Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine.

The Hippo pathway and its downstream effectors, the transcriptional co-activators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), regulate organ growth and cell plasticity during animal development and regeneration. Remarkably, experimental activation of YAP/TAZ in the mouse can promote regeneration in organs with poor or compromised regenerative capacity, such as the adult heart and the liver and intestine of old or diseased mice. However, therapeutic YAP/TAZ activation may cause serious side effects. Most notably, YAP/TAZ are hyperactivated in human cancers, and prolonged activation of YAP/TAZ triggers cancer development in mice. Thus, can the power of YAP/TAZ to promote regeneration be harnessed in a safe way? Here, we review the role of Hippo signalling in animal regeneration, examine the promises and risks of YAP/TAZ activation for regenerative medicine and discuss strategies to activate YAP/TAZ for regenerative therapy while minimizing adverse side effects.

Endogenous DNA 3' Blocks Are Vulnerabilities for BRCA1 and BRCA2 Deficiency and Are Reversed by the APE2 Nuclease.

The APEX2 gene encodes APE2, a nuclease related to APE1, the apurinic/apyrimidinic endonuclease acting in base excision repair. Loss of APE2 is lethal in cells with mutated BRCA1 or BRCA2, making APE2 a prime target for homologous recombination-defective cancers. However, because the function of APE2 in DNA repair is poorly understood, it is unclear why BRCA-deficient cells require APE2 for viability. Here we present the genetic interaction profiles of APE2, APE1, and TDP1 deficiency coupled to biochemical and structural dissection of APE2. We conclude that the main role of APE2 is to reverse blocked 3' DNA ends, problematic lesions that preclude DNA synthesis. Our work also suggests that TOP1 processing of genomic ribonucleotides is the main source of 3'-blocking lesions relevant to APEX2-BRCA1/2 synthetic lethality. The exquisite sensitivity of BRCA-deficient cells to 3' blocks indicates that they represent a tractable vulnerability in homologous recombination-deficient tumor cells.

CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia.

ABSTRACT: The interplay between T-cell states of differentiation, dysfunction, and treatment response in acute myeloid leukemia (AML) remains unclear. Here, we leveraged a multimodal approach encompassing high-dimensional flow cytometry and single-cell transcriptomics and found that early memory CD8+ T cells are associated with therapy response and exhibit a bifurcation into 2 distinct terminal end states. One state is enriched for markers of activation, whereas the other expresses natural killer (NK)-like and senescence markers. The skewed clonal differentiation trajectory toward CD8+ senescence was also a hallmark indicative of therapy resistance. We validated these findings by generating an AML CD8+ single-cell atlas integrating our data and other independent data sets. Finally, our analysis revealed that an imbalance between CD8+ early memory and senescent-like cells is linked to AML treatment refractoriness and poor survival. Our study provides crucial insights into the dynamics of CD8+ T-cell differentiation and advances our understanding of CD8+ T-cell dysfunction in AML.

RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health.

Defects in the repair of DNA interstrand crosslinks (ICLs) are associated with the genome instability syndrome Fanconi anemia (FA). Here we report that cells with mutations in RFWD3, an E3 ubiquitin ligase that interacts with and ubiquitylates replication protein A (RPA), show profound defects in ICL repair. An amino acid substitution in the WD40 repeats of RFWD3 (I639K) found in a new FA subtype abolishes interaction of RFWD3 with RPA, thereby preventing RFWD3 recruitment to sites of ICL-induced replication fork stalling. Moreover, single point mutations in the RPA32 subunit of RPA that abolish interaction with RFWD3 also inhibit ICL repair, demonstrating that RPA-mediated RFWD3 recruitment to stalled replication forks is important for ICL repair. We also report that unloading of RPA from sites of ICL induction is perturbed in RFWD3-deficient cells. These data reveal important roles for RFWD3 localization in protecting genome stability and preserving human health.

Unveiling the Interlayer Interaction in a 1H/1T TaS2 van der Waals Heterostructure.

This study delves into the intriguing properties of the 1H/1T-TaS2 van der Waals heterostructure, focusing on the transparency of the 1H layer to the charge density wave of the underlying 1T layer. Despite the sizable interlayer separation and metallic nature of the 1H layer, positive bias voltages result in a pronounced superposition of the 1T charge density wave structure on the 1H layer. The conventional explanation relying on tunneling effects proves insufficient. Through a comprehensive investigation combining low-temperature scanning tunneling microscopy, scanning tunneling spectroscopy, non-contact atomic force microscopy, and first-principles calculations, we propose an alternative interpretation. The transparency effect arises from a weak yet substantial electronic coupling between the 1H and 1T layers, challenging prior understanding of the system. Our results highlight the critical role played by interlayer electronic interactions in van der Waals heterostructures to determine the final ground states of the systems.

luxA Gene From Enhygromyxa salina Encodes a Functional Homodimeric Luciferase.

Several clades of luminescent bacteria are known currently. They all contain similar lux operons, which include the genes luxA and luxB encoding a heterodimeric luciferase. The aldehyde oxygenation reaction is presumed to be catalyzed primarily by the subunit LuxA, whereas LuxB is required for efficiency and stability of the complex. Recently, genomic analysis identified a subset of bacterial species with rearranged lux operons lacking luxB. Here, we show that the product of the luxA gene from the reduced luxACDE operon of Enhygromyxa salina is luminescent upon addition of aldehydes both in vivo in Escherichia coli and in vitro. Overall, EsLuxA is much less bright compared with luciferases from Aliivibrio fischeri (AfLuxAB) and Photorhabdus luminescens (PlLuxAB), and most active with medium-chain C4-C9 aldehydes. Crystal structure of EsLuxA determined at the resolution of 2.71 Å reveals a (ß/α)8 TIM-barrel fold, characteristic for other bacterial luciferases, and the protein preferentially forms a dimer in solution. The mobile loop residues 264-293, which form a ß-hairpin or a coil in Vibrio harveyi LuxA, form α-helices in EsLuxA. Phylogenetic analysis shows EsLuxA and related proteins may be bacterial protoluciferases that arose prior to duplication of the luxA gene and its speciation to luxA and luxB in the previously described luminescent bacteria. Our work paves the way for the development of new bacterial luciferases that have an advantage of being encoded by a single gene.

Biomechanical increase in cervical esophageal wall tension during peristalsis.

During pharyngeal phase of swallowing, circumferential tension of the cervical esophagus (CTE) increases caused by a biomechanical process of laryngeal elevation pulling the cervical esophagus orad. The esophagus contracts longitudinally during esophageal peristalsis, therefore, we hypothesized that CTE increases during esophageal peristalsis by a biomechanical process. We investigated this hypothesis using 28 decerebrate cats instrumented with electromyographic (EMG) electrodes on the pharynx and esophagus, and esophageal manometry. We recorded CTE, distal esophageal longitudinal tension (DET), and orad laryngeal tension (OLT) using strain gauges. Peristalsis was stimulated by injecting saline into esophagus or nasopharynx. We investigated the effects of transecting the pharyngo-esophageal nerve (PEN), hypoglossal nerve (HG), or administering (10 mg/kg iv) hexamethonium (HEX). We found that the durations of CTE and DET increased and OLT decreased simultaneously during the total extent of esophageal peristalsis. CTE duration was highly correlated with DET but not esophageal EMG or manometry. The peak magnitudes of the DET and CTE were highly correlated. After HEX administration, peristalsis in the distal esophagus did not occur, and the duration of the CTE response decreased. PEN transection blocked the occurrence of cricopharyngeal or cervical esophageal response during peristalsis but had no significant effect on the CTE response. HG transection had no significant effect on CTE. We conclude that there is a significant CTE increase, independent of laryngeal elevation or esophageal muscle contraction, which occurs during esophageal peristalsis. This response is a biomechanical process caused by esophageal shortening that occurs during esophageal longitudinal contraction of esophageal peristalsis.NEW & NOTEWORTHY Circumferential tension of cervical esophagus (CTE) increases during esophageal peristalsis. CTE response is correlated with distal longitudinal tension on cervical esophagus during esophageal peristalsis but not laryngeal elevation or esophageal muscle contraction. CTE response is not blocked by transection of motor innervation of laryngeal elevating muscles or proximal esophagus but is temporally reduced after hexamethonium administration. We conclude that the CTE response is a biomechanical effect caused by longitudinal esophageal contraction during esophageal peristalsis.

Probing the Phase Transition to a Coherent 2D Kondo Lattice.

Kondo lattices are systems with unusual electronic properties that stem from strong electron correlation, typically studied in intermetallic 3D compounds containing lanthanides or actinides. Lowering the dimensionality of the system enhances the role of electron correlations providing a new tuning knob for the search of novel properties in strongly correlated quantum matter. The realization of a 2D Kondo lattice by stacking a single-layer Mott insulator on a metallic surface is reported. The temperature of the system is steadily lowered and by using high-resolution scanning tunneling spectroscopy, the phase transition leading to the Kondo lattice is followed. Above 27 K the interaction between the Mott insulator and the metal is negligible and both keep their original electronic properties intact. Below 27 K the Kondo screening of the localized electrons in the Mott insulator begins and below 11 K the formation of a coherent quantum electronic state extended to the entire sample, i.e., the Kondo lattice, takes place. By means of density functional theory, the electronic properties of the system and its evolution with temperature are explained. The findings contribute to the exploration of unconventional states in 2D correlated materials.

