The unified state qualification exam STEP-1 as a marker of the success of the education of pediatric doctors in Ukraine and Bogomolets National Medical University.

BACKGROUND: Ukraine's higher medical education goes deeper and deeper every year in the European integration processes in the field of «Health Care¼ knowledge. Since 2005, the integrated license integrated exam STEP "General medical training" has been introduced in the country to diagnose the quality of training of specialists in all medical specialties. Since 2019, Ukraine, unlike other countries in Europe and the world, has been training specialists in the specialty "Pediatrics" at the stage of undergraduate training. The quality control of the training of specialists is carried out in the form of passing the Unified State Qualification Exam STEP (USQE STEP) separately for each medical specialty (Medicine and Pediatrics). Therefore, the purpose of our research is to conduct a comparative analysis of the results of the success of the first stage of the USQE STEP-1 by students of higher medical education in the specialty "Pediatrics" with the specialty "Medicine" in Ukraine and in the Bogomolets National Medical University (Bogomolets NMU). METHODS: Analytical references to the results of the first stage of the USQE STEP-1 for the students who have completed theoretical medical disciplines specialty "Pediatrics" and the specialty "Medicine" in Ukraine and Bogomolets NMU, which are provided by the Testing Center at the Ministry of Health of Ukraine. Тhe statistical significance of comparative indicators was proved using Fisher's test, with a statistical error that corresponded to the specified value for ≤ 0.05. RESULTS: It is shown that in 2022, applicants of higher medical education of Ukraine with the specialty "Pediatrics" improved the overall success rate by 8.4%, and the success rate of subtests by an average of 10.5%, despite the state of war in Ukraine. The exception was the results of the licensing exam for the subtest component "Biochemistry": compared to 2021, the pass rate decreased by 3.6% in the specialty "Medicine" and by 6.4% in the specialty "Pediatrics". At Bogomolets NMU, the leaders of 2022 were the students of the "Pediatrics" specialty, their success rate is 2% higher than that of the "Medicine" specialty. CONCLUSIONS: The analysis of the results of USQE STEP-1 by applicants of higher medical education of the specialties "Pediatrics" and "Medicine" in Ukraine showed the effectiveness of the selection of the specialty "Pediatrics" into a separate section of the training of specialists at the undergraduate level in the field of "Health Care". Using the methods of mathematical statistics, the effectiveness of organizational methodological techniques in the organization of the educational process in the conditions of the martial law of Ukraine and Bogomolets NMU as a leader in the training of specialists in Pediatric doctors has been proved.

Nicotinamide prevention in diabetes-induced alterations in the rat liver.

Objective. The study was performed to elucidate whether nicotinamide (NAm) can attenuate the diabetes-induced liver damage by correction of ammonia detoxifying function and disbalance of NAD-dependent processes in diabetic rats. Methods. After four weeks of streptozotocin-induced diabetes, Wistar male rats were treated for two weeks with or without NAm. Urea concentration, arginase, and glutamine synthetase activities, NAD+ levels, and NAD+/NADH ratio were measured in cytosolic liver extracts. Expression of parp-1 gene in the liver was estimated by quantitative polymerase chain reaction and PARP-1 cleavage evaluated by Western blotting. Results. Despite the blood plasma lipid peroxidation products in diabetic rats were increased by 60%, the activity of superoxide dismutase (SOD) was reduced. NAm attenuated the oxidative stress, but did not affect the enzyme activity in diabetic rats. In liver of the diabetic rats, urea concentration and arginase activity were significantly higher than in the controls. The glutamine synthetase activity was decreased. Decline in NAD+ level and cytosolic NAD+/NADH ratio in the liver of diabetic rats was observed. Western blot analysis demonstrated a significant up-regulation of PARP-1 expression accompanied by the enzyme cleavage in the diabetic rat liver. However, no correlation was seen between mRNA expression of parp-1 gene and PARP-1 protein in the liver of diabetic rats. NAm markedly attenuated PARP-1 cleavage induced by diabetes, but did not affect the parp-1 gene expression. Conclusions. NAm counteracts diabetes-induced impairments in the rat liver through improvement of its detoxifying function, partial restoration of oxidative stress, NAD+ level, normalization of redox state of free cytosolic NAD+/NADH-couples, and prevention of PARP-1 cleavage.

Modulatory effects of vitamin B3 and its derivative on the levels of apoptotic and vascular regulators and cytoskeletal proteins in diabetic rat brain as signs of neuroprotection.

BACKGROUND: Beneficial effects of nicotinamide (NAm) and its derivates have been earlier shown in animal models of diabetes mellitus (DM), but the mechanisms of their neuroprotective activities are still largely unknown. The aim of the present study was to investigate if NAm and conjugate of nicotinic acid with gamma-aminobutyric acid (N-GABA) are able to modulate expression levels of apoptosis regulators, angiogenesis-related molecules, and specific cytoskeletal proteins in diabetic rat brain. METHODS: After six weeks of streptozotocin induced type 1 DM, rats were daily administered either by NAm (100 mg/kg) or N-GABA (55 mg/kg) intraperitoneally for two weeks. Protein levels were assessed by western blot and immunohistochemistry. RESULTS: Both NAm and N-GABA down-regulated NF-κB and Bax levels in diabetic rat brain, suggesting their anti-apoptotic activities. Tested compounds normalized VEGF and nNOS contents improving pro-angiogenic signaling reduced by hyperglycemia. Western blot showed marked up-regulation of astroglial marker GFAP and lowering neurofilament protein levels in DM group, confirmed immunohistochemically, indicating the development of reactive astrogliosis as a major response to diabetes-induced neurodegeneration. NAm had no effects on GFAP and Nf-L levels in the diabetic brain, while N-GABA increased their expression. Inversely, NAm and N-GABA dramatically reduced enhanced levels of GFAP and Nf-L found in the blood serum of diabetic rats, providing for the first time strong evidence for preserving blood-brain barrier integrity by studied compounds. CONCLUSION: Thus, NAm and N-GABA may exert neuroprotective effects by decreasing pro-apoptotic regulators levels and improving expression of angiogenic and cytoskeletal proteins impaired by hyperglycemia in rat brain.

The parp-1 and bax genes as potential targets for treatment of the heart functioning impairments induced by type 1 diabetes mellitus.

Objectives. The present study was designed to assess whether apoptosis-related genes as parp-1 and bax could be targets for treatment of diabetes mellitus and whether vitamin D may exert beneficial effects. Methods. Vitamin D3 treatment for 4 weeks, starting after 4 weeks of the diabetes duration. The expression of parp-1 and bax genes was estimated on mRNA levels using real time quantitative polymerase chain reaction. Results. After 8 weeks, diabetic rats had weight loss, while blood glucose was increased about 4.9-fold compared to control group. Vitamin D3 administration to diabetic animals had no effect on these parameters. It was found that total serum alkaline phosphatase activity was significantly elevated in diabetic rats as compared to control animals and was restored by vitamin D3. Diabetes was accompanied by reduction of nicotinamidadenindinucleotide, a substrate of poly-ADP-ribosylation, level by 31.7% as compared to control rats, which was not reversed in response to vitamin D3 treatment. In diabetic hearts, the mRNA expression level of parp-1 gene was 2.8-fold higher compared to control rats and partially decreased by vitamin D3 treatment. Less significant alterations were observed in diabetic hearts for the mRNA expression level of bax gene that was 2.0-fold higher compared to control animals and vitamin D3 normalized it. These results indicate that cardiomyocytes have a tendency to apoptosis. Conclusions. The findings suggest that investigated genes can be targets at the transcriptional level for vitamin D action that may be contributed to the improving metabolic/signaling pathways induced by diabetes mellitus.

Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats.

Diabetic retinopathy (DR) is a multifactorial disease characterized by reactive gliosis and disbalance of angiogenesis regulators, contributing to endothelial dysfunction and microvascular complications. This study was organized to elucidate whether poly(ADP-ribose) polymerase-1 (PARP-1) inhibition could attenuate diabetes-induced damage to macroglia and correct angiogenic disbalance in diabetic rat retina. After 8 weeks of streptozotocin (STZ)-induced diabetes, Wistar male rats were treated with PARP-1 inhibitors, nicotinamide (NAm) or 3-aminobenzamide (3-AB) (100 and 30 mg/kg/daily i.p., respectively), for 14 days. After the 10-weeks experiment period, retinas were undergone an immunohistochemical staining for glial fibrillary acidic protein (GFAP), while western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of PARP-1, poly(ADP-ribosyl)ated proteins (PARs), GFAP, and angiostatin isoforms. Diabetes induced significant up-regulation and activation of retinal PARP-1, reactive gliosis development, and GFAP overexpression compared to non-diabetic control. Moreover, extensive fragmentation of both PARP-1 and GFAP (hallmarks of apoptosis and macroglia reactivation, respectively) in diabetic retina was also observed. Levels of angiostatin isoforms were dramatically decreased in diabetic retina, sustaining aberrant pro-angiogenic condition. Both NAm and 3-AB markedly attenuated damage to macroglia, evidenced by down-regulation of PARP-1, PARs and total GFAP compared to diabetic non-treated group. PARP-1-inhibitory therapy prevented formation of PARP-1 and GFAP cleavage-derived products. In retinas of anti-PARP-treated diabetic animals, partial restoration of angiostatin's levels was shown. Therefore, PARP-1 inhibitors counteract diabetes-induced injuries and manifest retinoprotective effects, including attenuation of reactive gliosis and improvement of angiogenic status, thus, such agents could be considered as promising candidates for DR management.