on PK, biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 3) discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Parts 1 (small molecule bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in the Bioanalysis journal, issues 22 and 23, respectively.

The 2016 10th Workshop on Recent Issues in Bioanalysis (10 th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 2) discusses the recommendations for Hybrid LBA/LCMS and regulatory inputs from major global health authorities. Parts 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) have been published in the Bioanalysis journal, issues 22 and 23, respectively.

Paper-based analytical devices have been widely used for biomedical, environmental and food-quality testing. This review focuses on paper-based tests for biomarkers and bacterial detection with a brief introduction about various fabrication techniques and designs, biological and nonbiological probes and detection methods. Paper is relatively cheap and available in abundance. Moreover, properties of paper such as it being disposable, easy to use and store, and that it is easy to transport and modify draw significant attention to it as a platform for the development of paper-based analytical devices. These traits make paper-based analytical devices a strong candidate in point-of-care devices for rapid and economical testing near the site of patients.

BackgroundChronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated.MethodsThe study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks.DiscussionThis study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables.Trial registrationClinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations that emerged from the extensive discussions held during the workshop, and is aimed at providing the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to advance scientific excellence, improve quality and deliver better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 2 covers the recommendations for hybrid LBA/LCMS and regulatory agencies' inputs. Part 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in volume 7 of Bioanalysis, issues 22 and 24, respectively.

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5 day, week-long event - A Full Immersion Bioanalytical Week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS and LBA approaches, including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 3 discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Part 1 (small molecule bioanalysis using LCMS) and Part 2 (hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in volume 7, issues 22 and 23 of Bioanalysis, respectively.

This study compared the use of sentinel species- and community-based field approaches for assessing the biological status of fish living in a river receiving pulp and paper mill effluents. Three approaches were compared. Two approaches used sentinel species. One of these involved an internal/external examination of the fish that leads to the calculation of a fish health assessment index (HAI) and the other involved biochemical measurements of hepatic mixed function oxidase (MFO) activity and plasma steroid levels. The third approach characterized the fish community structure according to an index of biotic integrity (IBI). The comparison focused on how the methods respond to the hypothesis that recent process modifications/effluent treatment changes, resulting in demonstrable improvements in effluent quality, have beneficial effects on fish. Neither of the approaches using sentinel fish indicated clear mill-related influences either before or after the process modifications/effluent treatment changes. There was no evidence of depressed plasma steroids and increased MFO activity in fish frequently associated with mill effluent exposure in previous studies. While the HAI was higher at stations downstream from two mills, this could not be linked to effluent exposure alone. In contrast, the study of community structure showed a substantial improvement in fish assemblages at all the mill sites.

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations that emerged from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to advance scientific excellence, improve quality and deliver better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 1 covers the recommendations for small molecule bioanalysis using LCMS. Part 2 (hybrid LBA/LCMS and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will also be published in volume 7 of Bioanalysis, issues 23 and 24, respectively.

Sepsis is an immune response to a microbial invasion that causes organ injury and dysfunction due to a systemic inflammatory response. Sepsis is a serious, life-threatening condition and a widely recognized global health challenge. Given its high death rate, it is critical to diagnose sepsis and start treatment as early as possible. There is an urgent need for a sensitive and rapid screening method for detecting sepsis. In this study, we investigated the use of MMP-9 as a biomarker for sepsis. A colorimetric paper-based biosensor was used for the detection of MMP-9 utilizing peptide-magnetic nanoparticle conjugates. The method is based on the cleavage of the MMP-9-specific peptide by the protease leading to the detaching of the magnetic beads from the sensor surface and changing of color. A fecal intraperitoneal (FIP) challenge was used to induce sepsis in mice, and an MMP-9 secretion was measured by taking blood and Bronchoalveolar Lavage (BAL) fluid samples at 1 h, 2 h, 4 h, and 20 h (early sepsis) post-challenge intervals. The results of the paper-based sensor for the detection of MMP-9 levels in blood samples and BAL samples were compared with ELISA and Western Blot. We found that both blood and BAL levels of MMP-9 increased immediately and could be detected as early as 1 h in FIP mice post-challenge. Our work adds evidence to the assertion that MMP-9 is a reliable biomarker for the detection of sepsis at early stages.

