https://hdl.handle.net/20.500.14178/906 Tue, 07 Apr 2026 16:20:34 GMT 2026-04-07T16:20:34Z https://hdl.handle.net/20.500.14178/3473 Assessing potentially inappropriate medication use among older adults in Central and Eastern Europe Brkić, Jovana; Reissigová, Jindra; Okuyan, Betül; Ortner Hadžiabdić, Maja; Marinković, Valentina; Somers, Annemie; Onder, Graziano; Šesto, Sofija; Altiparmak, Öznur; Kummer, Ingrid; Držaić, Margita; Fialová, Daniela Objective The aim of this study was to examine the prevalence of potentially inappropriate medication (PIM) use and its associated risk factors in community-dwelling older adults from five Central and Eastern European (CEE) countries. Materials and methods This secondary analysis of a cross-sectional survey, which was part of the Horizon 2020 EuroAgeism ESR7 project, was conducted between February 2019 and March 2020 in Bulgaria, Croatia, Czechia, Estonia, and Serbia. We enrolled older adults aged >= 65 years who visited community pharmacies to acquire medications. The prevalence of PIM use was determined by applying all 282 criteria from the EU(7)-PIM list. Risk and protective factors for PIM use were evaluated using multiple logistic regression. R software version 4.3.2 was used in statistical analysis. Results Most of the 2,155 participants were women (63.3%) and aged 65-74 years (64.8%). The overall PIM prevalence was 56.0% (95% confidence interval 53.8%-58.1%), ranging from 29.5% in Czechia to 70.0% in Croatia. The most commonly used PIMs were benzodiazepines (16.7% of all PIMs), followed by nonsteroidal anti-inflammatory drugs (14.3%), and proton pump inhibitors taken for more than 8 weeks (14.1%). Multiple logistic regression revealed that residence, increasing comorbidity burden, and polypharmacy were significant risk factors associated with PIM use in older adults. Conclusions Our findings demonstrate a high prevalence of PIM use among older patients from CEE countries and considerable cross-country differences, underscoring the need to improve medication prescribing for older adults to improve healthcare quality and patient outcomes. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3473 2025-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3472 Anticholinergic and Sedative Medication Burden in Croatian Older Adults: EuroAgeism Cohort Findings Držaić, Margita; Bužančić, Iva; Kummer, Ingrid; Bošković, Andrea; Glavaš, Dragan; Ortner Hadžiabdić, Maja; Brkić, Jovana; Fialová, Daniela Use of anticholinergic and sedative medications is potentially inappropriate in older adults due to associated adverse effects, including impaired cognitive and physical function. This study evaluated anticholinergic and sedative burden in Croatian community-dwelling older adults using the Drug Burden Index (DBI) and examined its association with self-reported health and healthcare utilization over 12 months. This observational, cross-sectional study, part of the EuroAgeism H2020 ESR 7 project, included conveniently sampled adults >= 65 years from community pharmacies in three Croatian regions. Data were collected using a standardized research questionnaire. DBI was used to quantify exposure to anticholinergic and sedative medications. Multivariate regression analyses examined associations between DBI and health outcomes, using logistic regression for binary outcomes and linear regression for self-reported health. Among 388 participants (63.7% female, median age 73), most had multimorbidity (median five diagnoses) and polypharmacy (63.9%), while 57% used at least one DBI medication - most commonly diazepam (15.5%) and tramadol (14.7%). High DBI (>= 1) independently predicted more emergency department (ED) visits (OR = 2.45) and worse self-rated health (B = -0.26), but not hospitalization. High DBI in older adults was associated with more ED visits and poorer self-rated health, highlighting the need for targeted interventions to reduce anticholinergic and sedative use in this vulnerable population. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3472 2025-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3455 Dynamic shifts in trophoblast nucleos(t)ide metabolism, transport, and adenosine signaling during gestation and preterm birth Ali, Mohammed; Adler, Mariia; Libra, Antonín; Vokřál, Ivan; Karahoda, Rona; Cífková, Eva; Lísa, Miroslav; Tomek, Jakub; Novotná, Magdaléna; Štaud, František; Červený, Lukáš Nucleos(t)ides are essential for DNA/RNA synthesis, energy metabolism, and signaling, yet their roles in placental development remain poorly understood. The placenta undergoes dynamic metabolic adaptations throughout gestation to support fetal growth. This study investigates gene expression shifts in nucleos(t)ide metabolism, transport, and adenosine signaling during placental development and in the pathological condition of spontaneous preterm birth (PTB). We analyzed gene expression in first-trimester (n = 10) and term (n = 10), and PTB (n = 10) human placentas, and in cytotrophoblast and syncytiotrophoblast stage in primary human trophoblasts (n = 3) and BeWo (n = 5) cells. For developmental context, rat placentas were examined at gestation days (GD) GD12, GD15, and GD20 (n = 5 per group) that correspond to early second trimester in the human placenta. We found that genes involved in nucleos(t)ide metabolism and adenosine signaling were dominantly upregulated from early gestation to term in the human placenta. PTB placentas revealed further elevation compared to the term placenta. Differentiation from cytotrophoblast to syncytiotrophoblast was accompanied by only minor changes. Pearson's correlation analysis revealed strong gene-metabolite and gene-gene associations, highlighting an integrated metabolic network regulating placental function. Gene expression also differed among the tested GDs in the rat placenta. These findings demonstrate dynamic changes of nucleos(t)ide metabolism during healthy placental development and enhanced expression in PTB placentas, suggesting increasing needs for nucleos(t)ides during placental growth and metabolic shifts in the PTB placenta. Our data also indicate that nucleos(t)ide metabolism is preserved in both proliferative and differentiated states. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3455 2025-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3452 Anticoronavirus Isoquinoline Alkaloids: Unraveling the Secrets of Their Structure-Activity Relationship Šafratová, Marcela; Chen, Yu-Li; Hošťálková, Anna; Chlebek, Jakub; Hsieh, Chung-Fan; Chen, Bing-Hung; Cahlíková, Lucie; Kosturko, Štefan; Backlund, Anders; Horng, Jim-Tong; Hwang, Tsong-Long; Kořínek, Michal Background: Natural alkaloids are a structurally diverse class of bioactive compounds with significant therapeutic potential. This study aimed to evaluate the in vitro antiviral activity of various natural alkaloids against coronaviruses, clarify molecular effects via bioassays and docking, and explore structure-activity relationships. Tested compounds included a wide variety of isoquinoline and Amaryllidaceae-type alkaloids. Methodology: Antiviral activity was assessed using HCoV-229E and pseudotyped lentivirus assays for different strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxicity was evaluated with the WST-1 assay. AutoDock was used for molecular docking, online tools assessed drug-likeness, and ChemGPS-NP analyzed physicochemical properties correlated to antiviral clinical drugs. Results: Several bis-benzylisoquinoline alkaloids, especially from Berberis vulgaris L., and specific Amaryllidaceae alkaloids showed protective activity against HCoV-229E (EC50 = 4.1-8.1 mu M). Active compounds were further tested against SARS-CoV-2 variants. Aromoline (Compound 16) exhibited strong antiviral activity, inhibiting D614G, Delta, and Omicron variants in pseudovirus assays with IC50 values of 0.47-0.66 mu M. Other bis-benzylisoquinoline analogues showed moderate activity (IC50 = 1.24-2.86 mu M). Docking studies revealed aromoline's favorable interaction at the SARS-CoV-2 spike/ACE2 interface, forming hydrogen bonds with Gln493 and Ser494 (binding energy -5.34 kcal/mol). ChemGPS-NP analysis highlighted a distinct cluster of active bis-benzylisoquinolines (Compounds 16-19) in chemical space. Conclusion: This study highlights the antiviral potential of bis-benzylisoquinoline and Amaryllidaceae alkaloids, particularly aromoline. The findings support their relevance as scaffolds for developing novel anticoronavirus agents and advance the understanding of their structure-activity relationships. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3452 2025-01-01T00:00:00Z