BACKGROUND: Given the critical role of general practitioners (GPs), their insufficient medical density and the adverse effects of burnout on both practitioners and the quality of care provided, the prevalence estimates of GP burnout reported in the literature are highly concerning. This nationwide study builds on a 2023 survey that revealed a significant burden of burnout among Czech GPs. The primary objectives were to analyse the prevalence and determinants of burnout and to examine potential trends over time. METHODS: In April 2024, 2,500 randomly selected GPs were emailed the Maslach Burnout Inventory - Human Services Survey for Medical Personnel, supplemented with sociodemographic and job-related questions. The statistical analysis included a comparison with an identical study conducted a year earlier. RESULTS: Of the 765 completed responses (542 females, 223 males; mean age 55.5 years), 19.7% of the GPs experienced burnout in all three dimensions, 23% in two, 28.5% in one, and 28.8% in no dimension. Similar to 2023, the most common burnout dimension was a lack of personal accomplishment (PA, 52.2%), followed by emotional exhaustion (EE, 45.9%) and depersonalization (DP, 35.7%). Male and employed GPs experienced greater degrees of DP, while practice owners were more susceptible to EE. A positive dependence of burnout on the number of listed patients was identified. The proportion of GPs experiencing burnout across all dimensions decreased by 2.1% from 2023 to 2024 (p = 0.232), primarily in DP. Additionally, a 6.7% increase in GPs showing no signs of burnout in all dimensions (p = 0.002) further supported this positive trend. CONCLUSIONS: Between 2023 and 2024, the prevalence of burnout among GPs exhibited a modest decline. Nonetheless, it persists at almost 20%. Ensuring a sufficiently dense network of GPs, providing adequate resource allocation, and raising awareness of their importance are essential measures.

• MeSH
• depersonalizace epidemiologie   psychologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• pracovní uspokojení MeSH
• praktičtí lékaři * psychologie   MeSH
• prevalence MeSH
• profesionální vyhoření * epidemiologie   psychologie   MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

MicroRNA hsa-miR-29 was connected to a number of malignancies. Its target genes are many, among them Mcl-1 that is expressed in three possible isoforms, one of which is anti-apoptotic and another one pro-apoptotic. Ratio of these two isoforms appears to affect cell response to external stimuli. We have demonstrated that miR-29b enhanced etoposide toxicity in HeLa cell line by modulating this ratio of Mcl-1 isoforms. However, it is not known whether the described miR-29 effect is common to various cancer types or even have the opposite effect. This represents a significant problem for possible future applications. In this report, we demonstrate that miR-29b affects toxicity of 60 μM etoposide in cell lines derived from selected malignancies. The mechanism, however, differs among the cell lines tested. Hep G2 cells demonstrated similar effect of miR-29b on etoposide toxicity as was described in HeLa cells, i.e. modulation of Mcl-1 expression. Target protein down-regulated by miR-29b resulting in enhanced etoposide toxicity in Caco-2 cells was, however, Bcl-2 protein. Moreover, H9c2, Hek-293 and ARPE-19 cell lines selected as a representatives of non-malignant cells, showed no effect of miR-29b on etoposide toxicity. Our data suggest that miR-29b could be a common enhancer of etoposide toxicity in malignant cells due to its modulation of Bcl family proteins.

• MeSH
• apoptóza účinky léků   genetika   MeSH
• buňky Hep G2 MeSH
• Caco-2 buňky MeSH
• etoposid * toxicita   farmakologie   MeSH
• fytogenní protinádorové látky farmakologie   toxicita   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• protein MCL-1 * genetika   metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug-drug interactions involving IP6 are low.

