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
• Depersonalization epidemiology   psychology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Job Satisfaction MeSH
• General Practitioners * psychology   MeSH
• Prevalence MeSH
• Burnout, Professional * epidemiology   psychology   MeSH
• Surveys and Questionnaires MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

• MeSH
• Prolactin-Releasing Hormone pharmacology   therapeutic use   MeSH
• Hypothalamus MeSH
• Humans MeSH
• Mice MeSH
• Neurogenesis MeSH
• Neuropeptides * MeSH
• Obesity * drug therapy   MeSH
• Body Weight MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Electrocardiography MeSH
• Arrhythmias, Cardiac MeSH
• Publication type
• Handbook MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• kardiologie

INTRODUCTION: The benefit of secondary prevention in hypertensive patients with peripheral arterial disease (PAD) is based on continual simultaneous taking of statins, antiplatelet agents and antihypertensive agents, preferably angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Our study was aimed at a) the analysis of the extent of non-persistence with multiple medication classes, and b) identifying factors associated with the likelihood of non-persistence. METHODS: In our cohort study, 3,401 hypertensive patients (1,853 females and 1,548 males) aged ≥65 years treated simultaneously with statins, antiplatelet agents and ACEIs/ARBs and in whom PAD was newly diagnosed during 2012 were analysed. A patient was classified as non-persistent when he/she was non-persistent with at least one of the three analysed medication classes. The most important characteristics associated with the probability of non-persistence were identified using the Cox regression. RESULTS: At the end of the follow-up period (mean length 1.8 years), 1,869 (55.0%) patients (including 1,090 females and 779 males) were classified as non-persistent. In the whole study cohort, factors associated with non-persistence were female sex, atrial fibrillation, and being a new user of at least one of the analysed medication classes; in males, they were university education, atrial fibrillation, and epilepsy, and, in females, being a new user. CONCLUSION: Identification of sex differences in factors associated with non-persistence makes it possible to determine the groups of patients in whom special attention should be paid to improving their persistence with a combination of medicines in order to ensure successful secondary prevention of PAD.

• Publication type
• Journal Article MeSH

Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer. It also summarizes the established molecules with FTO-inhibiting activity. Given the extensive impact of FTO on both physiology and pathophysiology, this overview provides illustrative insights into its roles, rather than an exhaustive account. A proper understanding of FTO function in human diseases could lead to new treatment approaches, potentially unlocking novel avenues for addressing both metabolic disorders and malignancies. The evolving insights into FTO's regulatory mechanisms hold great promise for future advancements in disease treatment and prevention.

• Publication type
• Journal Article MeSH
• Review MeSH

INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.

• MeSH
• Biomarkers blood   MeSH
• Cytokines blood   MeSH
• Adult MeSH
• Glucocorticoids * administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Inflammation Mediators * blood   metabolism   MeSH
• Arthritis, Rheumatoid * drug therapy   blood   immunology   MeSH
• Aged MeSH
• Inflammation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The increase in extreme climate events associated with global warming is a great menace to crop productivity nowadays. In addition to abiotic stresses, warmer conditions favor the spread of infectious diseases affecting plant performance. Within this context, beneficial microbes constitute a sustainable alternative for the mitigation of the effects of climate change on plant growth and productivity. Used as biostimulants to improve plant growth, they also increase plant resistance to abiotic and biotic stresses through the generation of a primed status in the plant, leading to a better and faster response to stress. In this review, we have focused on the importance of a balanced redox status for the adequate performance of the plant and revisited the different antioxidant mechanisms supporting the biocontrol effect of beneficial microbes through the adjustment of the levels of reactive oxygen species (ROS). In addition, the different tools for the analysis of antioxidant responses and redox regulation have been evaluated. The importance of redox regulation in the activation of the immune responses through different mechanisms, such as transcriptional regulation, retrograde signaling, and post-translational modification of proteins, emerges as an important research goal for understanding the biocontrol activity of the beneficial microbes.

• Publication type
• Journal Article MeSH
• Review MeSH

OBJECTIVE: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. METHODS: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis. RESULTS: The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score. LIMITATIONS: The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples. CONCLUSIONS: The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.

• MeSH
• Depressive Disorder, Treatment-Resistant * drug therapy   MeSH
• Depressive Disorder, Major drug therapy   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Hallucinogens * administration & dosage   pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Psilocybin * pharmacology   administration & dosage   MeSH
• Psychiatric Status Rating Scales MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH