https://hdl.handle.net/20.500.14178/905 2026-08-16T17:33:54Z 2026-08-16T17:33:54Z Houngbedji, Priam-Amedeo Bachtíková, Andrea Boháčová, Jarmila Tabarestani, Parinaz Janďourek, Ondřej Konečná, Klára Ősterreicher, Jan Paterová, Pavla Novák, Martin Bárta, Pavel Záhorszká, Monika Korduláková, Jana Mori, Matteo Meneghetti, Fiorella Zitko, Jan https://hdl.handle.net/20.500.14178/3889 2026-08-05T01:00:16Z 2026-01-01T00:00:00Z

Pyrazinamide-derived 1,2,3-triazoles: Antimicrobial evaluation, selective antimycobacterial activity and mechanism of action insights Houngbedji, Priam-Amedeo; Bachtíková, Andrea; Boháčová, Jarmila; Tabarestani, Parinaz; Janďourek, Ondřej; Konečná, Klára; Ősterreicher, Jan; Paterová, Pavla; Novák, Martin; Bárta, Pavel; Záhorszká, Monika; Korduláková, Jana; Mori, Matteo; Meneghetti, Fiorella; Zitko, Jan A series of pyrazinamide-derived 1,2,3-triazoles featuring systematic chlorination of the pyrazine ring and diverse aryl substituents was synthesized and evaluated for antimycobacterial activity. Biological activity screening revealed broad-spectrum antimycobacterial activity and good selectivity toward mycobacteria over other pathogens, with 11 of the prepared compounds showing activity against Mycobacterium tuberculosis (Mtb) H37Ra and/or Mtb H37Rv (MIC <= 62.5 mu g/mL). Structure-activity relationship analysis showed that 5-Cl substitution on the pyrazine ring was associated with improved antimycobacterial activity, with the best MIC values observed for compound 7 against Mtb H37Ra (MIC =1.98 mu g/mL) and compound 37 against Mtb H37Rv (MIC =1.56 mu g/mL). The tested compounds retained activity against drug-resistant Mtb isolates and partially against naturally resistant Mycobacterium abscessus, while showing low in vitro cytotoxicity in the HepG2 cell line and favorable selectivity indices. During advanced cytotoxicity testing, both compounds 7 and 37 displayed substantially lower hemolytic activity than bedaquiline, indicating a favorable erythrocyte safety profile within the tested concentration ranges. In vivo toxicity testing on Galleria mellonella showed low acute toxicity for both compounds. Mechanistic studies on compounds 7, 27, 31, and 37 revealed reduced biosynthesis of fatty acids and derived lipids, a phenotype consistent with interference with the Fatty Acid Synthase I (FAS I) system.

2026-01-01T00:00:00Z Skálová, Alena Laco, Jan Thompson, Lester D R Bradová, Martina Vander Poorten, Vincent Araújo, Anna Luíza Damaceno Stenman, Göran Leivo, Ilmo Agaimy, Abbas Ferlito, Alfio https://hdl.handle.net/20.500.14178/3807 2026-07-21T01:00:22Z 2026-01-01T00:00:00Z

