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BackgroundStress during the early ERCP learning curve may interfere with acquisition of skills during training. The purpose of this study was to compare stress biomarkers in the saliva of trainees before and after familiarisation with ERCP exercises on a virtual simulator.MethodsAltogether 26 endoscopists under training, 14 women and 12 men, completed the three phases of this study: Phase 1. Three different ERCP procedures were performed on the simulator. Saliva for α-amylase (sAA), Chromogranin A (sCgA), and Cortisol (sC) were collected before (baseline), halfway through the exercise (ex.), and 10 min after completion of the exercise (comp.); Phase 2. A three-week familiarisation period where at least 30 different cases were performed on the virtual ERCP simulator; and Phase 3. Identical to Phase 1 where saliva samples were once again collected at baseline, during, and after the exercise. Percentage differences in biomarker levels between baseline and exercise (Diffex) and between baseline and completion (Diffcomp) during Phase 1 and Phase 3 were calculated for each stress marker.ResultsMean % changes, Diffex and Diffcomp, were significantly positive (p

Background. Respiratory symptoms of bronchial asthma (BA) comorbid with gastroesophageal reflux disease (GERD) may provoke duodenogastroesophageal reflux (DGER) via aggressive agents like pepsinogens and bilirubin.Objectives. A clinical and functional study of the saliva pepsinogen and bilirubin-associated BA-comorbid GERD for non-invasive DGER diagnosis.Methods. A total of 29 patients with an allergic BA phenotype, comorbid GERD and 50,2 ± 2,4 years mean age have been examined. Biochemical blood panel included bilirubin, C-reactive protein and allergen-specific IgE. Saliva bilirubin was estimated in colorimetry, and the pepsinogen-1, -2 content — in immunological tests. Grade A–D reflux oesophagitis (RO) in oesophagoscopy was assigned to erosive reflux disease, and grade N–M oesophageal mucosa (OM) lesions — to non-erosive reflux disease. External respiratory function (ERF) was assessed with forced expiratory volume (FEV1, L/s), forced vital capacity (FVC), Tiffeneau index (FEV1/FVC), pre- and post-berodual FEF1 and FVC dynamics.Results. The BA–GERD patients were markedly polymorbid. Cough and chest tightness associated with age, and the tight chest rate — with a higher body mass index and lower FEV1/FVC. The association between higher pepsinogen-I and lower FEV1/FVC–FVC in response to inhaled berodual, as well as between higher saliva bilirubin and lower FVC–FEV1 after berodual intake reflects a significant high-DGER effect on BA representation.Conclusion. In BA–GERD patients, saliva pepsinogen and bilirubin are biomarkers of both DGER and respiratory inflammation with bronchospasm.

Simulated endoscopic training can be challenging and stressful for the novice trainee. The absence of a reliable stress detection method during simulated endoscopic training makes estimating trainees' mental stress difficult to quantify. This study concomitantly measures the responses of four saliva stress biomarkers and compares them to the video score (VS) achieved by novice endoscopists in a reproducibly stressful simulation environment. Thirty-six male endoscopy naïve surgery residents were enrolled. After an orientation phase, a saliva specimen was collected for cortisol (sC), alpha-amylase (sAA), Chromogranin A (sCgA), and immunoglobulin A (sIgA) measurements (baseline phase, BL). Thereafter, the simulation exercise phase (E) started, practicing in the Fundamentals of Endoscopic Surgery Skills module (GI-Bronch Mentor). Immediately after, a second saliva sample for measuring the above-cited biomarkers was collected. The whole experiment was videotaped, and the VS was calculated. The percentage (E-BL)diff of each of the four saliva biomarkers was calculated and examined for correlation to VS. sCgAdiff showed the best correlation with VS, followed by sAAdiff. sCgA and sAA, are saliva stress biomarkers that are easy to collect non-invasively and showed the best correlation with novice endoscopist's performance in our simulation setting, and therefore, they could be used for monitoring stress. [ABSTRACT FROM AUTHOR]