The prevalence of iron deficiency is high -even in the absence of anaemia- in patients with chronic heart failure (HF). Although iron deficiency is easily diagnosed with two biomarkers (serum ferritin and transferrin saturation), it is underdiagnosed in patients with HF. Iron is not only necessary for red blood cells, but also for cells in tissues with high-energy demands (heart, muscle, brain). Even before the onset of anaemia, HF patients with iron deficiency have decreased physical and cognitive performances and a poorer quality of life. Moreover, iron deficiency is a risk factor, independent of anaemia, of unfavourable outcome (death or heart transplantation) in patients with chronic HF. Several randomized controlled studies have shown improvement in exercise capacity, New York Heart Association functional class and quality of life after correction of iron deficiency. The results of these clinical trials, which are supported by European guidelines, suggest considering iron deficiency in HF as a possible therapeutic target., (Copyright © 2014. Published by Elsevier Masson SAS.)

With noncommunicable diseases (NCDs) now constituting the majority of global mortality, there is a growing need for low-cost, noninvasive methods to diagnose and treat this class of diseases, especially in resource-limited settings. Molecular biomarkers combined with low-cost point-of-care assays constitute a potential solution for diagnosing NCDs, but the dearth of naturally occurring, predictive markers limits this approach. Here, we describe the design of exogenous agents that serve as synthetic biomarkers for NCDs by producing urinary signals that can be quantified by a companion paper test. These synthetic biomarkers are composed of nanoparticles conjugated to ligand-encoded reporters via protease-sensitive peptide substrates. Upon delivery, the nanoparticles passively target diseased sites, such as solid tumors or blood clots, where up-regulated proteases cleave the peptide substrates and release reporters that are cleared into urine. The reporters are engineered for detection by sandwich immunoassays, and we demonstrate their quantification directly from unmodified urine; furthermore, capture antibody specificity allows the probes to be multiplexed in vivo and quantified simultaneously by ELISA or paper lateral flow assay (LFA). We tailor synthetic biomarkers specific to colorectal cancer, a representative solid tumor, and thrombosis, a common cardiovascular disorder, and demonstrate urinary detection of these diseases in mouse models by paper diagnostic. Together, the LFA and injectable synthetic biomarkers, which could be tailored for multiple diseases, form a generalized diagnostic platform for NCDs that can be applied in almost any setting without expensive equipment or trained medical personnel.

Background: The Taiwan Oncology Society (TOS) and the Taiwan Society of Pathology (TSP) have collaborated to present a joint position paper on the molecular tumor boards (MTBs) within the medical institutions of Taiwan. Materials and Methods: To raise awareness of MTBs among health-care professionals, policymakers, and the public, a total of 20 experts from TOS and TSP formulated a joint consensus statement through a voting process. Results: The joint statement proposes key recommendations: (1) MTB discussions encompass diverse molecular analyses including next-generation sequencing (NGS), RNA sequencing, whole-exon sequencing, and whole-genomic sequencing addressing relevant genomic changes, tumor mutation burden, microsatellite instability, and specific biomarkers for certain cancers. (2) MTB meetings should involve multidisciplinary participants who receive regular updates on NGS-related clinical trials. (3) Prioritize discussing cases with unique clinical needs, gene alterations lacking treatments, untreatable neoplasms, or oncogenes unresponsive to targeted therapies. (4) Base MTB discussions on comprehensive patient data, including genetics, pathology, timing of specimen collection, and NGS outcomes. (5) MTBs offer treatment recommendations: standard therapies, off-label use, clinical trials, genetic counseling, and multidisciplinary reviews. (6) MTB effectiveness can be gauged by member composition, case reviews, treatment suggestions, and patient outcomes. Encourage government incentives for MTB engagement. Conclusion: The primary aim of this initiative is to promote the advancement of precision oncology in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Harmful Alcohol use is frequent among opioid dependents patients undergoing agonist maintenance treatment. The objective assessment of harmful alcohol use can be done using laboratory measures of serum biomarkers. For community-based patients, there is often a requirement of an alternative method due to lack of onsite laboratory services. The aim of the study was to examine filter paper as a matrix to measure serum biomarkers of harmful alcohol use. Methods: The initial phase involved standardization of the filter-paper-based assay. Conditions were optimised for extraction and estimation of alcohol biomarkers (Aspartate Aminotransferase; AST, Alanine Aminotransferase; ALT, Gamma Glutamyl transferase; GGT and Carbohydrate Deficient Transferrin; CDT) from the filter paper. For clinical validation, serum samples were collected from community clinics. Biomarker levels obtained from both the methods were correlated using linear regression analysis. Limits of agreement between the two methods was estimated using the Intraclass Correlation Coefficient (ICC). Results: The extraction of enzymes (AST, ALT and GGT) from filter paper was carried out using the substrate buffer available with the reagent kit (Randox, UK). CDT was readily extracted from filter paper using deionised water. Serum biomarker levels measured from samples collected from community clinics correlated well with filter paper extracted levels (ICC 0.97-0.99). More than 90% of alcohol biomarker levels were recovered from the filter paper matrix using this method. Conclusion: Filter paper has the potential to be used as a matrix to objectively measure alcohol biomarkers among opioid-dependent patients from community settings lacking onsite laboratory facilities. [ABSTRACT FROM AUTHOR]

In a large proportion of individuals with fronto-temporal lobar degeneration (FTLD), the underlying pathology is associated with the misfolding and aggregation of the microtubule associated protein tau (FTLD-tau). With disease progression, widespread protein accumulation throughout cortical and subcortical brain regions may be responsible for neurodegeneration. One of the syndromes of FTLD is the behavioral variant of frontotemporal dementia (bvFTD), in which the underlying pathology is heterogenous, with half of the cases being related to FTLD-tau. Currently, there are no approved disease-modifying treatments for FTLD-tau, therefore representing a major unmet therapeutic need. These descriptive, preliminary findings of the phase 1 open-label trial provide data to support the potential of sodium selenate to halt the cognitive and behavioral decline, as well as to reduce tau levels in a small group of participants with bvFTD (N = 11). All participants were treated with sodium selenate over a period of 52 weeks. Cognition was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG, total scores), social cognition with the Revised Self-Monitoring Scale (RSMS, total scores), behavior with the Cambridge Behavioral Inventory (CBI), and carer burden with the Caregiver Buden Scale (CBS). Fluid biomarker measures include cerebrospinal fluid of total tau (t-tau), phosphorylated tau (p-tau181), NfL, p-tau181/t-tau, t-tau/Aβ1–42, and p-tau181/Aβ1–42 levels. After treatment at follow-up, cognition and behavior showed further negative change (based on a reliable change criterion cut-off of annual NUCOG decline) in the “progressors,” but not in the “non-progressors.” “Non-progressors” also showed elevated baseline CSF tau levels and no increase after treatment, indicating underlying tau pathology and a positive response to sodium selenate treatment. Significant changes in MRI were not observed. The findings provide useful information for future clinical trials to systematically assess the disease-modifying treatment effects of sodium selenate in randomized controlled designs for bvFTD and FTLD-tau pathologies.

In this study, a paper-based sensor was developed for the detection of hydrogen-peroxide-related biomarkers, with glucose oxidase catalyzing as an example. Potassium iodide can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine in the presence of hydrogen peroxide to colorize the paper-based biosensor detection area, which was imaged by a scanner, and the color intensity was analyzed by the Adobe Photoshop. Under the optimal conditions, the color intensity shows a good linear relationship with hydrogen peroxide and glucose concentrations in the ranges of 0.1–5.0 mM and 0.5–6.0 mM, respectively. The detection limit of hydrogen peroxide is 0.03 mM and the limit of quantification of glucose is 0.5 mM. Besides, the method was employed in measuring glucose concentration in fruit samples, and the spiked recoveries are in the range of 95.4–106.1%. This method is cost-effective, environmentally friendly, and easy to be operated, which is expected to realize the point-of-care testing of more hydrogen-peroxide-related biomarkers. [ABSTRACT FROM AUTHOR]