Recent developments in salivary gland pathology after the WHO 2024 classification: new developments in existing entities and evolving new entities Skálová, Alena; Laco, Jan; Thompson, Lester D R; Bradová, Martina; Vander Poorten, Vincent; Araújo, Anna Luíza Damaceno; Stenman, Göran; Leivo, Ilmo; Agaimy, Abbas; Ferlito, Alfio Parallel to and after publication of the WHO 2024 classification of head and neck tumors, several developments concerning known existing salivary gland tumor entities, but also proposing new evolving tumor entities have been published. This review article describes the most important new developments in salivary gland pathology published through 2022-2025, that were not included in the 5th edition of the WHO Classification of Head and Neck Tumours 2024. This review summarizes these recent developments in both the benign and the malignant tumor categories. Among the recently proposed entities are palisading adenocarcinoma, microcribriform adenocarcinoma, fenestrating adenocarcinoma and skin-analogue poroid carcinoma. Developments in existing carcinoma entities include recognition of mucoacinar carcinoma as subtype of mucoepidermoid carcinoma (MAML2-fused), mucoepidermoid carcinoma without squamous cell differentiation, metatypical adenoid cystic carcinoma, and adenoid cystic carcinoma with prominent tubular hypereosinophilia. In the benign tumor category, recognition of pleomorphic adenoma with canalicular/trabecular phenotype driven by HMGA2 fusions, triphasic basal cell adenoma with S100 protein-positive "stroma", characterized by CTNNB1 mutations, metaplastic Warthin tumor with KRAS mutations and delineation of thymus-like phenotype in non-sebaceous lymphadenoma with recurrent CYLD mutations are the main highlights. Emerging concepts include benign tumor with ductal and papillary morphology (sialadenopapillary ductal tumor). Finally, new grading schemes have been developed/ proposed for acinic cell carcinoma and secretory carcinoma.

2026-01-01T00:00:00Z Chudějová, Kateřina Mattioni Marchetti, Vittoria Zaccaria, Vita Kanova, Stepanka Šrámková, Anna Krůtová, Marcela Ryšková, Lenka Kroneislová, Gabriela Horvathova, Beata Tejkalova, Renata Krejci, Eva Vagnerova, Iva Zemanova, Zuzana Bitar, Ibrahim https://hdl.handle.net/20.500.14178/3743 2026-07-25T01:00:30Z 2026-01-01T00:00:00Z

One-year multicenter surveillance of Fosfomycin resistance Enterobacterales: the rise of FosA3-producing P. mirabilis Chudějová, Kateřina; Mattioni Marchetti, Vittoria; Zaccaria, Vita; Kanova, Stepanka; Šrámková, Anna; Krůtová, Marcela; Ryšková, Lenka; Kroneislová, Gabriela; Horvathova, Beata; Tejkalova, Renata; Krejci, Eva; Vagnerova, Iva; Zemanova, Zuzana; Bitar, Ibrahim The global rise of antimicrobial resistance has renewed interest in fosfomycin (FOS), an old antibiotic with activity against multidrug-resistant Enterobacterales . However, resistance to FOS is increasing, driven by impaired drug uptake, target modification, and by fosA -encoded enzymatic inactivation. This study assessed the prevalence and molecular basis of FOS resistance among Enterobacterales collected in Czech tertiary care hospitals in 2024. A total of 211 preliminary FOS-resistant isolates were obtained from nine hospitals across the Czech Republic, predominantly Proteus mirabilis (n=149) and Escherichia coli (n=57). All isolates showed elevated FOS MICs, and the PPF test identified FosA activity in 34/211 isolates. Carbon-source growth testing demonstrated widespread impairment of GlpT and UhpT transporters (93.8 % affecting both). PCR confirmed fosA genes in 14 isolates (9 P. mirabilis , 5 E. coli ). WGS revealed fosA3 as the dominant variant (85.7 %), followed by fosA4 (14.3 %). P. mirabilis isolates primarily belonged to ST185 and ST135, forming two Czech-specific fosA3 clusters with limited relatedness to international genomes. FosA-producing E. coli displayed broader diversity (ST69, ST58, ST550, ST1308). FosA4 was detected exclusively in E. coli . Most fosA -positive strains co-harbored ESBL genes, predominantly bla <inf>CTX-M-65</inf>. SNP-based phylogenies indicated local clonal circulation of fosA3 -positive P. mirabilis ST185, whereas E. coli isolates showed heterogeneous international linkages. Analysis of GlpT/UhpT/MurA identified numerous amino acid substitutions, though only a minority were predicted to affect protein function. This study documents the first broader emergence of plasmid-mediated FOS resistance in Czech Enterobacterales and underscores the importance of continuous genomic surveillance of fosA -mediated resistance.