Background: Stress during the early ERCP learning curve may interfere with acquisition of skills during training. The purpose of this study was to compare stress biomarkers in the saliva of trainees before and after familiarisation with ERCP exercises on a virtual simulator., Methods: Altogether 26 endoscopists under training, 14 women and 12 men, completed the three phases of this study: Phase 1. Three different ERCP procedures were performed on the simulator. Saliva for α-amylase (sAA), Chromogranin A (sCgA), and Cortisol (sC) were collected before (baseline), halfway through the exercise (ex.), and 10 min after completion of the exercise (comp.); Phase 2. A three-week familiarisation period where at least 30 different cases were performed on the virtual ERCP simulator; and Phase 3. Identical to Phase 1 where saliva samples were once again collected at baseline, during, and after the exercise. Percentage differences in biomarker levels between baseline and exercise (Diff ex ) and between baseline and completion (Diff comp ) during Phase 1 and Phase 3 were calculated for each stress marker., Results: Mean % changes, Diff ex and Diff comp , were significantly positive ( p  < 0.05) for all markers in both Phase 1 and Phase 3. Diff ex in Phase 1 was significantly greater than Diff ex in Phase 3 ( p  < 0.05) for sAA and sCgA. Diff comp for sAA in Phase 1 was significantly greater than Diff comp in Phase 3 ( p  < 0.05). No significant differences were found in sC concentration between Phases 1 and 3., Conclusion: This study shows that familiarisation with the ERCP simulator greatly reduced stress as measured by the three saliva stress biomarkers used with sAA being the best. It also suggests that familiarisation with an ERCP simulator might reduce stress in the clinical setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Georgiou, Boyanov, Thanasas, Sandblom, Linardoutsos and Enochsson.)

The objective of this review is to provide recent evidence for the oral–gut axis connection and to discuss gastrointestinal (GI) immune response, inflammatory bowel disease (IBD) pathogenesis, and potential salivary biomarkers for determining GI health. IBD affects an estimated 1.3% of the US adult population. While genetic predisposition and environment play a role, abnormal immune activity and microbiota dysbiosis within the gastrointestinal tract are also linked in IBD pathogenesis. It has been inferred that a reduced overall richness of bacterial species as well as colonization of opportunistic bacteria induce systemic inflammation in the GI tract. Currently, there is supporting evidence that both oral and gut microbiota may be related to the development of IBD. Despite this, there are currently no curative therapies for IBD, and diagnosis requires samples of blood, stool, and invasive diagnostic imaging techniques. Considering the relative ease of collection, emerging evidence of association with non-oral diseases may imply that saliva microbiome research may have the potential for gut diagnostic or prognostic value. This review demonstrates a link between saliva and intestinal profiles in IBD patients, suggesting that saliva sampling has the potential to serve as a non-invasive biomarker for gut diseases such as IBD in the oral–gut axis. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is the most rapidly growing cardiovascular condition with an estimated prevalence of >37.7 million individuals globally. HF is associated with increased mortality and morbidity and confers a substantial burden, in terms of cost and quality of life, for the individuals and the healthcare systems, highlighting thus the need for early and accurate diagnosis of HF. The accuracy of HF diagnosis, severity estimation, and prediction of adverse events has improved by the utilization of blood tests measuring biomarkers. The contribution of biomarkers for HF management is intensified by the fact that they can be measured in short time at the point-of-care. This is allowed by the development of portable analytical devices, commonly known as point-of-care testing (POCT) devices, which exploit the advancements in the area of microfluidics and nanotechnology. The aim of this review paper is to present a review of POCT devices used for the measurement of biomarkers facilitating decision making when managing HF patients. The devices are either commercially available or in the form of prototypes under development. Both blood and saliva samples are considered. The challenges concerning the implementation of POCT devices and the barriers for their adoption in clinical practice are discussed. [ABSTRACT FROM AUTHOR]

Abstract Head and neck squamous cell carcinoma (HNSCC) represents the most common type of head and neck cancer worldwide. However, despite advances in cancer care globally there has been little progress in HNSCC, with survival remaining static and slightly worse in laryngeal squamous cell carcinoma with 5 year survivals remaining at ∼50%. Conventional analysis of tissue through cytopathology or histopathology are the mainstay of diagnosis. Furthermore there are no useful biomarkers for disease diagnosis or surveillance. With recent technological advances, particularly in next generation sequencing, here we explore the application of tumor DNA for HNSCC diagnosis and surveillance, to improve surgical margin analysis and the potential use of molecular agents aiding in the imaging of HNSCC. [ABSTRACT FROM AUTHOR]

The objective of this review is to provide recent evidence for the oral–gut axis connection and to discuss gastrointestinal (GI) immune response, inflammatory bowel disease (IBD) pathogenesis, and potential salivary biomarkers for determining GI health. IBD affects an estimated 1.3% of the US adult population. While genetic predisposition and environment play a role, abnormal immune activity and microbiota dysbiosis within the gastrointestinal tract are also linked in IBD pathogenesis. It has been inferred that a reduced overall richness of bacterial species as well as colonization of opportunistic bacteria induce systemic inflammation in the GI tract. Currently, there is supporting evidence that both oral and gut microbiota may be related to the development of IBD. Despite this, there are currently no curative therapies for IBD, and diagnosis requires samples of blood, stool, and invasive diagnostic imaging techniques. Considering the relative ease of collection, emerging evidence of association with non-oral diseases may imply that saliva microbiome research may have the potential for gut diagnostic or prognostic value. This review demonstrates a link between saliva and intestinal profiles in IBD patients, suggesting that saliva sampling has the potential to serve as a non-invasive biomarker for gut diseases such as IBD in the oral–gut axis.

