Úzkostné poruchy jsou v současnosti nejčetnější skupinou duševních poruch, postihují světově více než 300 milionů lidí. Rozpočty směřující na léčení a prevenci těchto poruch jsou velmi omezené. Článek se zaměřuje na soucit se sebou, který je dostupným přístupem snižování úzkostných příznaků i potenciálního léčení úzkostných poruch. Uvedený text se opírá zejména o teorii tří systémů regulace emocí, doplněnou o rešerši studií zaměřujících se na vztah mezi soucitem se sebou, úzkostnými příznaky, citovou vazbou a oxytocinem. Pro budoucí rozvoj tohoto oboru je zapotřebí více randomizovaných kontrolovaných longitudinálních studií a komplexnějších výzkumných modelů, zkoumajících zejména roli mediačních/moderačních faktorů, jako je citová vazba či emoční regulace. Autoři v oboru by také měli zvážit adaptování a validaci většího množství intervencí v rámci klinické populace. Významný potenciál budoucího výzkumu lze spatřit ve zkoumání role oxytocinu, který dle některých studií vykazuje příznivé efekty pro snižování úzkostí. V poslední části jsou prezentována doporučení pro podporu praxe pracovníků v oblasti duševního zdraví.

Anxiety disorders are currently the most common group of mental disorders, affecting more than 300 million people worldwide. Budgets for the treatment and prevention of these disorders are very limited. The article focuses on self-compassion, which is an available approach to reducing anxiety symptoms as well as potentially treating anxiety disorders. The above text is mainly based on the theory of three systems of emotion regulation, as well as studies focusing on the relationship between self-compassion, anxiety symptoms, emotional attachment and oxytocin. Based on this, recommendations for future studies are presented. For the future development of this field, more randomized controlled longitudinal studies and more complex research models are needed, especially investigating the role of mediating/moderating factors such as emotional attachment, personality characteristics or emotional regulation. Authors in the field should also consider adapting and validating more interventions within a clinical population. Significant potential for future research can be seen in examining the role of oxytocin, which according to some studies shows beneficial effects for reducing anxiety. In the last part, recommendations for supporting the practice of mental health workers are presented.

• MeSH
• lidé MeSH
• oxytocin fyziologie   MeSH
• psychoterapie MeSH
• soucit se sebou * MeSH
• úzkost psychologie   MeSH
• úzkostné poruchy * patologie   psychologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Parents' social comparison is a common phenomenon that occurs in China. It refers to the behavior of parents imagining other people's children as an excellent role model without shortcomings and comparing their own children with them. This behavior may affect their child's mood. The purpose of this study was to explore the impact of parents' social comparison on adolescents' self-esteem through the mediating role of upward social comparison, and to explore the moderating role of optimism in upward social comparison and self-esteem. Parents' social comparison questionnaire, upward social comparison questionnaire, self-esteem questionnaire and life orientation questionnaire were distributed through online questionnaires, and 576 valid questionnaires were received. The results of the study found that upward social comparison plays a partial mediating role in the negative impact of parents' social comparison on self-esteem, and optimism plays a moderating role in the impact of upward social comparison on self-esteem. This study illustrates the harmful effects of parents' social comparison on adolescent mental health, but this harm can be mitigated through the teaching of optimism. This study shows that parents' social comparison is not advisable, and attention should be paid to maintaining the optimistic attitude of teenagers to ensure their healthy growth.

• Publikační typ
• časopisecké články MeSH

Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin-3'-O-sulfate (M3'S), AMP, and ampelopsin-4'-O-sulfate (A4'S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion-transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3'S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3'S, AMP, and A4'S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3'S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3'S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR-containing dietary supplements may affect the OATP-mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3'S.

• MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• cytochrom P450 CYP2C9 metabolismus   MeSH
• flavonoidy * farmakologie   MeSH
• flavonoly farmakologie   MeSH
• lidé MeSH
• polypeptid C přenášející organické anionty * metabolismus   MeSH
• přenašeče organických aniontů * metabolismus   MeSH
• sérový albumin metabolismus   MeSH
• sírany metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Physiology-based pharmacokinetic modeling suggests that rifabutin can out-balance P-glycoprotein (P-gp) induction by concurrent P-gp inhibition. However, clinical or experimental evidence for this Janus-faced rifabutin effect is missing. Consequently, LS180 cells were exposed to a moderately (2 μM) and strongly (10 μM) P-gp-inducing concentration of rifampicin or rifabutin for 6 days. Cellular accumulation of the fluorescent P-gp substrate rhodamine 123 was evaluated using flow cytometry, either without (induction only) or with adding rifamycin drug to the cells during the rhodamine 123 efflux phase (induction + potential inhibition). Rhodamine 123 accumulation was decreased similarly by both drugs after 6-day exposure (2 μM: 55% residual fluorescence compared to non-induced cells, P < 0.01; 10 μM: 30% residual fluorescence compared to non-induced cells, P < 0.001), indicating P-gp induction. Rhodamine 123 influx transporters mRNA expressions were not affected, excluding off-target effects. Acute re-exposure to rifabutin, however, considerably re-increased rhodamine 123 accumulation (2 μM induction: re-increase by 55%, P < 0.01; 10 μM induction: 49% re-increase, P < 0.001), suggesting P-gp inhibition. In contrast, rifampicin only had weak effects (2 μM induction: no re-increase; 10 μM induction: 16% re-increase; P < 0.05). Molecular docking analysis eventually revealed that rifabutin has a higher binding affinity to the inhibitor binding site of P-gp than rifampicin (ΔG (kcal/mol) = -11.5 vs -5.3). Together, this study demonstrates that rifabutin can at least partly mask P-gp induction by P-gp inhibition, mediated by high affinity binding to the inhibitory site of P-gp.

• MeSH
• P-glykoprotein metabolismus   MeSH
• rhodamin 123 metabolismus   MeSH
• rifabutin * farmakologie   MeSH
• rifampin * farmakologie   MeSH
• simulace molekulového dockingu MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Health literacy is a core public health issue in relation to children and adolescents associated with multiple health behaviours and health outcomes. The aim of the study is to test the direct associations between health literacy, physical activity behaviour, health outcomes of body composition and cardiorespiratory fitness among Slovak adolescents and possible indirect effect of health literacy on health outcomes of body composition and cardiorespiratory fitness mediated by adolescents' physical activity behaviour. METHODS: Data from the Slovak Health Behaviour in School-aged Children (HBSC) study conducted in 2022 were used. For the purposes of this study, a subsample of the adolescents (n = 508; mean age = 14.50; SD = 0.82; 54.3% boys) which provided HBSC questionnaire data on health literacy, moderate-to-vigorous physical activity and vigorous physical activity and participated in body composition (InBody 230) and cardiorespiratory fitness (20-m shuttle run test) measurements. Data were analysed using linear regression analysis. RESULTS: The findings showed that higher health literacy of the adolescents was directly associated with higher frequency of physical activity represented by moderate-to-vigorous physical activity and vigorous physical activity and only with the visceral fat area in the crude model. Furthermore, there was an indirect effect of health literacy on cardiorespiratory fitness and most of the body composition variables (except the Body Mass Index) which was mediated by physical activity of the respondents. CONCLUSIONS: Health literacy is indirectly associated to body composition and cardiorespiratory fitness through higher frequency of physical activity. It seems that health literacy as cognitive and social competencies need behavioural components to be involved in the proposed causal pathway between health literacy and health outcomes. Our findings may contribute to the process of creating a framework for future health literacy interventions in adolescents.

• MeSH
• cvičení * fyziologie   MeSH
• kardiorespirační zdatnost * fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• průzkumy a dotazníky MeSH
• složení těla * MeSH
• zdravotní gramotnost * statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

• MeSH
• autoprotilátky * krev   imunologie   MeSH
• dermatomyozitida imunologie   krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• myozitida * imunologie   krev   MeSH
• progrese nemoci MeSH
• registrace * MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester 4n, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for 4n) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound 4n also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible toxicity on nontumor normal human dermal fibroblasts. Compound 4n represents an important complementary pharmacological tool to study the involvement of adrenoceptor subtypes in pathophysiologic conditions such as inflammation and sepsis and a novel candidate for further preclinical development to treat ADRA2A-mediated pathologies.

• MeSH
• alfa-2-adrenergní receptory - antagonisté * farmakologie   chemie   chemická syntéza   MeSH
• alfa-2-adrenergní receptory * metabolismus   MeSH
• lidé MeSH
• racionální návrh léčiv * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• yohimbin * farmakologie   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This study aimed to explore the effect of socioeconomic disadvantage accumulated in marginalised Roma communities (MRCs) on early childhood development and to assess the role of selected socioeconomic indicators in the association between belonging to MRCs vs. the majority and early childhood development. We obtained cross-sectional data from 232 mother-child dyads from MRCs and the majority population. The differences in early childhood development and background variables between the two groups were tested using chi-square and Mann-Whitney U tests. The moderated mediation was tested using PROCESS Macro in SPSS Model 14 on 5000 bootstrap samples. Statistically significant differences between children from MRCs and the majority were found in terms of maternal age, parental education, household equipment, as well as early childhood development. Household equipment moderated the indirect effect of being from MRCs vs. the majority on early childhood development through parental education. The indirect effect through parental education was high at a low household equipment level, reduced at an average level and non-significant at a high level of household equipment. Our study uncovered disparities in early childhood development between children from MRCs and the majority population. Parental education significantly influenced developmental outcomes, while household equipment mitigated its impact.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP+) to preferentially target cancer cell's mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia. METHODS: B16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system. RESULTS: Hypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors. CONCLUSIONS: We successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy.

• Publikační typ
• časopisecké články MeSH

Cílem přehledové práce je zmapovat, jak se rodiče podílejí na vzniku a vývoji online závislostí. V textu je pozornost zaměřena na vztahy v rodině, vztahy mezi rodiči a dospívajícími, výchovné styly rodičů, rodičovskou mediaci a vzorce užívání informačních technologií rodiči. Výsledky docházejí opakovaně k závěrům, že důležitým protektivním faktorem ve vývoji online závislostí u adolescentů je kvalita vztahu s rodiči a rodinného prostředí, ve kterém vyrůstají. Pozitivní vztahy, otevřená komunikace, respektování autonomie dospívajícího a emoční blízkost jsou prevencí online závislostí. V rámci rodičovských výchovných stylů se ukazuje důležitá rodičovská vřelost a střední míra kontroly. Techniky rodičovské mediace korelující s nižším výskytem online závislostí jsou společné užívání informačních technologií a aktivní mediace, tedy techniky, které respektují autonomii dospívajícího. Rodiče a odborníci by měli věnovat významnou pozornost také vzorcům užívání informačních technologií samotných rodičů, kteří fungují jako důležitý model ve vztahu k informačním technologiím.

The aim of this review is to explore parents’ involvement in the onset and development of online addictions among adolescents. The text focuses on family relationships, relationships between parents and teenagers, parenting styles, parental mediation, and patterns of parents’ use of information technology. The findings are consistent in showing that the quality of adolescents’ relationships with their parents and the family environment are important protective factors for the development of online addiction among adolescents. Factors which prevent online addiction include positive relationships, open communication, respect for the adolescent’s autonomy, and emotional closeness. Regarding parenting styles, parental warmth and a moderate degree of control are shown to be important. Parental mediation techniques associated with the lower incidence of online addictions include co-use of information technology and active mediation, i.e. techniques that respect the adolescent’s autonomy. Parents and professionals should also pay significant attention to the patterns of information technology use on the part of the parents, as these are an important model for adolescents in terms of the use of information technology.