Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies—all exerted system’s enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a “sick eye in a sick body” makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles.

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

Superficial temperature distribution patterns before and after physical activity in school children are indicative for personalized exercise coaching and disease prevention

Background Thermoregulation is highly individual and predictive for potentially cascading pathologies. Altered and deficient thermoregulation is considered an important diagnostic indicator which can be of great clinical utility for specialized screening programs and individualized prediction and prevention of severe pathologies triggered early in life. Working hypothesis Individual thermoregulation can be objectively assessed by thermovision camera before and after exercises in school children stratified by age and gender that may be of great clinical utility for personalized training early in life in the framework of 3P medicine. Study design In this study, 60 female and male primary school children were exposed to physical exercises in the form of 45-min general fitness training. The subjects under examination were stratified by age: group 1 (7-year-olds), group 2 (9-year-olds), and group 3 (12-year-olds). Superficial body temperature patterns were measured by means of thermovision camera before and immediately after exercises, as well as after the 15-min recovery time. Temperature patterns were analyzed in 12 areas of the body front and back, covering trunk and upper and lower limbs. Results The obtained results revealed an individual and age-depended difference in response of the body to exercises. The first measurement prior to exercise (measurement 1) revealed no statistically significant differences in the mean surface temperature of all analyzed areas between 7- and 9-year-old children. Further, 7- and 9-year-old children did not differ significantly in the mean temperature recorded in the trunk compared to the 12-year-old children. However, in 12-year-old children, statistically significant higher values of the mean temperature of the upper and lower limbs, were observed compared to the group of 7-year-olds and significantly higher values of the mean temperature of the lower limbs compared to the group of 9-year-olds. Immediately after exercises (measurement 2), a statistically significant decrease in the temperature was noted in all groups and in all areas of the body. The greatest temperature change was observed in 12-year-olds, while the least one was measured in the youngest subjects. The statistically significant relation between the average trunk temperature of 7-year-old and 12-year-old children was observed: lower values of the mean temperature of the front and back of the trunk were noted in the group of 12-year-old children compared to the group of 7-year-olds. A significantly lower average temperature of the back of the trunk compared to the youngest group was also recorded in 9-year-old children. The study performed after the 15-min recovery time (measurement 3) showed an increase in the average temperature of all analyzed areas. In all subjects, the mean temperature recorded in measurement 3 did not differ significantly from the initial ones (measurement 1, prior to exercises). Only the mean temperature of the trunk back of 12-year-old children was significantly lower after the rest period compared to the initial examination. In all groups, the temperatures after exercises followed by a 15-min recovery returned to the initial ones, except of the trunk backs of 12-year-old children, where the temperature was lower than before exercises. Conclusions and expert recommendations in the framework of 3PM Thermovision analysis is an effective tool to assess individual thermoregulation and to stratify school children for personalized exercise coaching. Body exercise-based disease prevention early in life is effective when tailored to the person: multi-parametric guidance for prescribing exercises individually is needed. Contextually, proposed individualized training approach should be adapted to the age-dependent particularities and individual thermoregulation.