Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus that invades the central nervous system, leading to severe neurological manifestations. In this study, we developed a reporter virus comprising TurboGFP-expressing TBEV (tGFP-TBEV) as a versatile tool for advancing TBEV research. The tGFP-TBEV facilitates quantitative measurement of viral replication, enables precise tracking of individual infected cells, and supports high-throughput screening of potential antiviral compounds and virus-neutralization assays. Furthermore, tGFP-TBEV proved effective as a model for studying TBEV infection in rat organotypic cerebellar slices cultured ex vivo and for visualizing TBEV infection in the mouse brain. Using tissue-clearing protocols and light-sheet fluorescence microscopy, we achieved high-resolution, three-dimensional mapping of the TBEV distribution in the mouse brain. This analysis uncovered distinct patterns of TBEV tropism, with infections concentrated in regions associated with neurogenesis, olfactory processing, and specific neuroanatomical pathways. The ability to visualize infection at both the cellular and whole-organ level provides a new tool for detailed investigations into viral tropism, replication, and interactions with host tissues, paving the way for deeper insights into TBEV biology and the pathogenesis of tick-borne encephalitis.

• Klíčová slova
• TBEV, light-sheet microscopy, neurotropism, organotypic cerebellar slices, reporter viruses, tissue clearing,
• MeSH
• klíšťová encefalitida * virologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• luminescentní proteiny genetika   metabolismus   MeSH
• mozek * virologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• replikace viru MeSH
• reportérové geny MeSH
• tropismus virů MeSH
• viry klíšťové encefalitidy * genetika   fyziologie   MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• luminescentní proteiny MeSH

Vaccine hesitancy remains a significant public health challenge, particularly during pandemics when high immunization rates are crucial. While individual psychological antecedents of vaccine hesitancy have been extensively studied, limited empirical evidence exists on how contextual determinants, such as socioeconomic status, political trust, and digital literacy, collectively shape vaccine-related behaviors, particularly in Central European populations. This study explores the key determinants of COVID-19 vaccine hesitancy among Czech adults. A cross-sectional study was conducted using data from the 48th wave of the Czech national panel survey Život během pandemie [Life During Pandemic], carried out in March 2023. The data were obtained via an online questionnaire administered to a nationally representative sample of Czech adults (n = 1,708). Sociodemographic, socioeconomic, and anamnestic variables were examined alongside political attitudes. Psychological antecedents of vaccination were assessed using the 5C model (confidence, complacency, constraints, risk calculation, and collective responsibility), and digital vaccine literacy was measured using seven items covering trust in official sources, trust in social media, and the ability to evaluate and apply vaccine information. Statistical analyses included bivariate tests and multivariable regression models to identify vaccine uptake and intent determinants. Higher trust in constitutional institutions, including the president (OR = 1.55; 95/ CI: 1.38-1.74), government (1.60; 1.38-1.85), Chamber of Deputies (1.73; 1.48-2.02), and Senate (1.47; 1.29-1.69), was significantly associated with higher vaccine uptake. Similarly, positive attitudes toward the integration of Ukrainian refugees into Czech society - across domains such as work (1.63; 1.39-1.90), housing (1.59; 1.36-1.86), school (1.64; 1.41-1.92), language (1.57; 1.34-1.84), and culture (1.74; 1.50-2.03) - were positively associated with uptake. Greater confidence in vaccine safety and effectiveness was also a significant predictor (1.51; 1.44-1.58). In contrast, lower education (0.64; 0.56-0.73), lower income (0.91; 0.86-0.95), female sex (0.60; 0.47-0.76), and higher complacency (0.76; 0.73-0.80) were associated with reduced uptake. Respondents with better digital vaccine literacy, particularly those more adept at identifying misinformation, showed significantly greater vaccine confidence (mean score: 3.62 vs. 3.30, p < .001). Beyond psychological antecedents, institutional trust, political orientation, and digital vaccine literacy significantly shape COVID-19 vaccination behaviors. These findings underscore the importance of targeted interventions that address political and digital influences on vaccine hesitancy, and they highlight the need for future research to examine the causal pathways and longitudinal dynamics underlying these associations, particularly within Central and Eastern European contexts.