Synthetic cannabinoids (SCs) are consumed as legal alternative to cannabis and often allow passing drug-screening tests. Their rapid transience on the drug scene, combined with their mostly unknown metabolic profiles, creates a scenario with constantly moving analytical targets, making their monitoring and identification challenging. The development of fast screening strategies for SCs, not directly focused on their chemical structure, as an alternative to the commonly applied target acquisition methods, would be highly appreciated in forensic and public health laboratories. An innovative untargeted metabolomics approach, focused on herbal components commonly used for ‘spice’ products, was applied. Saliva samples of healthy volunteers were collected at pre-dose and after smoking herbal components and analysed by high-resolution mass spectrometry. The data obtained, combined with appropriate statistical analysis, allowed to highlight and elucidate two markers (scopoletin and N,N-bis(2-hydroxyethyl)dodecylamine), which ratio permitted to differentiate herbal smokers from non-smokers. The proposed strategy will allow discriminating potential positives, on the basis of the analysis of two markers identified in the herbal blends. This work is presented as a step forward in SC drug testing, promoting a smart first-line screening approach, which will allow reducing the number of samples to be further investigated by more sophisticated HRMS methods.The development of an alternative, generic screening methods of synthetic cannabinoids, not directly based on the chemical structure, in order to provide fast response on its potential consumption. [ABSTRACT FROM AUTHOR]

The analysis of salivary biomarkers has gained interest and is advantageous for simple, safe, and non-invasive testing in diagnosis as well as treatment. This chapter explores the importance of saliva biomarkers and summarizes recent advances in biosensor fabrication. The identification of diagnostic, prognostic and therapeutic markers in this matrix enables more rapid and frequent testing when combined with the use of biosensor technology. Challenges and future goals are highlighted and examined., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim Investigate short-term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states. Materials and Methods Overall, 175 subjects representing each of five biofilm-gingival interface ( BGI) periodontal groups were enrolled in a single-blind, randomized study. After stent-induced biofilm overgrowth for 21 days subjects received either a manual or a power toothbrush to use during a 4 weeks resolution phase. At baseline and during induction and resolution, standard clinical parameters were measured. Subclinical parameters included multikine analysis of 13 salivary biomarkers and 16s Human Oral Microbe Identification Microarray ( HOMIM) probe analysis of subgingival plaque samples. Results All groups exhibited significantly greater reductions in bleeding on probing ( BOP) ( p = 0.002), gingival index ( GI) ( p = 0.0007), pocket depth ( PD) ( p = 0.04) and plaque index ( p = 0.001) with power brushing compared to manual. When BGI groups were combined to form a shallow PD ( PD ≤ 3 mm) and a deep PD group ( PD > 4 mm) power brushing reduced BOP and GI in subjects with both pocket depths. Power brushing significantly reduced IL-1β levels at resolution while changes in bacterial levels showed non-significant trends between both brushing modalities. Conclusions Short-term changes in select clinical parameters and subclinical salivary biomarkers may be useful in assessing efficacy of power brushing interventions in a spectrum of periodontal disease states. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) , 45-52 The aim of this study was to examine whether triple depletion of salivary-α-amylase (sAA), albumin (Alb) and immunoglobulins G (IgGs) may improve the visualization capability of proteins in two-dimensional gel electrophoresis (2-DE) of oral fluids (OF). Oral fluids from healthy volunteers were subjected sequentially to sAA removing device followed by application to an Alb and IgG immunoaffinity column (triple depletion). The depleted OF samples were analyzed using SDS-PAGE followed by 2-DE and protein identification using ion-trap mass spectrometry (MS). This specific triple depletion technique unmasked spots never visualized before. A total of 36 new spots were observed after depletion (348 vs 312 before depletion). Moreover, 58 spots showed more than twofold increase intensity after depletion. In the 60-69 kDa area, the depletion procedure unmasked 14 proteins including HSP70, LTA4H, L-Plastin, Desmoplakin that are known to be involved in disease pathogenesis. The ability to selectively remove and elute the most abundant OF proteins visualized on the 2-DE represents an important step in the characterization of human OF. The better visualization and gel resolution achieved will improve quantification abilities in 2-DE and in tag-MS leading to better identification of disease-specific biomarkers. We further analyzed the eluted Alb and IgGs isoforms suggesting a new methodology venue for OF. [ABSTRACT FROM AUTHOR]