• MeSH
• kyselina fytová * MeSH
• lidé MeSH
• messenger RNA MeSH
• savci MeSH
• simulace molekulového dockingu MeSH
• systém (enzymů) cytochromů P-450 MeSH
• xenobiotika * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Background: Chronic wounds present a significant clinical, social, and economic challenge. This study aimed to objectify the risk factors of healing outcomes and the duration of chronic wounds from various etiologies. Methods: Patients treated for non-healing wounds at the surgical outpatient clinic of the Olomouc Military Hospital were involved. Data from patients treated between 8/2021 and 9/2023 were selected. Patients were mostly treated as outpatients, with microbiological follow-up indicated in cases of advanced signs of inflammation. Results: There were 149 patients who met our selection criteria (the mean age was 64.4 years). Predominant causes of wounds involved diabetes (30.9%), post-trauma (25.5%), pressure ulcers (14.8%), surgical site infections (14.8%), and vascular ulcers (14.1%). Patient outcomes included wound resolution in 77.2% of patients (with a mean healing time of 110.9 days), amputation in 14.1%, and wound-related death in 8.7% of patients. Non-healing cases (amputation/death) were predicted by several local factors including an initial depth greater than 1 cm, wound secretion, inflammatory base, and a maximum wound size. Systemic factors included most strongly clinically manifested atherosclerosis and its risk factors. Of the 110 swabs performed, 103 identified at least 1 bacterial genus. The dominant risk factor for a prolonged healing duration was bacterial infection. Wounds contaminated by Proteus or Pseudomonas had prolonged healing times of 87 days (p = 0.02) and 72 days (p = 0.045), respectively. Conclusions: The early identification of local and systemic risk factors contributes to the successful resolution of chronic wounds and a reduced duration of healing.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

• MeSH
• antiflogistika terapeutické užití   farmakologie   MeSH
• chlorhexidin terapeutické užití   farmakologie   analogy a deriváty   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• faktor 2 související s NF-E2 MeSH
• fibroblasty * účinky léků   MeSH
• gingiva * účinky léků   MeSH
• gingivitida * farmakoterapie   MeSH
• hemoxygenasa-1 MeSH
• interleukin-6 analýza   MeSH
• interleukin-8 účinky léků   MeSH
• kanabidiol * farmakologie   terapeutické užití   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• parodontitida farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

The ultraviolet (UV) part of solar radiation can permanently affect skin tissue. UVA photons represent the most abundant UV component and stimulate the formation of intracellular reactive oxygen species (ROS), leading to oxidative damage to various biomolecules. Several plant-derived polyphenols are known as effective photoprotective agents. This study evaluated the potential of quercetin (QE) and its structurally related flavonoid taxifolin (TA) to reduce UVA-caused damage to human primary dermal fibroblasts (NHDF) and epidermal keratinocytes (NHEK) obtained from identical donors. Cells pre-treated with QE or TA (1 h) were then exposed to UVA light using a solar simulator. Both flavonoids effectively prevented oxidative damage, such as ROS generation, glutathione depletion, single-strand breaks formation and caspase-3 activation in NHDF. These protective effects were accompanied by stimulation of Nrf2 nuclear translocation, found in non-irradiated and irradiated NHDF and NHEK, and expression of antioxidant proteins, such as heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and catalase. For most parameters, QE was more potent than TA. On the other hand, TA demonstrated protection within the whole concentration range, while QE lost its protective ability at the highest concentration tested (75 μM), suggesting its pro-oxidative potential. In summary, QE and TA demonstrated UVA-protective properties in NHEK and NHDF obtained from identical donors. However, due to the in vitro phototoxic potential of QE, published elsewhere and discussed herein, further studies are needed to evaluate QE safety in dermatological application for humans as well as to confirm our results on human skin ex vivo and in clinical trials.

• MeSH
• fibroblasty MeSH
• flavonoidy * metabolismus   MeSH
• keratinocyty MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• oxidační stres MeSH
• quercetin * analogy a deriváty   farmakologie   MeSH
• ultrafialové záření MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

High vaccination coverage among healthcare workers (HCWs) is crucial for managing the COVID-19 pandemic. The aim was to determine the demand for vaccination among all employees (n = 4553) of a tertiary care hospital after several weeks of the vaccine's availability, and to analyze motives for acceptance and reasons for hesitancy through an anonymous online questionnaire. Upon the completion of data collection, the hospital's vaccination coverage was at 69.8%. A total of 3550 completed questionnaires were obtained (2657 from vaccinated, 893 from unvaccinated employees). Significant predictors of vaccine acceptance were: age (odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01-1.02), sex (OR (females) 0.58, 95% CI 0.45-0.75), job type (OR (non-physician HCWs) 0.54, 95% CI 0.41-0.72; OR (non-HCWs) 0.51, 95% CI 0.37-0.71), fear of COVID-19 (OR 1.4, 95% CI 1.34-1.46), history of COVID-19 (OR 0.41, 95% CI 0.34-0.49) and of influenza vaccination (OR 2.74, 95% CI 2.12-3.57). The most frequent motive for acceptance was the effort to protect family members (84%), while concerns about vaccine safety and side effects (49.4%), followed by distrust in the vaccine's efficacy (41.1%) were the top reasons for hesitancy. To increase vaccination coverage among HCWs, it is necessary to raise awareness of vaccine safety and efficacy.

