A benzodiazepine, diazepam, has been the leading antidote for seizures caused by nerve agents, the most toxic chemical weapons of mass destruction, since the 1960s. However, its limitations have often brought questions about its usefulness. Extensive effort has been devoted into exploring alternatives, such as other benzodiazepines, anticholinergics, or glutamate antagonists. However, only few showed clear clinical benefit. The only two options to ultimately reach clinical milestones are Avizafone, a water-soluble prodrug of diazepam adopted by the French and UK armed forces, and intramuscular midazolam, adopted by the US Army. The recently FDA-approved new intramuscular application of midazolam brought several advantages, such as rapid onset of action, short duration with predictable pharmacokinetics, increased water solubility for aqueous injectable solutions, and prolonged storage stability. Herein, we discuss the pitfalls and prospects of using midazolam as a substitute in anticonvulsant therapy with a particular focus on military purposes in combat casualty care. We have also considered and discussed several other alternatives that are currently at the experimental level. Recent studies have shown the superiority of midazolam over other benzodiazepines in the medical management of poisoned casualties. While its use in emergency care is straightforward, the proper dose for soldiers under battlefield conditions is questionable due to its sedative effects.

• MeSH
• antikonvulziva * aplikace a dávkování   terapeutické užití   MeSH
• diazepam * aplikace a dávkování   MeSH
• lidé MeSH
• midazolam * aplikace a dávkování   MeSH
• nervová bojová látka * MeSH
• záchvaty * farmakoterapie   chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Prehabilitation aims to improve patients' physical condition before a stressful event, such as surgery, and enhance recovery. Despite its potential benefits, many emerging prehabilitation programs face challenges in enrolling or retaining patients. In our prehabilitation study PHOCUS, which aims to prepare ovarian cancer patients for surgery, we have also encountered lower acceptance and retention rates. Particularly the most vulnerable patients, who are old and frail, and may benefit the most from the prehabilitation, decline participation due to the complexity of the proposed program. In our review we discussed obstacles and barriers that prevent patients' participation based on both literature and our experience. Among the main reasons are patient's low motivation, high intensity of the program and a lack of social support. To overcome these challenges, we suggest increasing the program's flexibility, adapting the program according to individual patient's needs and enhancing patients' education about the benefits of prehabilitation.

• MeSH
• fyzioterapie v předoperační přípravě * psychologie   MeSH
• lidé MeSH
• motivace MeSH
• nádory vaječníků chirurgie   MeSH
• nádory ženských pohlavních orgánů * rehabilitace   chirurgie   MeSH
• pacientův souhlas se zdravotní péčí psychologie   MeSH
• předoperační péče metody   MeSH
• sociální opora MeSH
• vzdělávání pacientů jako téma metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility.‏ In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, ‏SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated ‏(‏HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.

• MeSH
• body zlomu chromozomu MeSH
• chromozomální aberace MeSH
• cytogenetické vyšetření MeSH
• lidé MeSH
• mužská infertilita * genetika   MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: The aim of this study was to evaluate the association of serum neurofilament heavy chain (sNfH) and chitinase 3-like 1 (sCHI3L1) with treatment response and disease activity in multiple sclerosis (MS). METHODS: This single-center, prospective, observational cohort study was conducted at the MS Centre, University Hospital Ostrava, Czech Republic, from May 2020 to August 2023. sNfH and sCHI3L1 were determined using ELISA. A mixed-effects linear model with a log-transformed outcome variable was applied. RESULTS: We analyzed 459 samples from 57 people with MS. Patients were sampled an average of 8.05 times during 21.9 months of follow-up. Those experiencing a relapse at sampling had a sNfH concentration 50 % higher than those in remission (exp(β) 1.5, 95 % CI 1.15-1.96). A longer duration of treatment was associated with lower sNfH (exp(β) 0.95, 95 % CI 0.94-0.96). Patients switched from low- to high-efficacy disease-modifying therapies (DMTs) had higher sNfH than patients treated with low-efficacy DMTs only (exp(β) 1.95, 95 % CI 1.35-2.81). Higher sCHI3L1 was associated with older age (exp(β) 1.01, 95 % CI 1.00-1.02) and longer DMT use (exp(β) 1.01, 95 % CI 1.00-1.02). sCHI3L1 values were not associated with relapse at the time of sampling, renal function, sex, or type of DMT. CONCLUSION: In contrast to sCHI3L1, sNfH may be a potential biomarker for monitoring treatment response and confirming clinical relapse in MS. Further research is needed to determine the long-term dynamics of sNfH and develop related treatment strategies.

• MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče MeSH
• imunologické faktory aplikace a dávkování   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• neurofilamentové proteiny * krev   MeSH
• prospektivní studie MeSH
• protein CHI3L1 * krev   MeSH
• roztroušená skleróza krev   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• MeSH
• cytodiagnostika * metody   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• molekulární patologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH

Fibrosis contributes to tissue repair, but excessive fibrosis disrupts organ function. Alagille syndrome (ALGS, caused by mutations in JAGGED1) results in liver disease and characteristic fibrosis. Here, we show that Jag1Ndr/Ndr mice, a model for ALGS, recapitulate ALGS-like fibrosis. Single-cell RNA-seq and multi-color flow cytometry of the liver revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration despite cholestasis in Jag1Ndr/Ndr mice. Thymic and splenic regulatory T cells (Tregs) were enriched and Jag1Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive transfer into Rag1-/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1+/+ lymphocytes in response to DSS. Cholestasis induced by BDL in Rag1-/- mice with Jag1Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1-/- mice with Jag1+/+ lymphocytes. Finally, the Jag1Ndr/Ndr hepatocyte expression profile and Treg overrepresentation were corroborated in patients' liver samples. Jag1-dependent hepatic and immune defects thus interact to determine the fibrotic process in ALGS.

• MeSH
• Alagillův syndrom patologie   genetika   MeSH
• buněčná diferenciace * MeSH
• hepatocyty * metabolismus   patologie   MeSH
• jaterní cirhóza * patologie   genetika   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• protein jagged-1 * metabolismus   genetika   MeSH
• regulační T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human cytoplasmic tRNAs contain dihydrouridine modifications at positions 16 and 17 (D16/D17). The enzyme responsible for D16/D17 formation and its cellular roles remain elusive. Here, we identify DUS1L as the human tRNA D16/D17 writer. DUS1L knockout in the glioblastoma cell lines LNZ308 and U87 causes loss of D16/D17. D formation is reconstituted in vitro using recombinant DUS1L in the presence of NADPH or NADH. DUS1L knockout/overexpression in LNZ308 cells shows that DUS1L supports cell growth. Moreover, higher DUS1L expression in glioma patients is associated with poorer prognosis. Upon vector-mediated DUS1L overexpression in LNZ308 cells, 5' and 3' processing of precursor tRNATyr(GUA) is inhibited, resulting in a reduced mature tRNATyr(GUA) level, reduced translation of the tyrosine codons UAC and UAU, and reduced translational readthrough of the near-cognate stop codons UAA and UAG. Moreover, DUS1L overexpression increases the amounts of several D16/D17-containing tRNAs and total cellular translation. Our study identifies a human dihydrouridine writer, providing the foundation to study its roles in health and disease.

• MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• proteosyntéza * MeSH
• RNA transferová * metabolismus   genetika   MeSH
• uridin metabolismus   analogy a deriváty   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Obesity represents a growing problem due to its impacts on human health and reproduction. In this study, we analysed semen quality, sperm DNA integrity and gene-specific CpG methylation in 116 healthy men from normal population. The men were divided into three groups according to their body mass index (BMI), and their ejaculates were analysed using standard methods, sperm chromatin structure assay (SCSA), methylation next generation sequencing (NGS) and amplicon sequencing. The sperm methylation NGS revealed six significantly differentially methylated regions (DMRs). Using subsequent targeted amplicon sequencing in 116 men, two of the DMRs were proved as differentially methylated in sperm of men with normal BMI vs. BMI ≥ 25. The DMRs were located in the EPHA8 and ANKRD11 gene. Also, we detected a significant decline in the EPHA8, ANKRD11 and CFAP46 gene methylation in association with increasing BMI values. The genes EPHA8 and ANKRD11 are involved in the nervous system and brain development; the CFAP46 gene plays a role in a flagellar assembly and is associated with sperm motility. Significantly lower rates of motile and progressive motile sperm were observed in men with BMI ≥ 30. Our results show that excess body weight can modify CpG methylation of specific genes, affect sperm motility, and compromise sperm chromatin integrity. These factors can stand behind the observed reduced fertility in men with obesity. The methylation changes might be transmitted to their offspring through sperm, and become a basis for possible developmental and reproductive issues in the next generation.

• MeSH
• analýza spermatu * MeSH
• chromatin * metabolismus   MeSH
• CpG ostrůvky MeSH
• dospělí MeSH
• index tělesné hmotnosti * MeSH
• lidé MeSH
• metylace DNA * MeSH
• mladý dospělý MeSH
• motilita spermií genetika   MeSH
• obezita genetika   MeSH
• spermie * metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Studijní příručka, která se zaměřuje na první pomoc metodou zážitkové pedagogiky.

• Klíčová slova
• zážitková pedagogika,
• MeSH
• první pomoc MeSH
• urgentní lékařství MeSH
• vyučování MeSH
• zdravotní výchova MeSH
• Publikační typ
• studijní příručka MeSH

• Konspekt
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• zdravotní výchova
• urgentní lékařství

Kniha je určená pre študentov a odborníkov primárne z radov farmaceutov, laborantov. Nevysvetľuje základné mechanizmy a princípy účinku jednotlivých liečiv, ale poskytuje interaktívny pohľad na racionálnu farmakoterapiu v podobe inšpiratívnych informácií, praktických cvičení, modelových situácii a iných zaujímavých úloh.

• MeSH
• farmaceutické služby MeSH
• farmakoterapie MeSH
• gastrointestinální nemoci terapie   MeSH
• infekce dýchací soustavy MeSH
• péče orientovaná na pacienta MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• farmacie a farmakologie
• NLK Publikační typ
• učebnice vysokých škol