• Klíčová slova
• COVID-19, Czech Republic, refugees, social determinants of health, vaccination hesitancy,
• MeSH
• COVID-19 * prevence a kontrola   psychologie   MeSH
• dospělí MeSH
• důvěra * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odkládání očkování * psychologie   statistika a číselné údaje   MeSH
• politika MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• sociální média MeSH
• socioekonomické faktory MeSH
• vakcinace * psychologie   MeSH
• vakcíny proti COVID-19 * aplikace a dávkování   MeSH
• zdravotní gramotnost * 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
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• vakcíny proti COVID-19 * MeSH

ABSTRACTBackground: European health care workers recently experienced serious challenges to their mental health. Following the extremely stressful experience of the COVID-19 pandemic, the war in Ukraine caused a humanitarian influx of refugees in need of social and healthcare. We aimed to explore: (1) how working with refugees has affected the mental well-being of health care workers in the context of the COVID-19 pandemic, and (2) the nature of health care workers' emotional strain related to the refugee situation and the war in Ukraine.Methods: We used a combination of quantitative regression analyses and qualitative content analysis to assess data collected by an online questionnaire in 2022. The study included 1121 health care workers from the Czech arm of the international HEROES Study.Results: Quantitative findings did not indicate that working with Ukrainian refugees was reliably associated with a greater occurrence of symptoms of depression, anxiety, distress, or burnout. Qualitative analysis revealed five categories of emotional strain: impacts on working conditions, emotional reactions to refugees and the war, comparisons with the COVID-19 pandemic, and coping strategies.Conclusions: This study highlights the resilience of health care workers but also points to the need for ongoing support to address the complex emotional challenges they face during health crises.

Although we did not find a significant association between working with refugees and mental health issues, health professionals encountered emotionally challenging situations.Emotionally challenging situations involved reactions to the war and refugees, worsening working conditions, and higher subjective strain than during the COVID-19 pandemic.When comparing health workers caring for with refugees and COVID-19 patients, we found differences in their mental health issues.

• Klíčová slova
• COVID-19 pandemic, Migración, Migration, Russian-Ukrainian war, emotional strain, guerra ruso-ucraniana, malestar psicológico, pandemia de COVID-19, psychological distress,
• MeSH
• adaptace psychologická MeSH
• COVID-19 * psychologie   epidemiologie   MeSH
• deprese psychologie   epidemiologie   MeSH
• dospělí MeSH
• duševní zdraví * MeSH
• lidé středního věku MeSH
• lidé MeSH
• pandemie MeSH
• profesionální vyhoření * psychologie   epidemiologie   MeSH
• průzkumy a dotazníky MeSH
• psychický stres * psychologie   MeSH
• SARS-CoV-2 MeSH
• uprchlíci * psychologie   MeSH
• úzkost psychologie   epidemiologie   MeSH
• zdravotnický personál * psychologie   statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Ukrajina etnologie   MeSH

Viroids, small circular non-coding RNAs, act as infectious pathogens in higher plants, demonstrating high stability despite consisting solely of naked RNA. Their dependence of replication on host machinery poses the question of whether RNA modifications play a role in viroid biology. Here, we explore RNA modifications in the avocado sunblotch viroid (ASBVd) and the citrus exocortis viroid (CEVd), representative members of viroids replicating in chloroplasts and the nucleus, respectively, using LC - MS and Oxford Nanopore Technology (ONT) direct RNA sequencing. Although no modification was detected in ASBVd, CEVd contained approximately one m6A per RNA molecule. ONT sequencing predicted three m6A positions. Employing orthogonal SELECT method, we confirmed m6A in two positions A353 and A360, which are highly conserved among CEVd variants. These positions are located in the left terminal region of the CEVd rod-like structure where likely RNA Pol II and and TFIIIA-7ZF bind, thus suggesting potential biological role of methylation in viroid replication.

• Klíčová slova
• 6-methyladenosine, LC-MS, m6A SELECT, RNA modification, Viroid, direct RNA-seq,
• MeSH
• konformace nukleové kyseliny MeSH
• kruhová RNA * genetika   metabolismus   MeSH
• nemoci rostlin virologie   MeSH
• posttranskripční úpravy RNA * MeSH
• replikace viru MeSH
• RNA virová * genetika   metabolismus   chemie   MeSH
• sekvenční analýza RNA MeSH
• viroidy * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kruhová RNA * MeSH
• RNA virová * MeSH

Tailocins are nano-scale phage tail-like protein complexes that can mediate antagonistic interactions between closely related bacterial species. While the capacity to produce R-type tailocin was found widely across Gammaproteobacteria, the production of F-type tailocins seems comparatively rare. In this study, we examined the freshwater isolate, Pragia fontium 24613, which can produce both R- and F-type tailocins. We investigated their inhibition spectrum, focusing on clinically relevant enterobacteria, and identified the associated tailocin gene cluster. Transmission electron microscopy confirmed that inactivation of the tape measure protein within the tailocin cluster disrupted R-tailocin production. Comparative analysis of Budviciaceae gene clusters showed high conservation of R-type tailocin genes, whereas F-type tailocin genes were found in only a few species, with little conservation. Our findings indicate a high prevalence of bacteriocin production among underexplored Enterobacteriales species. Detected tailocins showed potential as antimicrobials targeting clinically significant pathogens.

• Klíčová slova
• Antibiotics, Antimicrobial agent, Enterobacteria, Fonticin, Phage tail-like particle, Yersinia enterocolitica,
• MeSH
• antibakteriální látky farmakologie   biosyntéza   MeSH
• bakteriociny * genetika   farmakologie   MeSH
• bakteriofágy * genetika   metabolismus   MeSH
• Enterobacteriaceae * genetika   metabolismus   účinky léků   MeSH
• fylogeneze MeSH
• multigenová rodina MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriociny * MeSH

Lenacapavir (GS-6207) is a capsid inhibitor approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced people with multidrug-resistant HIV-1. Here, this study provides a comprehensive overview of lenacapavir, with a particular focus on its long-acting properties, pharmacodynamics, pharmacokinetics, clinical efficacy and safety, and resistance profile. Clinical trials have demonstrated that long-acting lenacapavir is highly effective not only for treating HIV-1 infection but also as a pre-exposure prophylactic agent. The future development of fixed-dose, long-acting combination regimens incorporating lenacapavir and other long-acting antiretroviral agents offers significant potential for durable and effective HIV-1 management in clinical settings.

• Klíčová slova
• Drug combination, Drug resistance, HIV-1 therapy, Lenacapavir, Pre-exposure prophylaxis,
• MeSH
• HIV infekce * farmakoterapie   prevence a kontrola   metabolismus   MeSH
• HIV-1 * účinky léků   metabolismus   MeSH
• kapsida * účinky léků   metabolismus   MeSH
• látky proti HIV * terapeutické užití   farmakologie   farmakokinetika   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• acetamidy MeSH
• indazoly MeSH
• látky proti HIV * MeSH
• lenacapavir MeSH Prohlížeč

Implementing bacteriophages into dosage forms is a significant step for the practical application of phage therapy. While designing a dosage form, bacteriophages as active ingredients may be exposed to excipients, guaranteeing microbial quality. However, only a few antimicrobial preservatives have been studied regarding their interaction with bacteriophages during long-term storage. Here, the stability of the staphylococcal Kayvirus and pseudomonal Pbunavirus with twelve commonly used preservatives was monitored for thirteen weeks to assess the risk of destabilisation of phage suspensions by excipients. The effectiveness of preservatives on the test bacteria, yeast and mould was determined using a microdilution method and the phage lytic activity by plaque enumeration. The antimicrobial activity of preservatives with bacteriophages was confirmed, except benzalkonium chloride and chlorhexidine digluconate, which showed precipitation and were classified as incompatible. A complete loss of phage potency in both tested phages occurred with diazolidinyl urea and in Kayvirus with benzalkonium chloride. For both phages, a slight decrease in titer, by one order of magnitude, was observed with m-cresol, sodium propionate, sodium benzoate, and phenylethyl alcohol. For Kayvirus, thimerosal, parabens, and mono propylene glycol and for Pbunavirus, phenoxyethanol also met the criteria. The decrease by two or more orders was determined for the remaining cases. This study helps select antimicrobial preservatives for optimizing dosage formulations with the therapeutically applicable bacteriophages.

• Klíčová slova
• Antimicrobial preservative, Bacteriophages, Dosage forms formulations, Excipients, Kayvirus, Pbunavirus, Phage therapy, Pseudomonas aeruginosa, Staphylococcus aureus,
• MeSH
• antiinfekční látky * farmakologie   chemie   MeSH
• bakteriofágy * účinky léků   MeSH
• benzalkoniové sloučeniny farmakologie   chemie   MeSH
• fágová terapie metody   MeSH
• konzervační prostředky farmaceutické * chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• pomocné látky chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiinfekční látky * MeSH
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické * MeSH
• pomocné látky MeSH

BACKGROUND: Clinical disability is among the risk factors of a more severe coronavirus disease of 2019 (COVID-19) course in patients with multiple sclerosis (PwMS), but might provide an insensitive reflection of actual tissue pathology. Brain volume loss has emerged as a magnetic resonance imaging (MRI) proxy of neurodegeneration in PwMS. Our main objective was to investigate whether brain volume predicts COVID-19 severity in PwMS. METHODS: Clinical data of PwMS followed at the Belgian National Multiple Sclerosis (MS) Center in Melsbroek are collected in a local database in case of COVID-19 diagnosis. One hundred ninety-eight unique PwMS with a suitable 3D brain MRI available, conducted maximally 24 months before their COVID-19 infection, were included. RESULTS: An unfavorable outcome due to COVID-19 was noted in fourteen PwMS (hospitalization: 7.1 %, death: 0.5 %). Neither global nor regional normalized brain volumes predicted COVID-19 severity. Similar results were obtained in patients fulfilling the criteria for benign MS. Being unprotected by vaccination was the only variable significantly associated with a poor COVID-19 outcome (OR 3.7; CI 1.2-10.2). We observed a significant worsening of Symbol Digit Modality Test performance in PwMS with the lowest (Q4) whole brain volume, as compared to those with the highest (Q1) (2.2 ± 8.5 versus -1.2 ± 9.1; P = 0.037). CONCLUSION: Brain volume does not predict COVID-19 outcome in PwMS, including those with benign MS. Unvaccinated individuals remain susceptible to developing a more severe infection. PwMS with the most profound pre-existing brain atrophy may be at risk for cognitive deterioration after COVID-19.

• Klíčová slova
• Brain volume loss, COVID-19, Multiple sclerosis, Outcome, SDMT,
• MeSH
• COVID-19 * komplikace   diagnostické zobrazování   MeSH
• dospělí MeSH
• kognitivní dysfunkce * diagnostické zobrazování   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * diagnostické zobrazování   patologie   MeSH
• roztroušená skleróza * diagnostické zobrazování   komplikace   psychologie   patologie   MeSH
• SARS-CoV-2 MeSH
• stupeň závažnosti nemoci MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Belgie MeSH

Cellular RNA-binding proteins (RBPs) are pivotal for the viral lifecycle, mediating key host-virus interactions that promote or repress virus infection. While these interactions have been largely studied in the vertebrate host, no comprehensive analyses of protein-RNA interactions occurring in cells of arbovirus vectors, in particular ticks, have been performed to date. Here we systematically identified the responses of the RNA-binding proteome (RBPome) to infection with a prototype bunyavirus (Uukuniemi virus; UUKV) in tick cells and discovered changes in RNA-binding activity for 283 proteins. In an orthogonal approach, we analysed the composition of the viral ribonucleoprotein by immunoprecipitation of UUKV nucleocapsid protein (N) in infected cells. We found many tick RBPs that are regulated by UUKV infection and associate with viral nucleocapsid protein complexes, and we confirmed experimentally that they impact UUKV infection. This includes the tick homolog of topoisomerase 3B (TOP3B), a protein able to manipulate the topology of RNA, which particularly affected viral particle production. Our data thus reveals the first protein-RNA interaction map for infected tick cells.

• MeSH
• infekce viry z čeledi Bunyaviridae * metabolismus   virologie   MeSH
• interakce hostitele a patogenu MeSH
• klíšťata * virologie   metabolismus   MeSH
• nukleokapsida - proteiny metabolismus   MeSH
• Orthobunyavirus * fyziologie   MeSH
• proteiny vázající RNA * metabolismus   genetika   MeSH
• proteom * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nukleokapsida - proteiny MeSH
• proteiny vázající RNA * MeSH
• proteom * MeSH

BACKGROUND: Early mobilisation (EM) within the first 72 h of ICU admission is essential for preventing ICU-acquired weakness; however, mobilisation rates remained low among mechanically ventilated (MV) COVID-19 patients during the pandemic waves. This study aimed to characterise the association between EM and 60-day outcomes. METHODS: A multicentre observational study conducted by the European Society of Intensive Care Medicine (ESICM) examined mobilisation strategies during the second COVID-19 wave (UNITE-COVIDed2021). All patients with confirmed SARS-COV-2 infection who were in the ICU on the peak day between 1st January and 1st June 2021 were included. The analysis expanded on the UNITE-COVIDed2020 study, comparing the first and second COVID-19 waves using a combined dataset. RESULTS: Data from 2053 patients during the second wave across 103 ICUs in 35 countries were analysed and compared with 4190 patients from the first wave. EM was achieved in 801 (39%) vs. 1114 (27%), p < 0.001, respectively. In the combined cohort, MV on admission significantly reduced the likelihood of EM (OR 0.29, 95% CI: 0.25-0.33, p = 0.001). While EM did not improve ICU or hospital length of stay, it was associated with reduced 60-day mortality (OR 0.74, 95% CI: 0.64-0.86, p = 0.001) and transfer rates to other care facilities (OR 0.74, 95% CI: 0.59-0.94, p = 0.001). CONCLUSION: EM is feasible and beneficial for critically ill COVID-19 patients. It was associated with reduced mortality and lower transfer rates to other care facilities, which underscores the critical role of EM in enhancing patient recovery during a pandemic.

• Klíčová slova
• COVID-19 patients, ESICM, Early mobilisation, ICUAW, Multicentre study, UNITE-COVID,
• MeSH
• časné pohybování * statistika a číselné údaje   metody   MeSH
• COVID-19 * terapie   mortalita   epidemiologie   MeSH
• délka pobytu statistika a číselné údaje   MeSH
• jednotky intenzivní péče MeSH
• kritický stav * MeSH
• lidé středního věku MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• umělé dýchání MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH