Currently, dental caries is the main reason of patient visits to dentists. A great deal of scientific work is dedicated to the study of enamel caries. The reason for this is the necessity for more detailed study of the pathogenesis of dental caries and other pathological processes occurring in tooth enamel. The application of modern high-technological methods of research has made it possible to study enamel structure in detail. Hard dental tissues are composed of organic and inorganic components and water. The organic substance consists of proteins, lipids, and carbohydrates. At different ages, caries intensity may vary. The carious process often develops during the first months after the tooth eruption but much less in adulthood and old age. These processes are mainly associated with the mechanisms of ionic exchange between the oral cavity and hard dental tissues. Different groups of teeth are differently affected by the carious process. Previous studies have revealed that age is an important factor influencing on the structure and chemical composition of hard dental tissues. Various recent works at the Department of Therapeutic Dentistry of Voronezh N.N. Burdenko State Medical Academy (VSMA) have studied not only the structural-morphological features of the enamel in children and adults but also the level of metabolic processes inside it. As a result of aging, teeth change both the enamel structure and the level of its ionic processes, but unfortunately, these changes have not been well characterized in teeth with conventional age-specific differences.

For both-the target group (hyposalivation) and positive control group (periodontitis)-FS phenotype was demonstrated to be more specific compared to the disease-free (negative control) group. Moreover, self-reports provided by interviewed adolescents of the target group frequently recorded remarkable discomfort related to "dry mouth" syndrome, acute and chronic otorhinolaryngological infections and even delayed wound healing. Further, interviewed adolescents do worry about the symptoms which might be indicative for potential diseases; they are also amazed that too little attention is currently paid to the issue by caregivers. In conclusion, FS questionnaire linked to the "dry mouth" syndrome is strongly recommended for application in primary healthcare. Consequently, targeted preventive measures can be triggered early in life. For example, traditional, complementary and alternative medicine demonstrates positive therapeutic effects in individuals suffering from xerostomia. For in-depth diagnostics, epi/genetic regulations involved into pathophysiologic mechanisms of hyposalivation in FS-affected individuals should be thoroughly investigated at molecular level. Identified biomarker panels might be of great clinical utility for predictive diagnostics and patient stratification that, further, would sufficiently improve personalised care to the patient.

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.

Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...

The article contains an overview of the literature on Mallory-Weiss syndrome. It analyzes numerous etiological factors, provides new insights into the pathogenesis of the disease, gives a description of a previously unknown dependence of discontinuous-hemorrhagic syndrome on the topographic and structural features of the cardioesophageal area of the digestive tract, and gives scientific credence to methods of prediction, prevention, and treatment of the syndrome with complex involvement of granular sorbents.