• Publikační typ
• časopisecké články MeSH

2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the biotransformation of pure 2,3-dehydrosilybin A and 2,3-dehydrosilybin B in isolated human hepatocytes, and we also aimed to identify human UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) with activity toward their respective enantiomers. After incubation with hepatocytes, both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B were converted to hydroxyl derivatives, methylated hydroxyl derivatives, methyl derivatives, sulfates, and glucuronides. The products of direct conjugations predominated over those of oxidative metabolism, and glucuronides were the most abundant metabolites. Furthermore, we found that recombinant human UGTs 1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 were capable of catalyzing the glucuronidation of both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B. UGTs 1A1 and 1A7 showed the highest activity toward 2,3-dehydrosilybin A, and UGT1A9 showed the highest activity toward 2,3-dehydrosilybin B. The sulfation of 2,3-dehydrosilybin A and B was catalyzed by SULTs 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C2, 1C4, and 1E1, of which SULT1A3 exhibited the highest activity toward both enantiomers. We conclude that 2,3-dehydrosilybin A and B are preferentially metabolized by conjugation reactions, and that several human UGT and SULT enzymes may play a role in these conjugations.

• Publikační typ
• časopisecké články MeSH

Polyphenols, secondary metabolites of plants, exhibit different anti-cancer and cytoprotective properties such as anti-radical, anti-angiogenic, anti-inflammation, or cardioprotective. Some of these activities could be linked to modulation of miRNAs expression. MiRNAs play an important role in posttranscriptional regulation of their target genes that could be important within cell signalling or preservation of cell homeostasis, e.g., cell survival/apoptosis. We evaluated the influence of a non-toxic concentration of taxifolin and quercetin on the expression of majority human miRNAs via Affymetrix GeneChip™ miRNA 3.0 Array. For the evaluation we used two cell models corresponding to liver tissue, Hep G2 and primary human hepatocytes. The array analysis identified four miRNAs, miR-153, miR-204, miR-211, and miR-377-3p, with reduced expression after taxifolin treatment. All of these miRNAs are linked to modulation of ZEB2 expression in various models. Indeed, ZEB2 protein displayed upregulation after taxifolin treatment in a dose dependent manner. However, the modulation did not lead to epithelial mesenchymal transition. Our data show that taxifolin inhibits Akt phosphorylation, thereby diminishing ZEB2 signalling that could trigger carcinogenesis. We conclude that biological activity of taxifolin may have ambiguous or even contradictory outcomes because of non-specific effect on the cell.

• MeSH
• apoptóza účinky léků   MeSH
• buňky Hep G2 metabolismus   MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• exprese genu účinky léků   genetika   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• lidé MeSH
• mikro RNA účinky léků   genetika   MeSH
• pohyb buněk účinky léků   MeSH
• polyfenoly farmakologie   MeSH
• primární buněčná kultura MeSH
• proliferace buněk účinky léků   MeSH
• quercetin analogy a deriváty   metabolismus   farmakologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• signální transdukce genetika   MeSH
• transkripční faktor Zeb2 účinky léků   metabolismus   MeSH
• transkriptom účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The yeast Magnusiomyces capitatus is an opportunistic human pathogen causing rare yet severe infections, especially in patients with hematological malignancies. Here, we report the 20.2 megabase genome sequence of an environmental strain of this species as well as the genome sequences of eight additional isolates from human and animal sources providing an insight into intraspecies variation. The distribution of single-nucleotide variants is indicative of genetic recombination events, supporting evidence for sexual reproduction in this heterothallic yeast. Using RNAseq-aided annotation, we identified genes for 6518 proteins including several expanded families such as kexin proteases and Hsp70 molecular chaperones. Several of these families are potentially associated with the ability of M. capitatus to infect and colonize humans. For the purpose of comparative analysis, we also determined the genome sequence of a closely related yeast, Magnusiomyces ingens. The genome sequences of M. capitatus and M. ingens exhibit many distinct features and represent a basis for further comparative and functional studies.

• MeSH
• anotace sekvence MeSH
• antifungální látky farmakologie   MeSH
• faktory virulence MeSH
• fenotyp MeSH
• fylogeneze MeSH
• genom fungální * MeSH
• genomika * metody   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• multigenová rodina MeSH
• mykózy mikrobiologie   MeSH
• oportunní infekce mikrobiologie   MeSH
• rekombinace genetická MeSH
• Saccharomycetales klasifikace   genetika   růst a vývoj   patogenita   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH