The Conjugates of Indolo[2,3-b]quinoline as Anti-Pancreatic Cancer Agents: Design, Synthesis, Molecular Docking and Biological Evaluations.

New amide conjugates of hydroxycinnamic acids (HCAs) and the known antineoplastic 5,11-dimethyl-5H-indolo[2,3-b]quinoline (DiMIQ), an analog of the natural alkaloid neocryptolepine, were synthesized and tested in vitro for anticancer activity. The compound 9-[((2-hydroxy)cinnamoyl)amino]-5,11-dimethyl-5H-indolo[2,3-b]quinoline (2), which contains the ortho-coumaric acid fragment, demonstrated dose-dependent effectiveness against both normal BxPC-3 and metastatic AsPC-1 pancreatic cancer cells. The IC50 values for AsPC-1 and BxPC-3 were 336.5 nM and 347.5 nM, respectively, with a selectivity index of approximately 5 for both pancreatic cancer cells compared to normal dermal fibroblasts. Conjugate 2 did not exhibit any hemolytic activity against human erythrocytes at the tested concentration. Computational studies were performed to predict the pharmacokinetic profile and potential mechanism of action of the synthesized conjugates. These studies focused on the ADME properties of the conjugates and their interactions with DNA, as well as DNA-topoisomerase alpha and beta complexes. All of the conjugates studied showed approximately one order of magnitude stronger binding to DNA compared to the reference DiMIQ, and approximately two orders of magnitude stronger binding to the topoisomerase II-DNA complex compared to DiMIQ. Conjugate 2 was predicted to have the strongest binding to the enzyme-DNA complex, with a Ki value of 2.8 nM.

Synthesis, Biological Activity, ADME and Molecular Docking Studies of Novel Ursolic Acid Derivatives as Potent Anticancer Agents.

A series of new ursolic acid (UA) derivatives substituted with various amino acids (AAs) or dipeptides (DP) at the C-3 position of the steroid skeleton was designed and synthesized. The compounds were obtained by the esterification of UA with the corresponding AAs. The cytotoxic activity of the synthesized conjugates was determined using the hormone-dependent breast cancer cell line MCF-7 and the triple-negative breast cancer cell line MDA. Three derivatives (l-seryloxy-, l-prolyloxy- and l-alanyl-l-isoleucyloxy-) showed micromolar IC50 values and reduced the concentrations of matrix metalloproteinases 2 and 9. Further studies revealed that for two compounds (l-seryloxy- and l-alanyl-l-isoleucyloxy-), a possible mechanism of their antiproliferative action is the activation of caspase-7 and the proapoptotic Bax protein in the apoptotic pathway. The third compound (l-prolyloxy- derivative) showed a different mechanism of action as it induced autophagy as measured by an increase in the concentrations of three autophagy markers: LC3A, LC3B, and beclin-1. This derivative also showed statistically significant inhibition of the proinflammatory cytokines TNF-α and IL-6. Finally, for all synthesized compounds, we computationally predicted their ADME properties as well as performed molecular docking to the estrogen receptor to assess their potential for further development as anticancer agents.

Unexpected Reaction Products of Uracil and Its Methyl Derivatives with Acetic Anhydride and Methylene Chloride.

New acetyl derivatives of uracil, 6-methyluracil, and thymine were obtained in the course of an unconventional synthesis in methylene chloride. It was shown that products with the acetyloxymethyl fragment are formed according to a mechanism different from that for products with the acetyloxyethyl group. In particular, for uracil it was proven that the reaction with Ac2O, TEA, and CH2Cl2 leads to 1-acetyloxymethyluracil, where the N1 substituent is composed of the -CH2- fragment that originated from CH2Cl2 and the 1-acetyloxy moiety from Ac2O. The reaction of uracil with Ac2O, TEA, CH2Cl2, and DMAP leads to an acetyloxyethyl derivative in which the -CH2-CH2- fragment originates from TEA and the 1-acetyloxy moiety from Ac2O. A possible mechanism for the formation of new compounds was suggested and supported by the density functional theory/B3LYP quantum mechanical calculations. New compounds (39 in total, including seven deuterated) were fully characterized by nuclear magnetic resonance and high-resolution mass spectrometry techniques.

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application.

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (1), 5,11-dimethyl-5H-indolo[2,3-b]quinolin (2), capecitabine (3), diosgenin (4), tigogenin (5), flumethasone (6), fluticasone propionate (7), ursolic acid methyl ester (8), and ß-sitosterol (9) was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (1), and the derivatization of diosgenin (4), tigogenin (5), and capecitabine (3) resulted in obtaining different compounds from those designed. Nevertheless, in all above cases we were able to obtain thiol-containing derivatives of selected biological active compounds. Moreover, a modelling study for the two-step thiolation of genistein and some of its derivatives was accomplished using the density functional theory (B3LP). A hypothesis on a possible reason for the unsuccessful deprotection of the thiolated genistein is also presented based on the semiempirical (PM7) calculations. The developed methodology gives access to new sulphur derivatives, which might find a potential therapeutic benefit.

A diversity of alkylation/acylation products of uracil and its derivatives: synthesis and a structural study.

tert-Butyl dicarbonate (Boc2O) and ethyl iodide (EtI) reactions with uracil (U), thymine (T) and 6-methyluracil (6-MU) were performed following routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives. Parallel quantum mechanical DFT calculations supported the experimental findings.

Synthesis and Antioxidant Activity of Caffeic Acid Derivatives.

A series of caffeic acid derivatives were synthesized via a modified Wittig reaction which is a very important tool in organic chemistry for the construction of unsaturated carbon⁻carbon bonds. All reactions were performed in water medium at 90 °C. The aqueous Wittig reaction worked best when one unprotected hydroxyl group was present in the phenyl ring. The olefinations in the aqueous conditions were also conducted with good yields in the presence of two unprotected hydroxyl groups. When the number of the hydroxyl groups was increased to three, the reaction yields were worse, and the derivatives 12, 13, and 18 were obtained with 74%, 37%, and 70% yields, respectively. Nevertheless, the Wittig reaction using water as the essential medium is an elegant one-pot synthesis and a greener method, which can be a safe alternative for implementation in organic chemistry. The obtained compounds were tested for their antioxidant activity, and 12, 13, and 18 showed the highest activities. Moreover, all synthesized compounds displayed no cytotoxicity, and can therefore be used in the pharmaceutical or cosmetic industry.

An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study.

An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N,N'-di-Boc-N''-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed. Compound 1 revealed the highest activity against A549 lung adenocarcinoma and MCF7 breast cancer cell lines. Thus, 1 was evaluated for the in vivo anticancer activity against 4T1 mammary gland carcinoma and KLN205 murine lung carcinoma in mouse models. The anticancer effect was observed in the KLN205 model with a 37% tumor growth inhibition at the 20 mg/kg dose. This anticancer activity of 1 was comparable to that of cyclophosphamide which inhibited murine lung tumor growth in the range of 27-43% at the dose of 100 mg/kg. The biochemistry research after 1 admission, including measurements of blood parameters like alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and urea and creatinine, were also performed.

Emotional processes in patients undergoing coronary artery bypass graft surgeries with extracorporeal circulation in view of selected indicators of the inflammatory condition.