Summary: The prevalence, stability, and impact of blood contamination in children''s saliva on the measurement of three of the most commonly assayed hormones were examined. Participants were 363 children (47% boys; ages 6–13 years) from economically disadvantaged families who donated saliva samples on 2 days in the morning, midday, and late afternoon. Samples (n=2178) were later assayed for cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). To index the presence of blood (and its components) in saliva, samples were assayed for transferrin. Transferrin levels averaged 0.37mg/dl (SD=0.46, range 0.0–5.5, Mode=0), and were: (1) highly associated within individuals across hours and days, (2) positively correlated with age, (3) higher for boys than girls, (4) higher in PM than AM samples, and (5) the highest (>1.0mg/dl) levels were rarely observed in samples donated from the same individuals. Transferrin levels were associated with salivary DHEA and C, but less so for T. As expected, the relationships were positive, and explained only a small portion of the variance. Less than 1% of the statistical outliers (+2.5 SDs) in salivary hormone distributions had correspondingly high transferrin levels. We conclude that blood contamination in children''s saliva samples is rare, and its effects on the measurement of salivary hormones is small. Guidelines and recommendations are provided to steer investigators clear of this potential problem in special circumstances and populations. [Copyright &y& Elsevier]

Abstract: A micelle-mediated phase separation without added chelating agents to preconcentrate trace levels of lead in human saliva as a prior step to its determination by capillary electrophoresis has been developed. The enrichment step is based on the cloud point extraction of lead with the non-ionic surfactant PONPE 7.5 in the absence of chelating agent. The surfactant-rich phase was diluted with acetonitrile and the resultant solution was injected directly into the CE instrument. Factors affecting the combined methodology such as surfactant-rich phase diluting agent, buffer pH and concentration, applied voltage, sample preparation and presence of additives were studied in detail. A BGE of 20mM imidazole containing 30% acetonitrile, pH 6.20 was found to be optimal for the separation of lead from other saliva constituents. Indirect detection was performed at 205nm. The detection limit value of lead for the preconcentration of 8ml of saliva was 11.4μgl−1. The calibration graph using the preconcentration system was linear with a correlation coefficient of 0.997 at levels near the detection limits up to at least 400μgl−1. The reproducibility (R.S.D.) on the basis of migration time and peak area were better than 0.68 and 3.6%, respectively. The method was successfully applied to the determination of lead in human saliva. [Copyright &y& Elsevier]

Background: Alzheimer´s disease (AD) is the most widespread dementia in the world, followed by vascular dementia. Since AD is a heterogeneous disease that shows several varied phenotypes, it is not easy to make an accurate diagnosis, so it arises when the symptoms are clear and the disease is already at an advanced stage. Therefore, it is important to find out biomarkers for early AD diagnosis that facilitate treatment or slow down the disease. Classic biomarkers are obtained from cerebrospinal fluid and plasma, along with brain imaging by positron emission tomography. Attempts have been made to discover uncommon biomarkers from other body fluids, which are addressed in this update., Objective: This update aims to describe recent biomarkers from minimally invasive body fluids for the patients, such as saliva, urine, eye fluid or tears., Methods: Biomarkers were determined in patients versus controls by single tandem mass spectrometry and immunoassays. Metabolites were identified by nuclear magnetic resonance and microRNAs with genome-wide high-throughput real-time polymerase chain reaction-based platforms., Results: Biomarkers from urine, saliva, and eye fluid were described, including peptides/proteins, metabolites, and some microRNAs. The association with AD neuroinflammation and neurodegeneration was analyzed, highlighting the contribution of matrix metalloproteinases, the immune system and microglia, as well as the vascular system., Conclusion: Unusual biomarkers have been developed, which distinguish each stage and progression of the disease, and are suitable for the early AD diagnosis. An outstanding relationship of biomarkers with neuroinflammation and neurodegeneration was assessed, clearing up concerns about the etiopathogenesis of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Utilising biomarkers for COVID-19 diagnosis, prediction of treatment response and overall prognostication have been investigated recently. However, these ventures have only considered the use of blood-based molecular markers. Saliva is another biofluid that warrants being applied in similar fashion with major advantages that centres on its non-invasive and repeatable collection as well as cost-efficiency. To this end, this article presents a hypothesis for the sources of biomarkers useful clinically for COVID-19 disease outcome estimation and identify the likely implications of their detection in saliva. [ABSTRACT FROM AUTHOR]

