The influence of excessive stress on medical students in the Czech Republic - national sample.

PURPOSE: The Czech Republic has been dealing with a long-term shortage of doctors, which, according to demographic forecasts, will continue to worsen due to the retirement of stronger generations of doctors in contrast to the gradual aging of the population, which will require more health care over time. The country´s political set is trying to respond to this shortage and demographic forecasts by gradually increasing financial funding of medical faculties with the aim of increasing the number of graduates of the program in the field of general medicine. METHODS: Anonymous questionnaire survey was conducted among students and graduates of general medicine at all eight Czech medical faculties. A total of 3183 respondents participated in the survey. There were 2843 medical students, which represents approximately 28% of all medical students in the Czech Republic. The distribution of respondents within the study years was approximately even and approximately corresponded to the real distribution of students between individual faculties in country, which makes survey a national sample. The statistical processing was performed in the statistical software R. Apart from the basic comparison using percentage relative frequencies and Pearson´s chi-squared test, in this study we used Odds ratios (OR) with CI 0,95 from logistic regression model for a better interpretation of some outputs. RESULTS: The results show that the vast majority of Czech medical students experience excessive stress during their studies, which increases the risk of students´ somatic problems (OR = 4.89, CI 0.95 = (4.11;5.83), p < 0.001)., targeted alcohol use (OR = 2.29, CI 0.95 = (1.73;3.04), p < 0,001) and the use of anxiolytic or antidepressant medication to reduce it (OR = 2.99, CI 0.95 = (2.24;4.01), p < 0.001). Students experiencing higher levels of excessive stress are more likely to leave their studies based on their own decision (4.20 (CI 0.95 (3.39;5.19), p < 0.001) and not to enter clinical practice after graduation (OR = 2.62, CI 0.95 = (2.06;3.33), p < 0.001). CONCLUSIONS: The survey shows the need for an open discussion at the highest level about the possibilities of reasonable reduction of unnecessary stress during medical studies. Medical students in the Czech Republic are exposed to excessive stress with all the consequences described above. All that remains is to state the existence of unnecessary components of stress, which represent an opportunity to reduce it, thereby achieving better conditions for studying, improvement in the staff situation in the Czech healthcare system and a reduction in inefficiently spent financial resources for the education of young doctors. TRIAL REGISTRATION: No registration.

Lithium chloride antileukemic activity in acute promyelocytic leukemia is GSK-3 and MEK/ERK dependent.

We recently identified that the MEK/ERK1/2 pathway synergized with retinoic acid (RA) to restore both transcriptional activity and RA-induced differentiation in RA-resistant acute promyelocytic leukemia (APL) cells. To target the MEK/ERK pathway, we identified glycogen synthase kinase-3ß (GSK-3ß) inhibitors including lithium chloride (LiCl) as activators of this pathway in APL cells. Using NB4 (RA-sensitive) and UF-1 (RA-resistant) APL cell lines, we observed that LiCl as well as synthetic GSK-3ß inhibitors decreased proliferation, induced apoptosis and restored, in RA-resistant cells, the expression of RA target genes and the RA-induced differentiation. Inhibition of the MEK/ERK1/2 pathway abolished these effects. These results were corroborated in primary APL patient cells and translated in vivo using an APL preclinical mouse model in which LiCl given alone was as efficient as RA in increasing survival of leukemic mice compared with untreated mice. When LiCl was combined with RA, we observed a significant survival advantage compared with mice treated by RA alone. In this work, we demonstrate that LiCl, a well-tolerated agent in humans, has antileukemic activity in APL and that it has the potential to restore RA-induced transcriptional activation and differentiation in RA-resistant APL cells in an MEK/ERK-dependent manner.

Use of stabilometric platform and visual feedback in rehabilitation of patients after the brain injury.

Rehabilitation of patients after the brain injury requires employing of all available mechanisms of neuroplasticity. To achieve it, the voluntary activation of brain systems that are involved in the signal processing, represents the most effective tool. The control of balance is a complex neuronal mechanism based on unconditioned and conditioned reflexes, as well as on the actual cognitive processes. As it requires participation of several brain regions, training of the posture support mechanisms can provide a highly effective tool for rehabilitation. The aim of the study was to develop methods for the long-term follow up and training of the balance skills in patients with different types of brain impairment. To obtain standard data, the stabilometric platform Posturograph STP-03 and special examination programs were also used in the study of the equilibrium skill training by healthy volunteers. For the assessment of the learning efficiency two criteria from the recorded data were used - the velocity of adjustment of the gravity centre and the accuracy of the movements. Stabilometric platform was used also for the balance skill training with the visual biofeedback. Our results show that the proposed program for the equilibrium skill training offers a comparatively simple method of the adequate duration with numerical and graphical output, which allows fast interpretation of the treatment results. The synoptic form of results can also stimulate the patient's motivation during the long-term training for the mobility improvement.

[Characterization of null alleles in human histocompatibility complex antigens (HLA)]. / Charakterizace nulových alel v komplexu lidských histokompatibilních antigenu (HLA).

The widespread application of DNA techniques in medicine and biology has allowed the typing of human leukocyte antigens (HLA) at the molecular level. Comparative studies between serological and molecular biology methods have shown the existence of null alleles, which code HLA antigens with low or no cell surface expression. Null alleles are not detectable by standard serological typing methods and may be overlooked/or incorrectly assigned by available DNA methods. Although null alleles are infrequent in human populations, they should not be ignored. Errors in typing of null alleles may cause complications in the evaluation of HLA matching of donor/recipient pairs that were originally considered HLA-compatible. The detection of null alleles and their frequency in various populations requires typing of a large number of individuals by both serological and DNA-based methods. Knowledge of the haplotype(s) associated with null alleles may be helpful for their identification. For this purpose, it is necessary to perform family studies.

Structural homology between elongation factors EF-Tu from Bacillus stearothermophilus and Escherichia coli in the binding site for aminoacyl-tRNA.

Elongation factor EF-Tu (Mr approximately equal to 50 000) and elongation factor EF-G (Mr approximately equal to 78 000) were isolated from Bacillus stearothermophilus in a homogeneous form. The ability of EF-Tu to participate in protein synthesis is rapidly inactivated by N-tosyl-L-phenyl-alanylchloromethane (Tos-PheCH2Cl). EF-Tu X GTP is more susceptible to the inhibition by Tos-PheCH2Cl than is EF-Tu X GDP. Tos-PheCH2Cl forms a covalent equimolar complex with the factor by reacting with a cysteine residue in its molecule. The labelling of EF-Tu by the reagent irreversibly destroys its ability to bind aminoacyl-tRNA, which in turn protects the protein from this inactivation. This indicates that the modification of EF-Tu by Tos-PheCH2Cl occurs at the aminoacyl-tRNA binding site of the protein. To identify and characterize the site of aminoacyl-tRNA binding in EF-Tu, the factor was labelled with [14C]Tos-PheCH2Cl, digested with trypsin, the resulting peptides were separated by high-performance liquid chromatography and the sequence of the radioactive peptide was determined. The peptide has identical structure with an Escherichia coli EF-Tu tryptic peptide comprising the residues 75-89 and the Tos-PheCH2Cl-reactive cysteine at position 81 [Jonák, J., Petersen, T. E., Clark, B. F. C. and Rychlík, I. (1982) FEBS Lett. 150, 485-488]. Experiments on photo-oxidation of EF-Tu by visible light in the presence of rose bengal dye showed that there are apparently two histidine residues in elongation factor Tu from B. stearothermophilus which are essential for the interaction with aminoacyl-tRNA. This is clearly reminiscent of a similar situation in E. coli EF-Tu [Jonák, J., Petersen, T. E., Meloun, B. and Rychlík, I. (1984) Eur. J. Biochem. 144, 295-303]. Our results provide further evidence for the conserved nature of the site of aminoacyl-tRNA binding in elongation factor EF-Tu and show that Tos-PheCH2Cl reagent might be a favourable tool for the identification of the site in the structure of prokaryotic EF-Tus.