BACKGROUND: The aim of this study was to describe positive and negative emotions in patients undergoing coronary artery bypass graft (CABG) surgeries with extracorporeal circulation and the correlations between emotions and basic indicators of the inflammatory condition: C-reactive protein (CRP) concentration, body temperature, and leukocyte count. MATERIAL/METHODS: Standardized tools were used to select 52 patients (aged 47-63 years, 6 women--11.5% and 46 men--88.5%) without dementia or depression. The Positive and Negative Affect Schedule (PANAS) was used to examine positive affect (PA) and negative affect (NA) and the State-Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level. The patients underwent CABG surgery according to a common anesthesia protocol and for 5 consecutive days they were observed in the ward, where selected indicators of the inflammatory condition were monitored. RESULTS: A detailed description of the results of examinations of emotions was presented. The patients with low PA-trait level, high NA-trait level, and high anxiety-trait level (STAI X2) exhibited statistically significantly higher body temperatures than the other patients in the postoperative period. The patients with high NA-trait and anxiety-state levels (STAI X1) had statistically significantly lower CRP levels in the postoperative period than the patients with low NA-trait and anxiety-state levels (STAI X1). CONCLUSIONS: Patients undergoing CABG operations express both positive and negative affects. The changes in the inflammatory markers are expressed mostly by CRP concentration. There exist relationships between the result of tests assessing emotions and the markers of the inflammatory condition.

New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium.

The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.

Determination of organic volatile impurities in nepafenac by GC method.

The methods for controlling volatile impurities, including reagent and starting material, in Nepafenac active pharmaceutical ingredient, are reported. The proposed methods were developed using gas chromatography (GC) and gas chromatography with headspace injection (GC-HS) and validated according to the requirements of the ICH (International Conference of Harmonization) validation guidelines Q2R1 and the guideline for residual solvents Q3C.

[Determinants of personality and risky road behaviors at work in drivers of medical transport vehicles in the Wielkopolska (Greater Poland) voivodeship]. / Determinanty osobowosciowe a drogowe zachowania ryzykowne w pracy kierowców pojazdów uprzywilejowanych transportu medycznego w województwie wielkopolskim.

BACKGROUND: Personality determinants are an important predicator of road behaviors in drivers. The main objective of the study was to determine the relationship between personality determinants (neuroticism, extraversion, level of anxiety - features) and distinguishable risky behaviors of drivers of medical transport vehicles. MATERIAL AND METHODS: The study covered 106 male drivers from the Wielkopolskie Voivodeship, working in health care, having a license to drive emergency vehicles. To achieve the research objectives a questionnaire was developed and applied. It concerned risky road behaviors among drivers of medical transport. The personality suitability was determined using the questionnaire methods on self-assessment: Polish versions of Eysenck Personality Questionnaire - Revised (EPQ-R) and the State-Trait Anxiety Inventory (STAI) questionnaire. RESULTS: It was shown that drivers with introverted characteristics declare driving vehicles of reduced technical efficiency more often than extroverts. The level of the anxiety as a trait A-characteristic affects the display of distracting behaviors, making decisions about driving a vehicle that is inefficient, driving in a bad psychophysical condition, as well as maintaining too small distance from the preceding vehicle. The higher the intensity of anxiety characteristics, the higher the intensity of given behaviors. CONCLUSIONS: Based on the study results, it can be assumed that there is a relationship between determinants of personality and the display of risky behaviors of drivers of medical transport vehicles. Thus it can be concluded that the level of extraversion and anxiety as a trait are the differentiating characteristics of respondents.

The conjugates of 5'-deoxy-5-fluorocytidine and hydroxycinnamic acids - synthesis, anti-pancreatic cancer activity and molecular docking studies.

New amide conjugates 1-6 of hydroxycinnamic acids (HCA) and 5'-deoxy-5-fluorocytidine (5-dFCR), the prodrug of 5-fluorouracil (5-FU), were synthesized and tested in vitro against pancreatic cancer lines (PDAC). The compounds showed slightly higher efficacy against primary BxPC-3 cells (IC50 values of 14-45 µM) than against metastatic AsPC-1 (IC50 values of 37-133 µM), and similar to that of 5-FU for both PDAC lines. Compound 1, which has a para-(acetyloxy)coumaroyl substituent, was found to be the most potent (IC50 = 14 µM) with a selectivity index of approximately 7 to normal dermal fibroblasts (IC50 = 96 µM). The potential pharmacological profiles were discussed on the basis of the ADME data. Docking to the carboxylesterase CES2 showed that the synthesized compounds have the ability to bind via hydrogen bonding between a specific acetate group of the sugar moiety and Ser228, which belongs to the catalytic triad that causes hydrolysis. Docking to albumin, a major transport protein in the circulatory system, revealed a strong interaction of the conjugates at the binding site which is native to warfarin and responsible for its transport in the body.

