Hydrogen sulfide (H2S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H2S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine. According to our measurements made with an H2S-specific sensor, nucleoside dithioacetates are moderately fast H2S donors, the guanosine derivative showed the fastest kinetics and the adenosine derivative the slowest. The antioxidant activity of 5'-thionucleosides is significantly higher than that of trolox, but lower than that of ascorbic acid, while intact dithioacetates have no remarkable antioxidant effect. In human Calu cells, the guanosine derivative showed a moderate anti-SARS-CoV-2 effect which was also confirmed by virus yield reduction assay. Dithioacetyl-adenosine and its metabolite showed similar acute cardiac effects as adenosine, however, it is noteworthy that both 5'-thio modified adenosines increased left ventricular ejection fraction or stroke volume, which was not observed with native adenosine.

• MeSH
• adenosin analogy a deriváty   MeSH
• antioxidancia * farmakologie   chemie   MeSH
• antivirové látky * farmakologie   chemická syntéza   chemie   MeSH
• buněčné linie MeSH
• farmakoterapie COVID-19 MeSH
• lidé MeSH
• nukleosidy farmakologie   chemie   metabolismus   MeSH
• SARS-CoV-2 účinky léků   metabolismus   MeSH
• sulfan * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions. Multi-group confirmatory factor analysis indicated that configural and metric invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional SWLS model has universal applicability. Full scalar invariance was achieved across gender identities and age groups. Based on alignment optimisation methods, partial scalar invariance was achieved across all but three national groups and across all languages represented in the BINS. There were large differences in latent SWLS means across nations and languages, but negligible-to-small differences across gender identities and age groups. Across nations, greater life satisfaction was significantly associated with greater financial security and being in a committed relationship or married. The results of this study suggest that the SWLS largely assesses a common unidimensional construct of life satisfaction irrespective of respondent characteristics (i.e., national group, gender identities, and age group) or survey presentation (i.e., survey language). This has important implications for the assessment of life satisfaction across nations and provides information that will be useful for practitioners aiming to promote subjective well-being internationally.

• MeSH
• dospělí MeSH
• faktorová analýza statistická MeSH
• genderová identita * MeSH
• jazyk (prostředek komunikace) MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• osobní uspokojení * MeSH
• průzkumy a dotazníky MeSH
• psychometrie metody   MeSH
• senioři MeSH
• věkové faktory MeSH
• zpráva o sobě MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock. The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.

• MeSH
• dospělí MeSH
• epigeneze genetická * MeSH
• genetická variace MeSH
• lidé MeSH
• longitudinální studie MeSH
• mitochondriální DNA * genetika   MeSH
• mladý dospělý MeSH
• předčasné stárnutí genetika   MeSH
• stárnutí * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

• MeSH
• gastrointestinální krvácení * prevence a kontrola   MeSH
• gastrointestinální látky terapeutické užití   MeSH
• jednotky intenzivní péče * MeSH
• lidé MeSH
• síťová metaanalýza * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

The vertebrate visual cycle hinges on enzymatically converting all-trans-retinol (at-ROL) into 11-cis-retinal (11c-RAL), the chromophore that binds to opsins in photoreceptors, forming light-responsive pigments. When struck by a photon, these pigments activate the phototransduction pathway and initiate the process of vision. The enzymatic isomerization of at-ROL, crucial for restoring the visual pigments and preparing them to receive new light stimuli, relies on various enzymes found in both the photoreceptors and retinal pigment epithelium cells. To function effectively, retinoids must shuttle between these two cell types. Retinol-binding protein 3 (RBP3), located in the interphotoreceptor matrix, probably plays a pivotal role in this transport mechanism. Comprised of four retinoid-binding modules, RBP3 also binds fatty acids, potentially aiding retinal function by facilitating the loading and unloading of different retinoids at specific cell types thereby directing the cycle. In this study, we present a 3.67 Å cryoEM structure of porcine RBP3, along with molecular docking analysis and corroborative in-solution small-angle X-ray scattering data for titration of RBP3 with relevant ligands, that also give insights on RBP3 conformational adaptability.

• MeSH
• difrakce rentgenového záření MeSH
• elektronová kryomikroskopie metody   MeSH
• konformace proteinů MeSH
• maloúhlový rozptyl * MeSH
• molekulární modely MeSH
• oční proteiny MeSH
• prasata MeSH
• proteiny vázající retinol * chemie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vitamin A metabolismus   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Due to the limited effectiveness of pharmacological treatment, there is a growing need to explore non-pharmacological psychosocial interventions such as music therapy when treating the behavioural and psychological symptoms of dementia (BPSD). METHOD: We randomised 57 nursing home residents into individual active music therapy plus standard care (aMT), individual receptive music therapy with tactile sound vibration plus standard care (rMT), or the standard care control group (CG). A trained music therapist provided 12 sessions over 6 weeks. The outcomes (BPSD; depression; quality of life; medical system usage; activities of daily living; music therapy engagement) were measured at baseline (0 week), post-intervention (6 weeks), and follow-up (12 weeks). RESULTS: The results indicated small beneficial effects for BPSD in aMT and rMT at follow-up, a small beneficial effect for total musical engagement in aMT and rMT, a small negative effect for verbal communication in rMT, and a small beneficial effect for medical usage in the CG. CONCLUSION: Both aMT and rMT methods showed promise for managing BPSD and increasing engagement during music therapy. rMT may be more suited for advanced stages of dementia. Future studies should evaluate the appropriateness and effectiveness of each intervention according to disease severity.

• MeSH
• činnosti denního života MeSH
• demence * terapie   psychologie   MeSH
• deprese terapie   MeSH
• kvalita života MeSH
• lidé MeSH
• muzikoterapie * metody   MeSH
• pečovatelské domovy MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pragmatická klinická studie MeSH
• randomizované kontrolované studie MeSH

In response to a recent case report published in the International Journal of Legal Medicine entitled "A case of hemorrhage at the junctions of the posterior intercostal arteries-a vital sign?", we wish to corroborate the findings of periadventitial hemorrhages at the junctions of the posterior intercostal arteries in cases of suicidal hanging and to reveal two other novel aortic lesions associated with hanging. In our ongoing prospective study, we identified six cases of aortic intimal ruptures among 257 suicidal hanging deaths, along with the novel observation of subintimal hemorrhages-both of which have not been previously documented in the forensic literature. Our findings suggest that the complex anatomy of the aorta and surrounding structures may increase the vulnerability of vascular structures during hanging, particularly under conditions of complete suspension. We propose that reported aortic lesions may serve as significant morphological indicators of hanging, thereby enriching its medicolegal investigation. To establish the diagnostic relevance of these findings, further prospective autopsy studies with larger sample sizes are warranted.

• MeSH
• aorta * patologie   zranění   MeSH
• asfyxie * patologie   MeSH
• dokonaná sebevražda * MeSH
• dospělí MeSH
• krvácení * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• poranění krku * patologie   MeSH
• prospektivní studie MeSH
• ruptura aorty * patologie   MeSH
• senioři MeSH
• soudní patologie MeSH
• tunica intima patologie   zranění   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH

Limited availability constrains the implementation of 225Ac, the most promising α emitter for targeted therapy, in clinical practice. Proton activation of 226Ra is one of few realistic solutions to this problem. We have therefore measured cross sections of relevant 226Ra(p,xn) nuclear reactions in the energy range of 12.0 to 17.2 MeV. The obtained results allowed us to deduce the yield of 224Ac, 225Ac, and 226Ac. The consequences of our data to predictions of production capacity and radionuclidic purity of 225Ac are thoroughly discussed, and their comparison with previous measurements and with the prediction of the TALYS 1.96 nuclear reaction model code run with default parameters are provided.

• MeSH
• aktinium * chemie   MeSH
• fosfor * chemie   MeSH
• radiochemie MeSH
• radium * chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Magnetic resonance spectroscopic imaging (MRSI) enables the simultaneous noninvasive acquisition of MR spectra from multiple spatial locations inside the brain. Although 1H-MRSI is increasingly used in the human brain, it is not yet widely applied in the preclinical setting, mostly because of difficulties specifically related to very small nominal voxel size in the rat brain and low concentration of brain metabolites, resulting in low signal-to-noise ratio (SNR). In this context, we implemented a free induction decay 1H-MRSI sequence (1H-FID-MRSI) in the rat brain at 14.1 T. We combined the advantages of 1H-FID-MRSI with the ultra-high magnetic field to achieve higher SNR, coverage, and spatial resolution in the rat brain and developed a custom dedicated processing pipeline with a graphical user interface for Bruker 1H-FID-MRSI: MRS4Brain toolbox. LCModel fit, using the simulated metabolite basis set and in vivo measured MM, provided reliable fits for the data at acquisition delays of 1.30 ms. The resulting Cramér-Rao lower bounds were sufficiently low (< 30%) for eight metabolites of interest (total creatine, N-acetylaspartate, N-acetylaspartate + N-acetylaspartylglutamate, total choline, glutamine, glutamate, myo-inositol, and taurine), leading to highly reproducible metabolic maps. Similar spectral quality and metabolic maps were obtained with one and two averages, with slightly better contrast and brain coverage due to increased SNR in the latter case. Furthermore, the obtained metabolic maps were accurate enough to confirm the previously known brain regional distribution of some metabolites. The acquisitions proved high reproducibility over time. We demonstrated that the increased SNR and spectral resolution at 14.1 T can be translated into high spatial resolution in 1H-FID-MRSI of the rat brain in 13 min using the sequence and processing pipeline described herein. High-resolution 1H-FID-MRSI at 14.1 T provided robust, reproducible, and high-quality metabolic mapping of brain metabolites with minimal technical limitations.

• MeSH
• krysa rodu rattus MeSH
• magnetická rezonanční tomografie metody   MeSH
• metabolom MeSH
• mozek * metabolismus   diagnostické zobrazování   MeSH
• poměr signál - šum MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• protonová magnetická rezonanční spektroskopie metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

To trace evolution of Panton-Valentine leucocidin-positive clonal complex 398 methicillin-resistant Staphylococcus aureus (MRSA) in the Czech Republic, we tested 103 MRSA isolates from humans. Five (4.9%) were Panton-Valentine leucocidin-positive clonal complex 398, sequence types 1232 and 9181. Spread to the Czech Republic may result from travel to or from other countries.

• MeSH
• bakteriální toxiny * biosyntéza   genetika   MeSH
• dějiny 21. století MeSH
• dospělí MeSH
• exotoxiny * genetika   biosyntéza   MeSH
• leukocidiny * genetika   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus * genetika   izolace a purifikace   MeSH
• stafylokokové infekce * mikrobiologie   epidemiologie   MeSH
• Check Tag
• dějiny 21. století MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• Geografické názvy
• Česká republika MeSH