Publikace obsahuje úplné znění aktuálních českých zákonů a vyhlášek, které se týkají sociálního zabezpečení. Určeno odborné veřejnosti.

• MeSH
• sociální péče zákonodárství a právo   MeSH
• sociální práce zákonodárství a právo   MeSH
• sociální zabezpečení zákonodárství a právo   MeSH
• Geografické názvy
• Česká republika MeSH
• Ukrajina MeSH

• Konspekt
• Sociální problémy vyžadující podporu a pomoc. Sociální zabezpečení
• NLK Obory
• právo, zákonodárství
• sociologie
• ekonomie, ekonomika, ekonomika zdravotnictví
• NLK Publikační typ
• zákony
• právní předpisy

Proper fetal development requires tight regulation of serotonin concentrations within the fetoplacental unit. This homeostasis is partly maintained by the placental transporter OCT3/SLC22A3, which takes up serotonin from the fetal circulation. Metformin, an antidiabetic drug commonly used to treat gestational diabetes mellitus, was shown to inhibit OCT3. We, therefore, hypothesized that its use during pregnancy could disrupt placental serotonin homeostasis. This hypothesis was tested using three experimental model systems: primary trophoblast cells isolated from the human term placenta, fresh villous human term placenta fragments, and rat term placenta perfusions. Inhibition of serotonin transport by metformin at three concentrations (1 μM, 10 μM, and 100 μM) was assessed in all three models. The OCT3 inhibitor decynium-22 (100 μM) and paroxetine (100 μM), a dual inhibitor of SERT and OCT3, were used as controls. In primary trophoblasts, paroxetine exhibited the strongest inhibition of serotonin uptake, followed by decynium-22. Metformin showed a concentration-dependent effect, reducing serotonin uptake by up to 57 % at the highest concentration. Its inhibitory effect was less pronounced in fresh villous fragments but remained statistically significant at all concentrations. In the perfused rat placenta, metformin demonstrated a concentration-dependent effect, reducing placental serotonin uptake by 44 % at the highest concentration tested. Our findings across all experimental models show inhibition of placental OCT3 by metformin, resulting in reduced serotonin uptake by the trophoblast. This sheds light on mechanisms that may underpin metformin-mediated effects on fetal development.

• MeSH
• biologický transport účinky léků   MeSH
• hypoglykemika farmakologie   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• metformin * farmakologie   MeSH
• oktamerní transkripční faktor 3 metabolismus   MeSH
• placenta * metabolismus   účinky léků   MeSH
• potkani Wistar MeSH
• proteiny přenášející organické kationty MeSH
• serotonin * metabolismus   MeSH
• těhotenství MeSH
• trofoblasty * metabolismus   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• kardiologie * MeSH
• lidé MeSH
• periodika jako téma * normy   MeSH
• šíření informací MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• společnosti lékařské * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Persons living in industrial environments are exposed to levels of air pollution that can affect their health and fertility. The Czech capital city, Prague, and the Ostrava industrial agglomeration differ in their major sources of air pollution. In Prague, heavy traffic produces high levels of nitrogen oxides throughout the year. In the Ostrava region, an iron industry and local heating are sources of particulate matter (PM) and benzo[a]pyrene (B[a]P), especially in the winter. We evaluated the effects of air pollution on human sperm mitochondrial DNA (mtDNA). Using real-time PCR, we analysed sperm mtDNA copy number and deletion rate in Prague city policemen in two seasons (spring and autumn) and compared the results with those from Ostrava. In Prague, the sperm mtDNA deletion rate was significantly higher in autumn than in spring, which is the opposite of the results from Ostrava. The sperm mtDNA copy number did not show any seasonal differences in either of the cities; it was correlated negatively with sperm concentration, motility, and viability, and with sperm chromatin integrity (assessed with the Sperm Chromatin Structure Assay). The comparison between the two cities showed that the sperm mtDNA deletion rate in spring and the sperm mtDNA copy number in autumn were significantly lower in Prague vs. Ostrava. Our study supports the hypothesis that sperm mtDNA deletion rate is affected by the composition of air pollution. Sperm mtDNA abundance is closely associated with chromatin damage and standard semen characteristics.

• MeSH
• dospělí MeSH
• látky znečišťující vzduch toxicita   škodlivé účinky   MeSH
• lidé MeSH
• mitochondriální DNA * genetika   MeSH
• motilita spermií účinky léků   MeSH
• pevné částice toxicita   škodlivé účinky   MeSH
• policie MeSH
• roční období MeSH
• spermie * účinky léků   MeSH
• variabilita počtu kopií segmentů DNA * MeSH
• znečištění ovzduší * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.

• MeSH
• androgeny * krev   metabolismus   MeSH
• benzhydrylové sloučeniny krev   MeSH
• cytokiny krev   metabolismus   MeSH
• dospělí MeSH
• endokrinní disruptory * krev   MeSH
• fenoly MeSH
• hirzutismus * krev   etiologie   chemicky indukované   MeSH
• hyperandrogenismus krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• obezita krev   metabolismus   MeSH
• syndrom polycystických ovarií * krev   metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer's disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ42 anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ42 complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ42 production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ42.

• MeSH
• Alzheimerova nemoc * metabolismus   patologie   etiologie   MeSH
• amyloidní beta-protein * metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• fosforylace MeSH
• lidé MeSH
• peptidové fragmenty metabolismus   MeSH
• protein 1 související s LDL-receptory * metabolismus   MeSH
• proteiny tau * metabolismus   MeSH
• tauopatie * metabolismus   patologie   etiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that, through its manipulation of endogenous oscillations, can affect cognition in healthy adults. Given the fact that both endogenous oscillations and cognition are impaired in various psychiatric diagnoses, tACS might represent a suitable intervention. We conducted a search of Pubmed and Web of Science databases and reviewed 27 studies where tACS is used in psychiatric diagnoses and cognition change is evaluated. TACS is a safe and well-tolerated intervention method, suitable for multiple-sessions protocols. It can be administered at home, individualized according to the patient''s anatomical and functional characteristics, or used as a marker of disease progression. The results are varying across diagnoses and applied protocols, with some protocols showing a long-term effect. However, the overall number of studies is small with a great variety of diagnoses and tACS parameters, such as electrode montage or used frequency. Precise mechanisms of tACS interaction with pathophysiological processes are only partially described and need further research. Currently, tACS seems to be a feasible method to alleviate cognitive impairment in psychiatric patients; however, a more robust confirmation of efficacy of potential protocols is needed to introduce it into clinical practise.

• MeSH
• duševní poruchy * terapie   patofyziologie   MeSH
• kognitivní dysfunkce * patofyziologie   etiologie   terapie   MeSH
• lidé MeSH
• přímá transkraniální stimulace mozku * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Metastatic renal cell carcinoma (mRCC) carrying sarcomatoid features (sRCC) has aggressive biology and poor prognosis. First-line immunotherapy (IO)-based combinations have improved the outcome of clear cell RCC patients, including that of sRCC. Real-world data confirming the adequate first-line management of sRCC is largely lacking. We investigated the clinical features and the outcome of sRCC patients treated with IO-based combinations within the ARON-1 study population (NCT05287464). The primary objective was to define the incidence and baseline clinical characteristics of sRCC compared with non-sRCC patients. The secondary objective was to describe the outcome of sRCC patients based on type of first-line treatment (IO + IO vs. IO + tyrosin kinase inhibitor [TKI]). We identified 1362 mRCC patients with IMDC intermediate or poor risk, 226 sRCC and 1136 non-sRCC. These two subgroups did not differ in terms of baseline characteristics. The median overall survival (OS) was 26.8 months (95%CI 21.6-44.2) in sRCC and 35.3 months (95%CI 30.2-40.4) in non-sRCC patients (p = .013). The median progression-free survival (PFS) was longer in non-sRCC patients compared to sRCC (14.5 vs. 12.3 months, p = .064). In patients treated with first-line IO + TKI the median OS was 34.4 months compared to 26.4 months of those who received IO + IO (p = .729). The median PFS was 12.4 months with IO + TKI and 12.3 months with IO + IO (p = .606). In conclusion, we confirm that sRCC are aggressive tumors with poor prognosis. IO-based combinations improve survival outcomes of sRCC patients, regardless from the type of strategy (IO + IO versus IO + TKI) adopted.

• MeSH
• dospělí MeSH
• imunoterapie metody   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• karcinom z renálních buněk * patologie   farmakoterapie   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * patologie   farmakoterapie   imunologie   mortalita   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

• MeSH
• dítě MeSH
• elektrokardiografie * MeSH
• hypertrofická kardiomyopatie * diagnóza   patofyziologie   komplikace   MeSH
• hypertrofie levé komory srdeční * diagnóza   patofyziologie   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: There is a lack of data on the long-term effect of nintedanib on survival in specific groups of idiopathic pulmonary fibrosis (IPF) patients with different phenotypes. We investigated the outcomes of nintedanib therapy in an observational study of a large multicentre real-world cohort of IPF patients with various initial characteristics. METHODS: The analysis included IPF patients treated with nintedanib (NIN) and IPF patients not receiving antifibrotic treatment (NAF) enrolled for the EMPIRE registry in 2015-2020. The patients were stratified according to their initial FVC predicted, dyspnoea, UIP pattern and age. All-cause mortality and annual rate of FVC decline were the main endpoints. Cox proportional hazards model for survival assessment and linear mixed-effects model for FVC decline modelling were used. RESULTS: A total of 869 NIN patients and 691 NAF patients were eligible for the analysis. The annual FVC decline rate was significantly different (adjusted values -0.053 l/yr vs -0.122 l/yr; p = 0.001). The adjusted hazard ratio (HR) for mortality was 0.40 (95 % CI 0.3 to 0.53, p < 0.001). The most significant effect of nintedanib was demonstrated in patients with impaired lung function, i.e., with an FVC predicted to be less than 80 % and a NYHA II to IV. Nintedanib therapy also reduced the difference in survival between men and women. CONCLUSIONS: Modelling confirmed that NIN therapy reduced differences in OS between patients with better and worse initial conditions and prognosis. Our results indicate that NIN is particularly beneficial for patients with advanced IPF and more severe phenotypes. TRIAL REGISTRATION: EMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on December 8, 2014.

• MeSH
• antifibrotické látky terapeutické užití   MeSH
• časové faktory MeSH
• fenotyp MeSH
• idiopatická plicní fibróza * farmakoterapie   mortalita   patofyziologie   MeSH
• indoly * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH