The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
- MeSH
- Amphetamine pharmacology MeSH
- Amygdala physiology MeSH
- Hippocampus * physiology MeSH
- Memory Consolidation * physiology MeSH
- Rats MeSH
- Brain physiology MeSH
- Neurons physiology metabolism MeSH
- Nucleus Accumbens * physiology MeSH
- Reward * MeSH
- Memory physiology MeSH
- Cues MeSH
- Prefrontal Cortex physiology MeSH
- Mental Recall * physiology MeSH
- Machine Learning MeSH
- Ventral Tegmental Area * physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
In the study, we employ an affordable, tissue-saving, and precise simultaneous multiplex immunofluorescence method with heat-induced antibody stripping to identify and structurally analyse nigral Lewy bodies in dopaminergic neurones. Analysis of different alpha-synuclein epitopes and proteoforms reveals an almost uniform, onion-like morphology of the Lewy bodies. The N-terminal and C-terminal domains are predominantly accessible to antibody binding in the peripheral shell of the bodies.
- MeSH
- alpha-Synuclein * metabolism analysis MeSH
- Lewy Body Disease pathology MeSH
- Dopaminergic Neurons metabolism pathology MeSH
- Fluorescent Antibody Technique methods MeSH
- Lewy Bodies * metabolism pathology MeSH
- Humans MeSH
- Substantia Nigra * metabolism pathology MeSH
- Hot Temperature MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Úvod: Shigelóza je vysoce nakažlivé průjmové onemocnění s potenciálně velmi závažným průběhem. I s ohledem na třetinový nárůst případů v roce 2023 ve srovnání s rokem předchozím jsme si stanovili za cíl podat přehled aktuálních informací o onemocnění a analyzovat data nahlášených případů shigelózy v České republice (ČR). Metody: Zpracovali jsme narativní rešerši odborné literatury v českém a anglickém jazyce, zejména cílenou na evropské studie od roku 2018. Dále jsme provedli analýzu dat hlášených pod kódem diagnózy A03 v národním systému pro hlášení infekčních nemocí (ISIN) v letech 2018–2023. Soustředili jsme se na hlavní epidemiologické ukazatele, zejména pohlaví, věk, geografickou distribuci, sezonnost a hospitalizace. Použity byly programy Excel (verze 2016), STATA (verze 17) a Datawrapper GmbH. Výsledky: Celkem bylo nahlášeno 681 případů onemocnění shigelózou s průměrnou roční incidencí 1/100 000 obyvatel: do roku 2021 byla incidence mírně vyšší u žen, od roku 2022 evidujeme trend opačný. V pandemických letech byl zaznamenán významný pokles případů. V letech 2022 a 2023 byl počet případů mírně vyšší než v období před pandemií. Nejvíce případů evidujeme v ČR každoročně v měsících srpen až prosinec. Ze všech sérotypů shigel byla nejčastěji detekována S. sonnei (80 %), následovaná S. flexneri (15 %). Incidence na 100 000 obyvatel byla nejvyšší u osob ve věku 5–9 let: 2,6 (chlapci 2,4 a dívky 2,8), dále 1–4 roky: 2,4 (chlapci 2,2, dívky 2,6) a osob ve věku 25–34 let: 1,8 (muži 1,8 a ženy 1,7). Podle krajů byla průměrná roční specifická incidence nejvyšší v krajích Moravskoslezském, Olomouckém a v hlavním městě Praze. Hospitalizováno bylo 27 % případů, nejvíce ve věkových skupinách 25–34 a 5–9 let (shodně 17,9 %). Proporce hospitalizovaných případů v rámci jednotlivých věkových skupin byla nejvyšší ve věkové skupině 75+ let (69 %), dále věkových skupinách 1–4 roky, 5–9 let a 65–74let (32–37 %). V souvislosti s onemocněním bylo vykázáno jedno úmrtí muže ve věku 52 let. V rámci epidemického výskytu bylo nahlášeno 11 % případů. Importováno bylo 39 % nahlášených případů. Závěr: V ČR je shigelóza spíše málo zastoupeným gastrointestinálním onemocněním, přičemž téměř 40 % případů tvoří importované nákazy. V současnosti je hrozbou pro veřejné zdraví především globální šíření multirezistentních kmenů podpořené narůstajícím cestovním ruchem a volnými sexuálními praktikami. Rizikovými skupinami zůstávají děti, imunokompromitované osoby (včetně seniorů) a muži mající sex s muži. Očkování není v Evropě dostupné. Stěžejním je nadále dodržování základních hygienických pravidel, zejména v kolektivech a při práci s potravinami. Důraz by měl být dále kladen na zdravotní edukaci osob, včetně poučení před vycestováním do zahraničí. Důkladná anamnéza, včasné trasování, dohled a racionální volba eventuální antibiotické terapie jsou zásadní. V ČR musí být všechny suspektní kmeny zaslány do NRL ke konfirmaci. Celogenomovou sekvenaci a testy citlivosti na antibiotika je vhodné provádět u všech izolátů.