Lazarus Phenomenon or the Return from the Afterlife-What We Know about Auto Resuscitation.

Autoresuscitation is a phenomenon of the heart during which it can resume its spontaneous activity and generate circulation. It was described for the first time by K. Linko in 1982 as a recovery after discontinued cardiopulmonary resuscitation (CPR). J.G. Bray named the recovery from death the Lazarus phenomenon in 1993. It is based on a biblical story of Jesus' resurrection of Lazarus four days after confirmation of his death. Up to the end of 2022, 76 cases (coming from 27 countries) of spontaneous recovery after death were reported; among them, 10 occurred in children. The youngest patient was 9 months old, and the oldest was 97 years old. The longest resuscitation lasted 90 min, but the shortest was 6 min. Cardiac arrest occurred in and out of the hospital. The majority of the patients suffered from many diseases. In most cases of the Lazarus phenomenon, the observed rhythms at cardiac arrest were non-shockable (Asystole, PEA). Survival time after death ranged from minutes to hours, days, and even months. Six patients with the Lazarus phenomenon reached full recovery without neurological impairment. Some of the causes leading to autoresuscitation presented here are hyperventilation and alkalosis, auto-PEEP, delayed drug action, hypothermia, intoxication, metabolic disorders (hyperkalemia), and unobserved minimal vital signs. To avoid Lazarus Syndrome, it is recommended that the patient be monitored for 10 min after discontinuing CPR. Knowledge about this phenomenon should be disseminated in the medical community in order to improve the reporting of such cases. The probability of autoresuscitation among older people is possible.

d-Glucose- and d-mannose-based antimetabolites. Part 4: Facile synthesis of mono- and di-acetates of 2-deoxy-d-glucose prodrugs as potentially useful antimetabolites.

2-Deoxy-d-glucose (2-DG), a compound known to interfere with d-glucose and d-mannose metabolism, has been tested as a potential anticancer and antiviral agent. Preclinical and clinical studies focused on 2-DG have highlighted several limitations related to 2-DG drug-like properties, such as poor pharmacokinetic properties. To overcome this problem, we proposed design and synthesis of novel 2-DG prodrugs that subsequently could be tested using a variety of biochemical and molecular methods. We narrowed here our focus to esters of 2-DG as potential prodrugs based on the hypothesis that ubiquitous esterases will regenerate 2-DG, leading to increased circulation time of drug and adequate organ and tumor penetration. Testing this hypothesis in vitro and, especially, in vivo requires significant amounts of respective pure mono- and previously unknown di-acetylated water-soluble derivatives of 2-DG. Development of their efficient and practical method of synthesis was imperative. We describe novel facile and scalable syntheses of seven selectively acetylated water-soluble derivatives of 2-DG and present a detailed 1H and 13C NMR analysis of all final products. X-ray diffraction analysis has been performed for compound WP1122 that was selected for detailed preclinical and subsequent clinical evaluation as potential anticancer or antiviral agent.

Efficient One-Pot Synthesis of Novel Caffeic Acid Derivatives as Potential Antimalarials.

New protocol for the preparation of the novel caffeic acid derivatives using the Wittig reaction has been applied to follow the principles of green chemistry. The compounds have been evaluated against chloroquine-sensitive and chloroquine-resistant P. falciparum strains. Their cytotoxicity to normal human dermal fibroblasts and their propensity to induce hemolysis have been also determined. Ethyl (2E)-3-(2,3,4-trihydroxyphenyl)-2-methylpropenoate has exhibited the highest antiplasmodial activity against P. falciparum strains without the cytotoxic and hemolytic effects. This derivative is significantly more potent than caffeic acid parent structure. The application of our one-step procedure has been shown to be rapid and efficient. It allows for an easy increase of input data to refine the structure-activity relationship model of caffeates as the antimalarials. The one-step approach meets the conditions of "atom economy" and eliminates hazardous materials. Water has been used as the effective medium for the Wittig reaction to avoid toxic organic solvents.