The paper concentrates on the role of saliva in the early diagnosis of salivary gland tumor. Due to the still not fully understood etiology of head and neck cancer, the fundamental objective of this study is to find tumor markers of salivary gland tumor progression. This work demonstrates the feasibility of Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR) to track spectral variations between saliva samples derived from healthy volunteers and from salivary gland tumor (tumor mixus , TM) patients. Furthermore, a Real-Time Polymerase Chain Reaction (RT-PCR) has been used to detect a selected genes expression associated with neoplasm changes. The obtained results imply that spectral signals attributed to the amide I/II (secondary structure of protein), carbohydrates and inorganic phosphates oscillations are the most sensitive to alterations associated with the salivary gland cancer progression. Several spectroscopic biomarkers have been indicated as potential predictors of salivary gland tumor development. Additionally, the RT-PCR results reveal the increased level of Bcl-2 factor in salivary gland tumor patients' samples which may be related to inhibition of apoptosis process and increasing uncontrolled cell proliferation. Such combination of physico-chemical methods is a unique approach towards better understanding the tumor's etiology and early diagnosis problem. Based on the promising findings presented in this article, it could be concluded that saliva fluid has a great potential to be used as a first-line diagnostic tool in patients with suspicion of salivary gland tumor. Unlabelled Image • Spectroscopic biomarkers were indicated as predictors of salivary gland tumor. • Saliva has a great potential to be used as a first-line diagnostic tool. • ATR-FTIR was used for distinction between control and salivary gland tumor patients. • There are valid changes in secondary structure of proteins upon cancer development. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to validate label-free quantitative proteomics (LFQ) against antibody-based methods for quantifying established periodontal disease biomarkers in saliva., Experimental Design: In an experimental gingivitis model, healthy volunteers (n = 10) provide saliva at baseline (d0), during the induction (d7, d14, d21) and resolution (d35) of gingival inflammation (total n = 50). Biomarker levels are analyzed by LFQ and time-resolved immunofluorometric assay (IFMA) or enzyme-linked immunosorbent assay (ELISA). Molecular matrix metalloproteinase (MMP)-8 forms are assessed by Western blot (WB) analysis., Results: LFQ detects significantly (p < 0.05) elevated MMP-8 (d21vsd7, d35vsd7) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 (d35vsd7). Latent MMP-8 (70-80 kDa) is present (d0-d35), but not active MMP-8 (50-60 kDa). LFQ and immunoassay data significantly correlate for MMP-8 (r = 0.36), myeloperoxidase (r = 0.39), polymorphonuclear leukocyte elastase (r = 0.33), and TIMP-1 (r = -0.24)., Conclusion and Clinical Relevance: LFQ can quantify enzyme levels in saliva, however lacks the ability to measure enzymatic activity. WB analysis reveals that MMP-8 may not be activated during induction of gingival inflammation. Significant but weak correlations between IFMA or ELISA and LFQ suggest a limited capacity of available antibodies to reliably quantify salivary biomarkers for periodontal diseases. Novel "anti-peptide" antibodies designed by newer targeted mass spectrometry-based approaches can help to overcome these drawbacks., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The soluble urokinase plasminogen activator receptor (suPAR) has been detected in blood, plasma, serum, urine, ovarian cystic fluid, and cerebrospinal fluid. Elevated suPAR levels in plasma have been associated with negative outcomes in various diseases, such as bacteremia, sepsis, SIRS, cardiovascular disease, cancer, and tuberculosis. The primary aim of this study was to investigate whether suPAR can be detected in saliva from healthy individuals and thus, if saliva suPAR can be related to plasma suPAR, CRP, BMI, or gender. Blood and unstimulated whole saliva was collected from 20 healthy individuals (10 female and 10 male, median age of 28 years; range 21-41). CRP and suPAR were measured with ELISA in saliva and serum/plasma. suPAR was detected in all saliva samples in the 5.2-28.1 ng/mL range, with a median value of 17.1 ng/mL. Saliva suPAR was significantly higher (P < 0.001) but not correlated to plasma suPAR in healthy young adults with normal plasma suPAR levels. suPAR and CRP levels were correlated in blood but not in saliva. No correlation was found between BMI, age, or gender and suPAR in saliva.