Ligands with polyfluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities.

The interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand how nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI [(Z)-5-(3,5-difluoro-4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one] that reach out from the Spinach2 ligand binding pocket. Studies of the interaction of these compounds with the aptamers revealed that polyfluorophenyl-modified ligands initiate a slow change in aptamer affinity that takes an extended time (half-life of ∼40 min) to achieve. The change in affinity appears to involve an initial disruption of the entrance to the ligand binding pocket followed by a gradual transition to a more defined structure for which the most likely driving force is an interaction of the gateway adenine with a nearby 2'OH group. These results suggest that polyfluorophenyl modifications might increase the ability of small molecule drugs to disrupt local structure and promote RNA remodeling.

Heat accumulation and phase transition induction in a VO2 thin film by a femtosecond pulse-periodic radiation.

The kinetics of optical switching due to the insulator-metal phase transition in a VO2 thin film is studied experimentally at different laser pulse repetition frequencies (PRFs) in the NIR range and compared with temperature kinetics obtained through the thermal conductance calculations. Two switching processes have been found with characteristic times <2 ms and <15 ms depending on the PRF; the former is explained by the accumulation of metallic domains remaining after a single-pulse phase transition, and the latter is referred to the heat accumulation in the film. Consequently, the dynamics of the microscopic domains is leading in the initiation of phase transition under pulse-periodic conditions compared to the macroscopic heat transfer. The reverse transition at the radiation turn-off depends on the PRF with a time coefficient of 17.5 µs/kHz and is determined by the metallic domains' decay in the film. The results are important for understanding the nature of the insulator-metal transition in thin films of VO2 as well as using them in all-optical switches of pulse-periodic laser radiation.

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer.

BACKGROUND: As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8+ T cells and creating a more favorable tumor microenvironment for immunotherapy. METHODS: To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated. RESULTS: After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8+ T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors. CONCLUSIONS: Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.

External quality assessment performance in ten countries: an IFCC global laboratory quality project.

OBJECTIVES: This study aimed to assess the validity of external quality assessment (EQA) laboratory results across various cultural and environmental contexts and to identify potential improvement areas. METHODS: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a 2-year study (2022 and 2023) in which EQA materials, related software and online training was provided by a commercial vendor to 100 laboratories in ten IFCC member society countries. The results were analysed on a monthly basis by the TF-GLQ, to show the number of submissions per country, tests per lab, acceptability rates, random failures and to get a measure of which analytes performed poorly. RESULTS: The EQA material was dispatched on a quarterly basis. Some countries had problems with customs releasing the material in a timely manner, resulting in laboratories not receiving them on time leading to no submission. We report here the results for the second year of the survey. The number of examinations varied between laboratories, ranging from seven to 84 analytes. Of the ten countries surveyed, six averaged greater than 90 % acceptable results over the whole 12-months cycle, one had unacceptable results for two of the nine months they returned results and the other four were considered to not perform to an acceptable standard. CONCLUSIONS: All 100 participating laboratories indicated satisfaction with the EQA survey and related services, including on-site training, and report handling. However, specimen receiving issues, suggest benefits in dispatching materials for a full 12-month cycle. Significant discrepancies in EQA performance indicate that four countries require long-term assistance, training and guidance. To ensure reliable patient results, promoting EQA in certain countries is essential to achieve the required level of quality.

Improvement of Alginate Extraction from Brown Seaweed (Laminaria digitata L.) and Valorization of Its Remaining Ethanolic Fraction.