Introduction: Shigellosis is a highly contagious diarrheal disease, which could potentially be very serious. Considering the onethird increase in cases in 2023 compared to the previous year, we aimed to provide an update on the disease and to analyse data on reported cases of shigellosis in the Czech Republic (CZ). Methods: We conducted a narrative search of the literature in Czech and English, particularly targeting European studies from 2018 onwards. We also analysed data reported under the diagnosis code A03 to the National Infectious Disease Reporting System (ISIN) in 2018–2023. We focused on the main epidemiological indicators, i.e. gender, age, geographical distribution, seasonality, and hospitalizations. Excel (version 2016), STATA (version 17), and Datawrapper GmbH were used. Results: A total of 681 shigellosis cases were reported with an average annual incidence of 1/100,000 population: until 2021, the incidence was slightly higher in women, while from 2022 onwards, the trend was reversed. A significant decrease in cases was recorded in the pandemic years. In 2022 and 2023, the number of cases was slightly higher than in the pre-pandemic period. Most cases were detected in CZ in August and December each year. Of all shigella serotypes, S. sonnei was the most frequently detected (80%), followed by S. flexneri (15%). The incidence per 100.000 population was highest among children aged 5–9 years: 2.6 (boys 2.4 and girls 2.8), followed by 1–4-year-olds: 2.4 (2.2 and 2.6, respectively) and persons aged 25–34 years: 1.8 (males 1.8 and females 1.7). Within individual age group, the average annual specific incidence rates were highest in the Moravian-Silesian and Olomouc regions and the capital city Prague. Hospitalizations accounted for 27% of cases, with the highest numbers in the 25–34 and 5–9 age groups (both 17.9%). The proportion of hospitalized cases was highest in the age groups 75+ (69%), 1–4, 5–9, and 65–74 (32–37%). A 52-year-old man was reported to have die in relation to the disease. Eleven percent of cases were reported in outbreak settings. Thirty-nine percent of reported cases were imported. Conclusions: In CZ, shigellosis is a relatively rare gastrointestinal disease, with nearly 40% of cases being imported. At present, the threat to public health is posed mainly by the global spread of multi-resistant strains linked to increasing tourism and free sexual practices. Children, immunocompromised persons (including the elderly), and men who have sex with men remain risk groups. Vaccination is not available in Europe. Compliance with basic hygiene rules, especially in collectives and when working with food, is still a key concern. Emphasis should also be placed on the health education, including instructions before traveling abroad. A thorough medical history, early tracing, surveillance, and rational choice of antibiotic therapy if appropriate are essential. In CZ, all suspected strains shall be sent to the NRL for confirmation. Whole genome sequencing and antibiotic susceptibility testing should be performed on all isolates.