Psychomotor functions and interval timing in patients receiving intravenous anesthesia for endoscopic procedures: the pilot study.

Introduction. The aim of this study was to evaluate two measures in a cognitive examination: psychomotor function and the perception of time (PT) in patients after intravenous anesthesia for endoscopic procedures. Material and Methods. We tested 23 anesthetized patients (Anesthesia Group, AG) and 17 not anesthetized patients (Control Group, CG). The Dufour Cross-Shaped Apparatus (DA) was used to assess quick reactions. Perception of time (PT) was measured for 1-, 2-, 5-, and 7-second intervals. The tests were performed before the anesthesia was administered and 1.5, 3, and 6 hours after the procedure was completed. Results. The intervals that were generated and the reproduced visual stimuli were shorter than the patterns. The reproduced 1- and 2-second auditory stimuli were longer than the patterns. The remaining reproduced auditory impulses were shorter than the patterns. Conclusions. In anesthetized patients, quick psychomotor reactions and the ability to time intervals are preserved 1.5 h and later after intravenous anesthesia for endoscopy.

The Use of the ICF Classification Sheet to Assess Cognitive-Behavioral Disorders and Verbal Communication in Patients after Ischemic and Hemorrhagic Stroke during Rehabilitation.

Background: In patients after experiencing stroke, the cognitive-behavioral deficits and disorders of verbal communication limit the effectiveness of rehabilitation. The key is to diagnose them at an early stage of rehabilitation and to implement appropriate psychological and speech therapy. Objective: Identify differences in the frequency and effectiveness of cognitive-behavioral disorder therapy depending on the clinical type of stroke, assessed before and after rehabilitation treatment, and their presentation using the ICF (International Classification of Functioning, Disability, and Health) classification. Materials and Methods: The study was prospective and included the analysis of cognitive-behavioral and verbal communication disorders. The study consisted of 47 patients after intracerebral hemorrhage (ICH) and 47 patients after an ischemic stroke (IS) before the implementation of rehabilitation and after completing a 4-week rehabilitation. Results: In the group after ICH, psychological therapy significantly reduced the disturbances of consciousness and orientation (p < 0.001) and improved the speed of performing tasks in tests (p < 0.001). In patients after IS and ICH, memory and attention function improved significantly (p < 0.001). Moreover, in patients after ICH, language function deficits decreased significantly (p = 0.018). Mood disturbances were maintained in 17% of patients after ICH and 40% of patients after IS (p = 0.007). Speech therapy reduced speech articulation disorders and aphasia in 85% of patients after ICH (p = 0.001) and in 68% of patients after IS (p = 0.033). Conclusions: The frequency and type of cognitive-behavioral and verbal communication disorders vary depending on the history of ICH or IS. The ICF classification may be useful in assessing and analyzing cognitive-behavioral and verbal communication disorders, which may lead to the implementation of appropriate psychological and speech therapy at an early stage of rehabilitation and increase the effectiveness of the therapy.

Antioxidant activity of novel diosgenin derivatives: Synthesis, biological evaluation, and in silico ADME prediction.

A series of novel diosgenin (DSG) derivatives has been synthesized and tested in vitro for their antioxidant activity. Initially, four analogues have been evaluated for their cytotoxicity using normal human skin fibroblast (NHDF) as model cells. As a result, 84% of NHDF cells were still alive at 5 µM, so these compounds can be considered as innoxious to fibroblasts at this concentration. Then, hemolytic activity against human erythrocytes was studied in order to evaluate the potential impact of tested compounds against normal host cells. The result < 5% of hemolysis rates suggest no lytic activity for most compounds. After that, the main test - evaluation the antioxidant effect of DSG and its new derivatives against lipid peroxidation in the o/w emulsion model - was performed. The most promising compound (8) exhibited the significant antioxidant activity and the biocompatibility towards normal human dermal fibroblasts and red bloods cells. This p-aminobenzoic derivative revealed 61.6% blocking of induced lipid oxidation. Furthermore, eleven predicted ADME properties were predicted for all tested compounds and revealed that they are in compliance with drug-likeness criteria.

Structure-Activity Relationship of Hydroxycinnamic Acid Derivatives for Cooperating with Carnosic Acid and Calcitriol in Acute Myeloid Leukemia Cells.

Plant phenolic compounds have shown the ability to cooperate with one another at low doses in producing enhanced anticancer effects. This may overcome the limitations (e.g., poor bioavailability and high-dose toxicity) in developing these agents as cancer medicines. We have previously reported that the hydroxycinnamic acid derivative (HCAD) methyl-4-hydroxycinnamate and the phenolic diterpene carnosic acid (CA) can synergistically induce massive calcium-dependent apoptosis in acute myeloid leukemia (AML) at non-cytotoxic concentrations of each agent. Here, we explored the chemical nature of the synergy between HCADs and either CA, in inducing cytotoxicity, or the active metabolite of vitamin D (calcitriol), in enhancing the differentiation of AML cells. This was done by determining the structure-activity relationship of a series of hydroxycinnamic acids and their derivatives (methyl hydroxycinnamates and hydroxybenzylideneacetones) in combination with CA or calcitriol. The HCAD/CA synergy required the following critical structural elements of an HCAD molecule: (a) the para-hydroxyl on the phenolic ring, (b) the carbon C7-C8 double bond, and (c) the methyl-esterified carboxyl. Thus, the only HCADs capable of synergizing with CA were found to be methyl-4-hydroxycinnamate and methyl ferulate, which also most potently enhanced calcitriol-induced cell differentiation. Notably, the C7-C8 double bond was the major requirement for this HCAD/calcitriol cooperation. Our findings may contribute to the rational design of novel synergistically acting AML drugs based on prototype combinations of HCADs with other agents studied here.

[Simulator sickness and the Simulator Sickness Questionnaire in Polish practice. A study involving professional drivers subject to compulsory initial and periodic qualification courses]. / Choroba symulatorowa i Simulator Sickness Questionnaire w polskiej praktyce. Badania kierowców zawodowych podlegajacych obowiazkowym kursom kwalifikacji wstepnej i okresowej.

BACKGROUND: A phenomenon of simulator sickness is measurable in terms of physiological symptoms. The article presents the practical use of the Simulator Sickness Questionnaire (SSQ) in post-exposure research, together with feedback given by the examined drivers. MATERIAL AND METHODS: The study was conducted on the AutoSim AS 1600 simulator, and involved 130 drivers attending preliminary and periodic qualification courses in road transportation. The following tools were used throughout the research: the SSQ by Kennedy et al., translated into Polish by Biernacki et al. (with symptoms including nausea, oculomotor disturbances & disorientation symptoms, and the SSQ total), and a tool evaluating the SSQ (comprehensibility and time consumption on a 1-6 scale). RESULTS: In the study group (N = 130), some statistically significant differences in the SSQ results were observed. Among younger drivers (<29.5 years old) an increased intensity of the simulator sickness symptoms after simulation was recorded (nausea and the SSQ total), and among older drivers (>29.5 years old) - the disorientation symptoms after simulation. The length of sleep and the quality assessment of the conducted task were higher in the asymptomatic groups. Also, the results indicate a positive reception of the tool by the examined individuals (N = 113), with time consumption marked as low (M = 2.44 on a 1-6 scale) and comprehensibility as high (M = 5.62 on a 1-6 scale). CONCLUSIONS: The research indicates the occurrence of simulator sickness symptoms even in simulators, which accurately reflect vehicle movements. The feedback given by the examined individuals, together with the level of involvement in the SSQ use, indicates a positive reception of the tool. Med Pr. 2020;71(1):47-58.