This study aimed to improve the conventional procedure of alginate isolation from the brown seaweed (Laminaria digitata L.) biomass and investigate the possibility of further valorization of the ethanolic fraction representing the byproduct after the degreasing and depigmentation of biomass. The acid treatment of biomass supported by ultrasound was modeled and optimized regarding the alginate yield using a response surface methodology based on the Box-Behnken design. A treatment time of 30 min, a liquid-to-solid ratio of 30 mL/g, and a treatment temperature of 47 °C were proposed as optimal conditions under which the alginate yield related to the mass of dry biomass was 30.9%. The use of ultrasonic radiation significantly reduced the time required for the acid treatment of biomass by about 4 to 24 times compared to other available conventional procedures. The isolated alginate had an M/G ratio of 1.08, which indicates a greater presence of M-blocks in its structure and the possibility of forming a soft and elastic hydrogel with its use. The chemical composition of the ethanolic fraction including total antioxidant content (293 mg gallic acid equivalent/g dry weight), total flavonoid content (14.9 mg rutin equivalent/g dry weight), contents of macroelements (the highest content of sodium, 106.59 mg/g dry weight), and microelement content (the highest content of boron, 198.84 mg/g dry weight) was determined, and the identification of bioactive compounds was carried out. The results of ultra high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis confirmed the presence of 48 compounds, of which 41 compounds were identified as sugar alcohol, phenolic compounds, and lipids. According to the 2,2-diphenyl-1-picrylhydrazyl assay, the radical scavenging activity of the ethanolic fraction (the half-maximal inhibitory concentration of 42.84 ± 0.81 µg/mL) indicated its strong activity, which was almost the same as in the case of the positive control, synthetic antioxidant butylhydroxytoluene (the half-maximal inhibitory concentration of 36.61 ± 0.79 µg/mL). Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus) were more sensitive to the ethanolic fraction compared to Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei). The obtained results indicated the possibility of the further use of the ethanolic fraction as a fertilizer for plant growth in different species and antifouling agents, applicable in aquaculture.

Simulation of ultrasonic scattering from scatterer size distributions using Field II.

Quantitative analysis of radio frequency (RF) signals obtained from ultrasound scanners can yield objective parameters that are gaining clinical relevance as imaging biomarkers. These include the backscatter coefficient (BSC) and the effective scatterer diameter (ESD). Biomarker validation is typically performed in phantoms which do not provide the flexibility of systematic variation of scattering properties. Computer simulations, such as those from the ultrasound simulator Field II, can allow more flexibility. However, Field II does not allow simulation of RF data from a distribution of scatterers with finite size. In this work, a simulation method is presented which builds upon previous work by including Faran theory models representative of distributions of scatterer size. These are systematically applied to RF data simulated in Field II. The method is validated by measuring the root mean square error of the estimated BSC and percent bias of the ESD and comparing to experimental results. The results indicate the method accurately simulates distributions of scatterer sizes and provides scattering similar to that seen in data from clinical scanners. Because Field II is widely used by the ultrasound community, this method can be adopted to aid in validation of quantitative ultrasound imaging biomarkers.

Surface Glycans of Microvesicles Derived from Endothelial Cells, as Probed Using Plant Lectins.

Glycans of MVs are proposed to be candidates for mediating targeting specificity or at least promoting it. In contrast to exosomes, glycomic studies of MVs are largely absent. We studied the glycoprofile of endothelial cell-derived MVs using 21 plant lectins, and the results show the dominance of oligolactosamines and their α2-6-sialylated forms as N-glycans and low levels of α2-3-sialylated glycans. The low levels of α2-3-sialosides could not be explained by the action of extracellular glycosidases. Additionally, the level of some Man-containing glycans was also decreased in MVs. Spatial masking as the causative relationship between these low level glycans (as glycosphingolipids) by integral proteins or proteoglycans (thus, their lack of interaction with lectins) seems unlikely. The results suggest that integral proteins do not pass randomly into MVs, but instead only some types, differing in terms of their specific glycosylation, are integrated into MVs.

Kallopterolides A-I, a New Subclass of seco-Diterpenes Isolated from the Southwestern Caribbean Sea Plume Antillogorgia kallos.

Kallopterolides A-I (1-9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1-9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.

Use of oxymetazoline hydrochloride ophthalmic solution, 0.1% for improved lid symmetry in Graves' disease.

PURPOSE: The purpose of this study is to evaluate the usage of oxymetazoline hydrochloride ophthalmic solution, 0.1% in the treatment of Graves' disease to improve lid symmetry. METHODS: Fourteen patients were identified with unilateral upper eyelid retraction, secondary to Graves' disease. A phenylephrine test was performed to evaluate whether treating the unaffected (non-retracted) side would result in improved symmetry using Hering's law. Patients were prescribed oxymetazoline hydrochloride ophthalmic solution, 0.1% to instill into the unaffected eye. Marginal reflex distance 1 (MRD1) measurements were taken pre- and post-treatment and patient satisfaction surveys were completed. RESULTS: The average pre-treatment MRD1 difference between the right eye (OD) and the left eye (OS) was 2.46 [range 1.50-4.00]. The average post-treatment MRD1 difference between OD and OS was 0.39 [range 0.00-1.00]. One hundred percent of patients were satisfied or very satisfied with the improvement in symmetry. CONCLUSIONS: Oxymetazoline hydrochloride ophthalmic solution, 0.1% is a potential method to improve symmetry in patients with Graves' disease and unilateral upper eyelid retraction via Hering's law, especially for non-surgical candidates or those who prefer non-surgical treatment. Our results indicate improved MRD1 differences between fellow eyes and patient satisfaction regarding the symmetry of the upper eyelids.

Motivational orientations of students towards internet dependent behavior and measures for its prevention.

OBJECTIVE: Aim: The aim is to study the motivation of students towards Internet dependent behavior and develop practical recommendations for improving a set of measures for its prevention. PATIENTS AND METHODS: Materials and Methods: The research involved 154 students of the National Academy of Internal Affairs. Research methods: analysis and generalization of literature sources, questionnaire, statistical methods. RESULTS: Results: The priority motives of students who manifest Internet dependence behavior were identif i ed. The motivational orientations of students determine their systematic stay in the virtual environment and include, first of all, compliance with modern world trends; accessibility of content; the need for recognition of personal results by other users; satisfaction with virtual communication with the social environment. CONCLUSION: Conclusions: The practical recommendations for improving a set of measures to counteract the spread of Internet dependence among students were developed. Overcoming Internet dependence involves influencing a person to change his or her motivational and value as well as communication spheres. Prevention of Internet dependence involves public health professionals conducting awareness-raising as well as psychological and correctional work with the most vulnerable categories of people.

Modern educational needs of specialists in the public health system.

OBJECTIVE: Aim: Studying the opinion of public health system workers (emlpoyees) regarding existing educational problems and needs in the context of continuous professional development. PATIENTS AND METHODS: Materials and Methods: Bibliosemantic, medical-statistical, sociological methods are used in the study. The research program provided for conducting sociological surveys of public health specialists in different regions of the country regarding the establishment of priority training topics for public health specialists; preferred methods of learning; barriers to access to education, etc. The scientific base of the research the regional centers for disease control and prevention have become. Statistical processing and mathematical analysis of materials was carried out using methods of statistical analysis. RESULTS: Results: The research has found that the priority topics of training for public health specialists are issues of epidemiology (which were indicated as very important by 67.7±3.7 and as important by 22.0±3.2 per 100 respondents); emergency and disaster management (67.7±3.7 and 31.1±3.6 per 100 respondents), quality and safety (53.0±3.9 and 38.4±3.8), practices based on on evidence (42.1±3.9 and 45.7±3.9) eHealth and digitalization (40.2±3.8 and 38.4±3.8), statistics (38.4±3.8 and 51 ,2±3.9), research methodology (32.9±3.7 and 51.2±3.9) and research ethics (12.8±2.6 and 67.7±3.7, respectively). Webinars (62.2±3.8 per 100 respondents) and online training (60.4±3.8), classroom (42.1±3.9) and hybrid (40.2±3.8) were identified as preferred forms. teaching. The obstacles to the continuous professional development of public health specialists are a lack of time and a lack of finances, a lack of information about desired training programs, their regulations, insufficient support from management, military aggression and the problems caused by it, etc. CONCLUSION: Conclusions: The priority topics of training for public health specialists, preferred methods of training and barriers to access to training determined in the course of the study are the basis for improving the organization of continuous professional development of employees of public health centers.

Self-assessment of somatic and mental health by instructor-officers under the influence of negative factors of professional activities.

OBJECTIVE: Aim: To investigate the impact of negative factors of professional activities in the context of the COVID-19 pandemic and martial law in Ukraine on the somatic and mental health of instructor-officers with different teaching experiences. PATIENTS AND METHODS: Materials and Methods: The research involved 131 instructor-officers with different teaching experiences. Three groups of instructor-officers were formed: Group 1 - instructors with up to 10 years of teaching experience (n = 30), Group 2 - instructors with 10 to 20 years of experience (n = 47), Group 3 - instructors with more than 20 years of experience (n = 54). The self-assessment of somatic and mental health was carried out using a questionnaire developed by the authors. RESULTS: Results: The negative impact of the factors of professional activities in the context of the COVID-19 pandemic and martial law in Ukraine on the somatic and mental health of instructor-officers was established. More than 50 % of the instructors rated their health as satisfactory, and more than 20 % as poor. The overwhelming majority of instructors reported a slight (over 40 %) and significant (over 30 %) deterioration in both somatic and mental health. Health problems over the past year have interfered with the performance of professional duties for more than 80 % of instructor-officers. CONCLUSION: Conclusions: The systematic impact of negative factors can lead to some psychosomatic disorders and diseases in instructor-officers and a decrease in the quality of their teaching activities. This necessitates the search for ways to restore the somatic and mental health of instructor-officers.