PURPOSE: This study provides an insight on the extent of muscular variability at the suprascapular notch and elaborates on its anatomical interference in suprascapular nerve arthroscopic decompression procedures. METHODS: The suprascapular notch was dissected and its muscular topography was observed in 115 cadaveric specimens. High resolution imaging of the suprascapular notch was captured by a handheld digital microscope (Q-scope). The supraspinatus and subscapularis muscles were traced as they course at the suprascapular notch vicinity. The omohyoid muscle attachment onto the suprascapular ligament was measured. A scoping review and meta-analysis were done to investigate the observed rare muscular variants. RESULTS: In 3.48%, the suprascapular notch anterior surface was fully covered by the subscapularis muscle. The omohyoid muscle inserted onto the suprascapular ligament in 31.25% and extended up to 3/4th of the suprascapular ligament length in 2.61%. Two rare variant muscles were encountered: subclavius posticus muscle and a newly reported "coracoscapularis muscle". CONCLUSIONS: Four categories of muscles with topographical relationship to the suprascapular notch and its arthroscopic feasibility have been classified: (1) constant muscles not intervening with the suprascapular notch space - supraspinatus muscle; (2) constant muscles with variable positions that can intervene with the suprascapular notch space - subscapularis muscle; (3) constant muscles with variable positions that can intervene with the surgical approach - omohyoid muscle; (4) variable muscles intervening with the suprascapular notch space and surgical approach - subclavius posticus and coracoscapularis muscles. This study elucidates the necessity to assess/secure the omohyoid muscle attachment onto the suprascapular ligament in suprascapular nerve decompression ligamentectomy. LEVEL OF EVIDENCE: V Basic Science Research.
- MeSH
- Anatomic Variation * MeSH
- Arthroscopy * methods MeSH
- Decompression, Surgical methods MeSH
- Muscle, Skeletal * innervation anatomy & histology MeSH
- Middle Aged MeSH
- Humans MeSH
- Scapula innervation anatomy & histology MeSH
- Cadaver * MeSH
- Shoulder Joint innervation surgery anatomy & histology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Feasibility Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Alterations in tricarboxylic acid (TCA) cycle metabolism are associated with hepatic metabolic disorders. Elevated hepatic acetate concentrations, often attributed to high caloric intake, are recognized as a pivotal factor in the etiology of obesity and metabolic syndrome. Therefore, the assessment of acetate breakdown and TCA cycle activity plays a central role in understanding the impact of diet-induced alterations on liver metabolism. Magnetic resonance-based deuterium metabolic imaging (DMI) could help to unravel the underlying mechanisms involved in disease development and progression, however, the application of conventional deuterated glucose does not lead to substantial enrichment in hepatic glutamine and glutamate. This study aimed to demonstrate the feasibility of DMI for tracking deuterated acetate breakdown via the TCA cycle in lean and diet-induced fatty liver (FL) rats using 3D DMI after an intraperitoneal infusion of sodium acetate-d3 at 9.4T. Localized and nonlocalized liver spectra acquired at 10 time points post-injection over a 130-min study revealed similar intrahepatic acetate uptake in both animal groups (AUCFL = 717.9 ± 131.1 mM▯min-1, AUClean = 605.1 ± 119.9 mM▯min-1, p = 0.62). Metabolic breakdown could be observed in both groups with an emerging glutamine/glutamate (Glx) peak as a downstream metabolic product (AUCFL = 113.6 ± 23.8 mM▯min-1, AUClean = 136.7 ± 41.7 mM▯min-1, p = 0.68). This study showed the viability of DMI for tracking substrate flux through the TCA cycle, underscoring its methodological potential for imaging metabolic processes in the body.