2026-01-01T00:00:00Z Surcinelli, Andrea Kalincik, Tomas Roos, Izanne D'amico, Emanuele Lechner-Scott, Jeannette Ozakbas, Serkan Hradilek, Pavel Horáková, Dana Vachová, Marta Panzera, Ivan Ruzza, Stefano Piscaglia, Maria Grazia Gerlach, Oliver Meca-Lallana, Jose Eustasio Valero-Lopez, Gabriel Kermode, Allan G. Fabis-Pedrini, Marzena J. Prevost, Julie Ampapa, Radek Hodgkinson, Suzanne Grand'maison, Francois Khoury, Samia J. John, Nevin A. Peterka, Marek Houskova, Jana Recmanova, Eva Rous, Zuzana Shaygannejad, Vahid Alroughani, Raed Kuhle, Jens Jakob, Gregor Brecl Grammond, Pierre Patti, Francesco Van Der Walt, Anneke Butzkueven, Helmut Foschi, Matteo https://hdl.handle.net/20.500.14178/3728 2026-04-10T01:00:12Z 2026-01-01T00:00:00Z

Comparative effectiveness of anti-CD20 therapies and S1P receptor modulators in late-onset multiple sclerosis: real-world evidence from the MSBase registry Surcinelli, Andrea; Kalincik, Tomas; Roos, Izanne; D'amico, Emanuele; Lechner-Scott, Jeannette; Ozakbas, Serkan; Hradilek, Pavel; Horáková, Dana; Vachová, Marta; Panzera, Ivan; Ruzza, Stefano; Piscaglia, Maria Grazia; Gerlach, Oliver; Meca-Lallana, Jose Eustasio; Valero-Lopez, Gabriel; Kermode, Allan G.; Fabis-Pedrini, Marzena J.; Prevost, Julie; Ampapa, Radek; Hodgkinson, Suzanne; Grand'maison, Francois; Khoury, Samia J.; John, Nevin A.; Peterka, Marek; Houskova, Jana; Recmanova, Eva; Rous, Zuzana; Shaygannejad, Vahid; Alroughani, Raed; Kuhle, Jens; Jakob, Gregor Brecl; Grammond, Pierre; Patti, Francesco; Van Der Walt, Anneke; Butzkueven, Helmut; Foschi, Matteo Background: Late-onset multiple sclerosis (LOMS), defined by symptom onset after age 50, is increasingly recognised as a distinct clinical entity. Evidence comparing disease-modifying therapies (DMTs) in this subgroup remains limited. Objectives: To compare clinical outcomes of anti-CD20 monoclonal antibodies and sphingosine-1-phosphate receptor modulators (S1PRMs) in LOMS. Design: Multicentre, observational cohort study based on real-world data from an international multiple sclerosis registry. Methods: We analysed data from the MSBase registry, including relapsing-remitting LOMS patients treated with anti-CD20 therapies (ocrelizumab, ofatumumab, rituximab) or S1PRMs (fingolimod, ozanimod, siponimod, ponesimod) for >= 6 months. Primary outcomes were annualised relapse rate (ARR), Expanded Disability Status Scale (EDSS) change, confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), and PIRA without MRI activity (PIRMA). Analyses used inverse probability of treatment weighting (IPTW). Causal forest and best linear projector (BLP) models explored effect modification. Results: After weighting, 347 patients (median age 53.7 years; 69% female; median follow-up 6.9 years) were included. No significant differences were found for ARR, EDSS change, CDW, PIRA, or PIRMA. Exploratory analyses suggested greater anti-CD20 benefit in patients with earlier onset (<= 55 years), shorter disease duration (<= 2 years from diagnosis), and lower disability (EDSS < 3). Conclusions: In this real-world LOMS cohort, no statistically significant differences were observed between anti-CD20 and S1PRM therapies. Exploratory analyses suggested anti-CD20 may be associated with better outcomes in selected subgroups; these findings are hypothesis-generating.

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