Patterns of volatile organic compounds in excrements of preterm neonates.

BACKGROUND: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples. METHODS: We performed a feasibility study to investigate whether ambient air-independent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH). RESULTS: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p < 0.05. CONCLUSIONS: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates.

Advances in the Etiology, Detection, and Clinical Management of Seborrheic Keratoses.

Seborrheic keratoses (SKs) are ubiquitous, generally benign skin tumors that exhibit high clinical variability. While age is a known risk factor, the precise roles of UV exposure and immune abnormalities are currently unclear. The underlying mechanisms of this benign disorder are paradoxically driven by oncogenic mutations and may have profound implications for our understanding of the malignant state. Advances in molecular pathogenesis suggest that inhibition of Akt and APP, as well as existing treatments for skin cancer, may have therapeutic potential in SK. Dermoscopic criteria have also become increasingly important to the accurate detection of SK, and other noninvasive diagnostic methods, such as reflectance confocal microscopy and optical coherence tomography, are rapidly developing. Given their ability to mimic malignant tumors, SK cases are often used to train artificial intelligence-based algorithms in the computerized detection of skin disease. These technologies are becoming increasingly accurate and have the potential to significantly augment clinical practice. Current treatment options for SK cause discomfort and can lead to adverse post-treatment effects, especially in skin of color. In light of the discontinuation of ESKATA in late 2019, promising alternatives, such as nitric-zinc and trichloroacetic acid topicals, should be further developed. There is also a need for larger, head-to-head trials of emerging laser therapies to ensure that future treatment standards address diverse patient needs.

Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma: a step towards individualized medicine in glioblastoma.

OBJECTIVE: Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle-based liquid biopsy targeting nonneoplastic extracellular vesicles. METHODS: The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance. RESULTS: Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM. CONCLUSIONS: Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon's arsenal in the near future for the treatment and management of GBM patients.

Optical coherence tomography for patch test grading: A prospective study on its use for noninvasive diagnosis of allergic contact dermatitis.

BACKGROUND: The diagnosis of allergic contact dermatitis should be confirmed by skin patch tests. Distinguishing between irritant and allergic reactions is sometimes difficult. OBJECTIVES: To analyse the in vivo morphological changes in patch test reactions compared to healthy skin, and to detect subclinical changes in doubtful reactions using optical coherence tomography (OCT). To develop an OCT-based algorithm to support patch-test grading. METHODS: One hundred twenty-nine skin patch-test areas were scanned with OCT to evaluate the following features: architectural and vascular morphology, epidermal thickness, optical attenuation coefficient (AC), and blood flow at 0.1, 0.2, and 0.35 mm depth. RESULTS: Most common OCT features of acute contact allergic reactions in patch tests were spongiosis with microvesicles (94.8%), macrovesicles (60.3%), and coalescing vesicles (46.6%), the latter useful in differentiating acute allergic from irritant dermatitis (P-value < .05). Objective quantitative parameters correlated well with the severity grade: epidermal thickness due to spongiosis, AC (P-value < .05) and blood flow at 0.2 and 0.35 mm (P-value < .01). CONCLUSIONS: OCT as a noninvasive diagnostic tool, established for skin cancer diagnosis, is useful for evaluating contact allergic patch-test reactions. Not only morphological but also objective features such as blood flow and AC correlate with the reaction severity. Further studies are needed to explore the differences in irritant and allergic contact dermatitis.

[New optical examination procedures for the diagnosis of skin diseases]. / Neue optische Untersuchungsverfahren für die Diagnostik von Hautkrankheiten.

BACKGROUND: Since the establishment of dermoscopy as a routine examination procedure in dermatology, the spectrum of noninvasive, optical devices has further expanded. In difficult-to-diagnose clinical cases, these systems may support dermatologists to arrive at a correct diagnosis without the need for a surgical biopsy. OBJECTIVE: To give an overview about technical background, indications and diagnostic performance regarding four new optical procedures: reflectance confocal microscopy, in vivo multiphoton tomography, dermatofluoroscopy, and systems based on image analysis by artificial intelligence (AI). MATERIALS AND METHODS: This article is based on a selective review of the literature, as well as the authors' personal experience from clinical studies relevant for market approval of the devices. RESULTS: In contrast to standard histopathological slides with vertical cross sections, reflectance confocal microscopy and in vivo multiphoton tomography allow for "optical biopsies" with horizontal cross sections. Dermatofluoroscopy and AI-based image analyzers provide a numerical score, which helps to correctly classify a skin lesion. The presented new optical procedures may be applied for the diagnosis of skin cancer as well as inflammatory skin diseases. CONCLUSION: The presented optical procedures provide valuable additional information that supports dermatologists in making the correct diagnosis. However, a surgical biopsy followed by dermatohistopathological examination remains the diagnostic gold standard in dermatology.

Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide. Routine norovirus diagnosis requires stool collection. The goal of this study was to develop and validate a noninvasive method to diagnose norovirus to complement stool diagnostics and to facilitate studies on transmission. METHODS: A multiplex immunoassay to measure salivary immunoglobulin G (IgG) responses to 5 common norovirus genotypes (GI.1, GII.2, GII.4, GII.6, and GII.17) was developed. The assay was validated using acute and convalescent saliva samples collected from Peruvian children <5 years of age with polymerase chain reaction (PCR)-diagnosed norovirus infections (n = 175) and controls (n = 32). The assay sensitivity and specificity were calculated to determine infection status based on fold rise of salivary norovirus genotype-specific IgG using norovirus genotype from stool as reference. RESULTS: The salivary assay detected recent norovirus infections and correctly assigned the infecting genotype. Sensitivity was 71% and specificity was 96% across the evaluated genotypes compared to PCR-diagnosed norovirus infection. CONCLUSIONS: This saliva-based assay will be a useful tool to monitor norovirus transmission in high-risk settings such as daycare centers or hospitals. Cross-reactivity is limited between the tested genotypes, which represent the most commonly circulating genotypes.

Patient-specific requirements and clinical validation of MRI-based pressure mapping: A two-center study in patients with aortic coarctation.

BACKGROUND: Invasive peak-to-peak pressure gradients are the current clinical reference standard for assessing aortic coarctation. To obtain them, patients need to undergo arterial heart catheterization. Unless an intervention is performed, the procedure remains purely diagnostic, while the concomitant risks remain. PURPOSE: To validate MRI-based pressure mapping against pressure drop derived from heart catheterization and to define minimal clinical requirements. STUDY TYPE: Prospective clinical validation study. POPULATION: Twenty-seven coarctation patients with an indicated heart catheterization were enrolled at two clinical centers. MRI SEQUENCES: 1.5T including 4D velocity-encoded MRI and 3D anatomical imaging of the aorta. ASSESSMENT: Pressure drop across the stenosis was calculated by pressure mapping based on the pressure Poisson equation. Calculated pressure drops were compared with catheter measured data. Spatial and temporal resolution were analyzed using in silico phantom-based data as well as in vivo measurements. STATISTICS: Pressure drop was compared to peak-to-peak measurements. A two-sample paired mean equivalence test was used. RESULTS: In patients without imaging artifacts and a required spatial resolution ≥5 voxel/diameter, significant equivalence of pressure mapping compared to heart catheterization was found (17.5 ± 6.49 vs. 16.6 ± 6.53 mmHg, P < 0.001). DATA CONCLUSION: Pressure mapping provides equivalent accuracy to pressure drop obtained from heart catheterization in patients 1) without previous stenting and 2) with sufficient spatial image resolution (at least 5 voxels/diameter). In these patients the method can reliably be performed prior to the actual procedure, and thus allows safe noninvasive treatment planning based on MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:81-89.

Applicability of extracellular vesicles in clinical studies.

BACKGROUND: Extracellular vesicles (EVs) are submicron cellular fragments that mediate intercellular communication. EVs have in the last decade attracted major interest as biomarkers or platforms for biomarkers of health and disease. To better understand the reasons why despite great expectations and considerable effort, EV-based methods have not yet been introduced into clinical practice, we present a systematic analysis of published results of clinical studies. MATERIALS AND METHODS: Clinical studies on populations of body fluid samples, published from 2010 to including 2015, applying centrifugation of fluid human samples with centrifuge accelerations up to about 25 000 g and flow cytometry for detection of EVs were analysed with respect to statistical significance (p), statistical power (P), clinical significance (CS), defined as the difference between the means divided by the sum of standard deviations, and size of the populations (Nmin ), defined as the number of samples in the smaller group. RESULTS: Final analysis included 65 publications with 716 comparisons reporting 308 (43%) statistically significant differences (P < 0·05), 242 (34%) had statistical power P > 0·8 and 88 (12%) had clinical importance CS > 1·96. None of comparison with CS > 1·96 included populations in which the smaller group consisted of 50 or more samples. CONCLUSIONS: To fulfil claimed expectations for EV-based methods as promising diagnostic tools, more evidence on EV-based mechanisms of diseases should be gathered. Also, the methods of EV harvesting and assessment should be improved to yield better repeatability and thus allow clinical studies with larger number of samples.

Noninvasive in vivo monitoring of tissue-specific global gene expression in humans.

Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA and to monitor changes in tissue development and health. As one application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the analysis of mRNA, we observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron-specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer's disease and showed that disease specific neural transcripts are present at increased levels in the blood of affected individuals. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.

Salivary cysteine levels as a potential biochemical indicator of oral cancer risk in tobacco consumers.

Aim: Oral cancer is the leading cause of mortality, with a survival rate of less than 5 years, and is predominantly influenced by tobacco mutagens. Invasive diagnostic methods hinder early detection of oral cancer biomarkers. The present study performed salivary biochemical analysis for early oral cancer screening in tobacco consumers.Materials & methods: Three study groups included healthy controls (n = 25), tobacco users (n = 25) and oral cancer patients (n = 25). Salivary total protein, amylase, TNF-α and amino acid levels were evaluated using enzymatic tests, Enzyme linked Immunosorbent Assay (ELISA) and High-Performance Liquid Chromatography (HPLC).Results: Compared with healthy controls, salivary total protein and TNF-α levels were significantly (p = 0.04) higher in oral cancer patients. Salivary amylase levels were significantly lower in tobacco smokers (p = 0.02) and higher in oral cancer patients (p = 0.01). Interestingly, the amino acid cysteine concentration was significantly higher (p = 0.02) in tobacco consumers (62.5 ± 10) than in healthy controls (116.1 ± 28).Conclusion: In high-risk populations, such as tobacco users, salivary biochemical analysis can serve as a promising noninvasive diagnostic method for early oral cancer screening. As a salivary biomarker, the amino acid cysteine exhibits potential as a means of detecting the progression of oral cancer in individuals who consume tobacco.

[Box: see text].

[Diagnostics of acute compartment syndrome : Current gold standard and the state of science of noninvasive assessment methods]. / Diagnostik des akuten Kompartmentsyndroms : Aktueller Goldstandard und Stand der Wissenschaft nichtinvasiver Messmethoden.

Acute compartment syndrome (ACS) is defined by a disorder of the microcirculation due to a persistent pathological pressure increase within a muscle compartment. The ischemia of the tissue leads to an initially reversible functional impairment and finally irreversible damage of the musculature, nerves and other structures. Based on the understanding of the pathophysiology, the current diagnostic concepts and treatment using the so-called dermatofasciotomy of the affected muscle compartments can be derived. In addition to the suspicion of a possible ACS based on the medical history of the patient, the findings of the clinical examination are decisive. This review article gives a summary of all the essential aspects of the diagnostics. In clinically uncertain cases and for monitoring, an objectification of the findings using instrument-based techniques is increasingly required. Nowadays, invasive needle pressure measurement is available; however, due to limited reliability, specificity and sensitivity, these measurements only represent an aid to decision guidance supporting or advising against the indications for dermatofasciotomy. The increasing demands on making a certain diagnosis and justification of a surgical intervention from a legal point of view, substantiate the numerous scientific efforts to develop noninvasive instrument-based diagnostics. These methods are based either on detection of increasing intracompartmental pressure or decreasing perfusion pressure and microcirculation. The various measurement principles are summarized in a lucid form.

Spicy Recipe for At-Home Diagnostics: Smart Salivary Sensors for Point-of-Care Diagnosis of Jaundice.

Even though significant advances have been made, there is still a lack of reliable sensors capable of noninvasively monitoring bilirubin and diagnosing jaundice as the most common neonatal disease, particularly at the point-of-care (POC) where blood sampling from infants is accompanied by serious challenges and concerns. Herein, for the first time, using an easy-to-fabricate/use assay, we demonstrate the capability of curcumin embedded within paper for noninvasive optical monitoring of bilirubin in saliva. The highly selective sensing of the developed sensor toward bilirubin is attributed to bilirubin photoisomerization under blue light exposure, which can selectively restore the bilirubin-induced quenched fluorescence of curcumin. We also fabricated an IoT-enabled hand-held optoelectronic reader to measure and quantify the fluorescence and color signals of our sensor. Clinical analysis on the saliva of 18 jaundiced infants by using our developed smart salivary sensor proved that it is amenable to be widely exploited in POC applications for bilirubin monitoring as there are good correlations between its results with those of reference methods in saliva and blood. Meeting all WHO's REASSURED criteria by our developed sensor makes it a highly promising sensor for smart noninvasive diagnosis and therapeutic monitoring of jaundice, hepatitis, and other bilirubin-induced neurologic diseases at the POC.

Microbiota and glioma: a new perspective from association to clinical translation.

Gliomas pose a significant challenge in oncology due to their malignant nature, aggressive growth, frequent recurrence, and complications posed by the blood-brain barrier. Emerging research has revealed the critical role of gut microbiota in influencing health and disease, indicating its possible impact on glioma pathogenesis and treatment responsiveness. This review focused on existing evidence and hypotheses on the relationship between microbiota and glioma from progression to invasion. By discussing possible mechanisms through which microbiota may affect glioma biology, this paper offers new avenues for targeted therapies and precision medicine in oncology.

Hyperspectral imaging for non-invasive blood oxygen saturation assessment.

Hyperspectral Imaging (HSI) seamlessly integrates imaging and spectroscopy, capturing both spatial and spectral data concurrently. With widespread applications in medical diagnostics, HSI serves as a noninvasive tool for gaining insights into tissue characteristics. The distinctive spectral profiles of biological tissues set HSI apart from traditional microscopy in enabling in vivo tissue analysis. Despite its potential, existing HSI techniques face challenges such as alignment issues, low light throughput, and tissue heating due to intense illumination. This study introduces an innovative HSI system featuring active sequential bandpass illumination seamlessly integrated into conventional optical instruments. The primary focus is on analyzing oxyhemoglobin and deoxyhemoglobin saturation in animal tissue samples using multivariate linear regression. This approach holds promise for enhancing noninvasive medical diagnostics. A key feature of the system, active bandpass illumination, effectively prevents tissue overheating, thereby bolstering its suitability for medical applications.

A breath-based in vitro diagnostic assay for the detection of lower respiratory tract infections.

An accurate diagnosis is critical to reducing mortality in people with lower respiratory tract infections (LRTIs). Current microbiological culture is time-consuming, and nucleic acid amplification-based molecular technologies cannot distinguish between colonization and infection. Previously, we described developing a sampling system for effectively capturing biomolecules from human breath. We identified a new class of proteoform markers of protease activation, termed proteolytic products of infection, for detecting LRTIs in people with mechanical ventilation. Here, we further developed an in vitro assay by designing a specific substrate sensor for human neutrophil elastase (HNE) to detect LRTIs in breath samples. In the proof-of-concept study, we then applied this in vitro assay to breath samples collected from intubated patients and healthy volunteers. The findings revealed that the LRTI group demonstrated a significant mean differential, showing a 9.8-fold elevation in measured HNE activity compared with the non-LRTI group and a 9.2-fold compared with healthy volunteers. The in vitro assay's diagnostic potential was assessed by constructing a receiver operating characteristic curve, resulting in an area under the curve of 0.987. Using an optimal threshold for HNE at 0.2 pM, the sensitivity was determined to be 1.0 and the specificity to be 0.867. Further correlation analysis revealed a strong positive relationship between the measured HNE activity and the protein concentration in the breath samples. Our results demonstrate that this breath-based in vitro assay provides high diagnostic performance for LRTIs, suggesting that the technology may be useful in the near term for the accurate diagnosis of LRTIs.

Ammonia detection: A pathway towards potential point-of-care diagnostics.

Invasive methods such as blood collection and biopsy are commonly used for testing liver and kidney function, which are painful, time-consuming, require trained personnel, and may not be easily accessible to people for their routine checkup. Early diagnosis of liver and kidney diseases can prevent severe symptoms and ensure better management of these patients. Emerging approaches such as breath and sweat analysis have shown potential as non-invasive methods for disease diagnosis. Among the many markers, ammonia is often used as a biomarker for the monitoring of liver and kidney functions. In this review we provide an insight into the production and expulsion of ammonia gas in the human body, the different diseases that could potentially use ammonia as biomarker and analytical devices such as chemiresistive gas sensors for non-invasive monitoring of this gas. The review also provides an understanding into the different materials, doping agents and substrates used to develop such multifunctional sensors. Finally, the current challenges and the possible future trends have been discussed.

Elevated homocysteine is negatively correlated with plasma cystathionine ß-synthase activity in givosiran-treated patients.

Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine ß-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran-treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B6, a cofactor for CBS, in four patients during the trial, plasma CBS activity was found to increase, mirroring a corresponding decrease in homocysteine levels. These results support the hypothesis that elevated homocysteine levels following givosiran treatment result from a reduction of CBS activity and that vitamin B6 supplementation lowers homocysteine levels by increasing CBS activity.

Exploring salivary exosomes as early predictors of oral cancer in susceptible tobacco consumers: noninvasive diagnostic and prognostic applications.

BACKGROUND: Salivary exosome analysis provides a noninvasive and comprehensive approach with potential applications in oral cancer diagnosis and prognosis. The early detection of oral cancer has remained a critical concern in enhancing the quality of life, especially for individuals who consume tobacco and are at greater risk of developing the disease. The current study investigates the potential of salivary exosomes in screening smokers for early signs and transformations of oral cancer. METHODS: Morphological characterization of salivary exosomes among three study groups (non-smokers as control, smokers as high-risk tobacco consumers, and Oral cancer) (n = 120) was carried out through dynamic light scattering, and nanoparticle tracking analysis. For molecular characterization, EXOCET and Fourier transform infrared spectroscopy methods were utilized. The expression of the exosomal surface protein CD63 was evaluated using Western blotting. RESULTS: Salivary exosomes exhibit noticeable differences in size between control group and tobacco consumers. The differentiation extended beyond exosome size and included variations in concentration and bio-molecular composition, as determined by FTIR screening. Tobacco consumers and oral cancer groups showed significantly larger and more concentrated exosomes compared to the healthy group. CONCLUSION: Our study provides strong evidence that the properties of salivary exosomes can serve as reliable noninvasive biomarkers for distinguishing tobacco consumers from non-smokers and oral cancer patients. Our results underscore the potential of exosome-based diagnostics in early oral cancer detection for high-risk individuals. The larger size and higher concentration of exosomes in tobacco consumers indicate early changes in cell secretions associated with the transformation from healthy to abnormal cells.

Correlation of serum biochemical parameters and saliva pH in healthy individuals.

Saliva has the potential to work alongside needles in standard medical diagnosis. Yet the number of studies aimed at deciphering the biochemical communication between saliva and the rest of the body's systems is still very limited. The aim of this study is to investigate the interfluid interaction between saliva and serum by determining the correlation between saliva pH and serum biochemical parameters under mild conditions. Ultimately, using saliva may provide a stress-free diagnostic tool, but more ambitiously, the pH of saliva could present a genuine cost-effective screening tool that may immensely benefit areas with limited access to health care and diagnostic labs. Saliva and blood samples were collected from 43 randomly selected children (7-12 years), living in Jeddah, free from obesity and chronic or systemic body and mouth diseases. A complete serum biochemical analysis was performed, and the salivary pH of all samples was measured immediately at the time of collection. The correlations between saliva pH and serum biochemical parameters were investigated using Univariate and multiple linear regression models. Our results showed that pH has a weak significant positive correlation with total protein and a negative weak significant correlation with urea. Weak correlations suggest the existence of more serum factors to be investigated for their effect on the pH using a stepwise multiple linear regression. The multiple linear models' calculated saliva pH values were close to the measured values, demonstrating its possible capacity to predict saliva pH using serum parameters. The regression model's successful prediction of saliva pH using serum biochemicals reflects the significant correlations between the body fluids' parameters and invites more research to elucidate these relationships.

Sampling volume assessment for wearable multimodal optical diagnostic device.

The process and results of numerical Monte Carlo simulation of optical radiation propagation in laser Doppler flowmetry (LDF) and fluorescence spectroscopy (FS) channels of a wearable diagnostic multimodal device are described in this paper. To achieve the goal, a multilayer skin model with different parameters of blood and melanin content and different distances between sources and radiation receivers was designed. The changes in the sampling (diagnostic) volume depending on the anatomical features of the biological tissues, as well as on the technical parameters of the device were shown. Depending on the scattering media optical properties and the source-detector configuration of the device, the diagnostic volume can range from 2 to 7 mm3 . The obtained results allow the formation of specialized medical and technical requirements for wearable multimodal devices implementing LDF and FS channels.