- MeSH
- Acetates metabolism MeSH
- Metabolic Flux Analysis MeSH
- Citric Acid Cycle * MeSH
- Deuterium * MeSH
- Liver * metabolism diagnostic imaging MeSH
- Rats MeSH
- Magnetic Resonance Imaging MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Cíl studie: Instilace mitomycinu C (MMC) po transuretrální resekci nádoru močového měchýře (TURBT) snižuje riziko recidivy karcinomu močového měchýře. Cílem práce bylo zhodnocení využívání jednorázové pooperační instilace chemoterapeutika po TURBT na našem pracovišti a důvodů jejího nepodání. Pacienti a metody: Retrospektivní vyhodnocení souboru pacientů po TURBT v letech 2016–2022. Byl hodnocen celkový počet TURBT a celkový počet jednorázových instilací MMC (SS-MMC). Zvláště byla vyhodnocena skupina pacientů, u které nebyl zřejmý důvod k nepodání MMC. Dále byly hodnoceny důvody nepodání MMC. Výsledky: Ve sledovaném období bylo prove - deno 735 TURBT u 538 mužů a 197 žen (průměrný věk 71 let, medián 75 let) a podáno 211 SS-MMC (28,7 %). Po vyřazení pacientů s makroskopicky patrným reziduálním tumorem a paliativní endoresekcí (n = 102) a pacientů s endoresekcí pro jiné důvody než nádor močového měchýře (n = 24) bylo provedeno 609 TURBT, kdy bylo možné aplikovat MMC. V této skupině bylo zastoupení SS-MMC 34,7 %. Nejčastějším identifikovaným důvodem nepodání MMC (n = 398) byla hematurie (n = 83, 20,9 %), perforace stěny močového měchýře (n = 66, 16,6 %) a alergie (n = 4, 1 %). U 245 pacientů (61,6 %) nebylo možné důvod nepodání dohledat. Snížení počtu aplikací v letech 2019 a 2020 bylo dáno výpadkem dostupnosti MMC a epidemií COVID-19. Závěr: Údajů o reálné praxi jednorázové instilace chemoterapeutika po TURBT je málo a svědčí spíše pro její nízké využití. Dle našich dat je podaná přibližně u třetiny potenciálně vhodných pacientů. Interpretaci výsledků ztěžuje nedostatek informací o důvodech nepodání MMC při retrospektivní analýze dokumentace.
Aim of Study: Mitomycin C (MMC) instillation after transurethral resection of bladder tumour (TURBT) reduces the risk of bladder cancer recurrence. The aim of this study was to evaluate the use of single postoperative chemotherapy instillation after TURBT at our institution and the reasons for not administering it. Patients and Methods: A retrospective evaluation of a cohort of patients undergoing TURBT from 2016-2022. The total number of TURBTs and the total number of single-shot MMC instillations (SS-MMC) were evaluated. In particular, the group of patients with no obvious reason for not administering MMC was evaluated. Furthermore, the reasons for not administering MMC were evaluated. Results: During the follow-up period, 735 TURBTs were performed in 538 men and 197 women (mean age 71 years, median 75 years) and 211 SS-MMCs (28.7%) were administered. After excluding patients with macroscopically evident residual tumor and palliative endoresection (n = 102) and patients with endoresection for reasons other than bladder cancer (n = 24), 609 TURBTs were performed when MMCs could be instillated. In this group, the representation of SS-MMC was 34.7%. The most common identified reason for not administering SS-MMC (n = 398) was hematuria (n = 83, 20.9%), bladder wall perforation (n = 66, 16.6%), and allergy (n = 4, 1%). In 245 patients (61.6%), the reason for not administering could not be traced. The reduction in the number of applications in 2019 and 2020 was due to the lack of availability of MMC and the COVID-19 epidemic. Conclusion: Data on the actual practice of single instillation of chemotherapeutic agents after TURBT are scarce and suggest that its use is rather low. According to our data, it is administered in approximately one third of potentially suitable patients. Interpretation of the results is hampered by the lack of information on the reasons for not administering MMC in retrospective analysis of the documentation.
- MeSH
- Cystatin C analysis blood MeSH
- Diabetes Mellitus MeSH
- Diabetic Retinopathy diagnosis MeSH
- Diabetic Nephropathies diagnosis MeSH
- Adult MeSH
- Glomerular Filtration Rate * MeSH
- Cohort Studies MeSH
- Diabetes Complications * diagnosis MeSH
- Creatinine analysis blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Publication type
- Comment MeSH
- Overall MeSH
Although Campylobacter jejuni is the pathogen responsible for the most common foodborne illness, tracing of the infection source remains challenging due to its highly variable genome. Therefore, one of the aim of the study was to compare three genotyping methods (MLST, PFGE, and mP-BIT) to determine the most effective genotyping tool. C. jejuni strains were divided into 4 clusters based on strain similarity in the cgMLST dendrogram. Subsequently, the dendrograms of the 3 tested methods were compared to determine the accuracy of each method compared to the reference cgMLST method. Moreover, a cost-benefit analysis has showed that MLST had the highest inverse discrimination index (97%) and required less workflow, time, fewer consumables, and low bacterial sample quantity. PFGE was shown to be obsolete both because of its low discriminatory power and the complexity of the procedure. Similarly, mP‐BIT showed low separation results, which was compensated by its high availability. Therefore, our data showed that MLST is the optimal tool for genotyping C. jejuni. Another aim was to compare the antimicrobial resistance to ciprofloxacin, erythromycin, and tetracycline in C. jejuni strains isolated from human, water, air, food, and animal samples by two gene sequence-based prediction methods and to compare them with the actual susceptibility of C. jejuni strains using the disc diffusion method. Both tools, ResFinder and RGI, synchronously predict the antimicrobial susceptibility of C. jejuni and either can be used.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Drug Resistance, Bacterial genetics MeSH
- Campylobacter jejuni * genetics MeSH
- Genotype MeSH
- Campylobacter Infections * microbiology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Multilocus Sequence Typing MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.
- MeSH
- Cell Lineage MeSH
- Hyperplasia pathology MeSH
- Myocytes, Cardiac pathology physiology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Animals, Newborn * MeSH
- Cell Proliferation MeSH
- Purkinje Fibers * physiopathology physiology pathology MeSH
- Regeneration * physiology MeSH
- Heart Ventricles * pathology physiopathology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The i-gel® Plus is a modified version of the i-gel® supraglottic airway device. It contains a wider drainage port; a longer tip; ramps inside the breathing channel; and an additional port for oxygen delivery. There has been no prospective evaluation of this device in clinical practice. METHODS: This international, multicentre, prospective cohort study aimed to evaluate the performance of the i-gel Plus in adult patients undergoing elective procedures under general anaesthesia. The primary outcome was overall insertion success rate, defined as the ability to provide effective airway management through the device from insertion until the end of the surgical procedure. Secondary outcomes included device performance and incidence of postoperative adverse events. Data from the first 1000 patients are reported. RESULTS: In total, 1012 patients were enrolled; 12 forms were excluded from the final analysis due to incomplete data leaving 1000 included patients (545 female). Overall insertion success rate was 98.6%, with a first-attempt success rate of insertion of 88.2%. A significant difference between females and males was seen for the overall success rate (97.4% vs. 99.6% respectively) but not for first-attempt successful insertion. Mean (SD) oropharyngeal seal pressure was 32 (7) cmH2O. The only independent factor that increased the risk of first-attempt failure was low operator experience. Complications included desaturation < 85% in 0.6%; traces of blood on the device in 7.4%; laryngospasm in 0.5%; and gastric contents inside the bowl in 0.2% of patients. CONCLUSIONS: The i-gel Plus appears to be an effective supraglottic airway device that is associated with a high insertion success rate and a reasonably low incidence of complications.
- MeSH
- Anesthesia, General MeSH
- Equipment Design MeSH
- Adult MeSH
- Elective Surgical Procedures * MeSH
- Intubation, Intratracheal * instrumentation methods MeSH
- Cohort Studies MeSH
- Laryngeal Masks * MeSH
- Middle Aged MeSH
- Humans MeSH
- Postoperative Complications epidemiology MeSH
- Prospective Studies MeSH
- Aged MeSH
- Airway Management instrumentation methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH