Voice perturbations under the stress overload in young individuals: phenotyping and suboptimal health as predictors for cascading pathologies

Abstract

Verbal communication is one of the most sophisticated human motor skills reflecting both—the mental and physical health of an individual. Voice parameters and quality changes are usually secondary towards functional and/or structural laryngological alterations under specific systemic processes, syndrome and pathologies. These include but are not restricted to dry mouth and Sicca syndromes, body dehydration, hormonal alterations linked to pubertal, menopausal, and andropausal status, respiratory disorders, gastrointestinal reflux, autoimmune diseases, endocrinologic disorders, underweight versus overweight and obesity, and diabetes mellitus. On the other hand, it is well-established that stress overload is a significant risk factor of cascading pathologies, including but not restricted to neurodegenerative and psychiatric disorders, diabetes mellitus, cardiovascular disease, stroke, and cancers. Our current study revealed voice perturbations under the stress overload as a potentially useful biomarker to identify individuals in suboptimal health conditions who might be strongly predisposed to associated pathologies. Contextually, extended surveys applied in the population might be useful to identify, for example, persons at high risk for respiratory complications under pandemic conditions such as COVID-19. Symptoms of dry mouth syndrome, disturbed microcirculation, altered sense regulation, shifted circadian rhythm, and low BMI were positively associated with voice perturbations under the stress overload. Their functional interrelationships and relevance for cascading associated pathologies are presented in the article. Automated analysis of voice recordings via artificial intelligence (AI) has a potential to derive digital biomarkers. Further, predictive machine learning models should be developed that allows for detecting a suboptimal health condition based on voice recordings, ideally in an automated manner using derived digital biomarkers. Follow-up stratification and monitoring of individuals in suboptimal health conditions are recommended using disease-specific cell-free nucleic acids (ccfDNA, ctDNA, mtDNA, miRNA) combined with metabolic patterns detected in body fluids. Application of the cost-effective targeted prevention within the phase of reversible health damage is recommended based on the individualised patient profiling.

Carotenoids in Cancer Metastasis—Status Quo and Outlook

“…The application of carotenoids in metastatic disease management of different origin is considered as a potentially effective mitigating measure, stratifying patients by individual diagnosis, dosing, and safety of medication [ 20 , 114 , 164 ]. At the level of primary prevention, innovative screening programs are essential to identify persons at high risk to develop particularly aggressive cancer sub/types who might be strongly predisposed to metastatic disease [ 164 , 165 , 166 , 167 , 168 , 169 ]. At the level of secondary prevention, cancer patients should undergo predictive diagnostics estimating individual metastatic potential.…”

Mitochondriopathies as a Clue to Systemic Disorders—Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine

“…However, a variety of conditions causing excessive ROS production, such as exposure to genotoxic environments, multi-factorial stress, suboptimal health conditions, and metabolic syndromes [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], may lead to unrepaired mitochondrial DNA (mtDNA) damage and concomitant functional defects in mitochondrial complexes I and III, associated with significantly increased uncontrolled formation of extremely aggressive ·O2- [ 3 ]. The arising imbalanced overproduction of ROS and consequent oxidative damage to mitochondrial structures impairs the ability of mitochondria to synthesize an appropriate amount of ATP [ 18 ] and, therefore, significantly reduces the energy resources of the cell needed to perform all the vital functions including highly energy-consuming DNA repair [ 35 ].…”

“…Conditions Multi-factorial stress conditions [ 26 , 27 ] Genotoxic environment [ 28 ] Suboptimal health conditions such as primary and secondary vasospasm leading to mitochondrial damage, due to systemic ischemic-reperfusion injury [ 26 , 31 ] Vasoconstriction and disease predisposition to Sicca syndrome, eye disorders, “young stroke” of unclear etiology, and aggressive cancer-subtypes [ 15 , 30 , 32 , 164 , 165 ] Inappropriate diet [ 31 ] Metabolic syndromes such as diabetes mellitus type 2, due to multi-factorial damage to mitochondria [ 33 ] and hyperhomocysteinemia, due to chronic oxidative stress [ 34 ] Chronic inflammation and predisposition to impaired healing, cancer, and neurodegeneration [ 166 , 167 ] Autoimmune disorders such as Sjögren’s syndrome with contributing inflammatory and vascular components [ 168 ] Acute infectious diseases such as COVID-19; viral infections provoke necrosis, which amplifies anti-viral immune responses, releasing damage-associated molecular patterns. Severely affected cells and tissues intrinsically secrete cell-free nucleic acids such as mtDNA.…”

“…Suboptimal health conditions such as primary and secondary vasospasm leading to mitochondrial damage, due to systemic ischemic-reperfusion injury [ 26 , 31 ]…”

“…Corresponding analytical tools Application of specialized surveys [ 26 , 29 , 30 ] Broad application and comprehensive analysis of liquid biopsy [ 7 , 9 , 10 ] Individualized patient profiling and innovative screening programs focused on young populations [ 11 , 12 , 167 ] Risk assessment, predictive, and companion diagnostics [ 10 ] Multi-omics, multi-parametric analysis, and machine learning [ 171 , 172 , 173 ] …”