BackgroundOn 29 January 2024, the European Centre for Disease Prevention and Control distributed an alert about a metronidazole-resistant Clostridioides difficile outbreak of PCR ribotype (RT) 955 in England.AimWe aimed to investigate the presence of RT955 in Czech, Slovak and Polish C. difficile isolates and evaluate different culture media for detecting its metronidazole resistance.MethodsIsolates with binary toxin genes identified as 'unknown' by the WEBRIBO PCR ribotyping database up to 2023 were re-analysed after adding the RT955 profile to the database. The RT955 isolates were characterised by whole genome sequencing and tested for susceptibility to 15 antimicrobials.ResultsWe did not find RT955 in Czech (n = 6,661, 2012-2023) and Slovak (n = 776, 2015-2023) isolates, but identified 13 RT955 cases (n = 303, 2021-2023) in three hospitals in Poland. By whole genome multilocus sequence typing, 10 isolates clustered into one clonal complex including a sequence of United Kingdom strain ERR12670107, and shared similar antimicrobial resistance genes/mutations. All 13 isolates were resistant to ciprofloxacin/moxifloxacin, erythromycin/clindamycin and ceftazidime. All isolates had a mutation in the nimB gene promoter and in NimB (Tyr130Ser and Leu155Ile). The metronidazole resistance was detected in all isolates using brain-heart-infusion agar supplemented with haemin and Chocolate agar. Results were discrepant with the European Committee on Antimicrobial Susceptibility Testing-recommended Fastidious anaerobe agar and Brucella blood agar.ConclusionThe identification of clonally related haem-dependent metronidazole-resistant C. difficile RT955 in multiple hospitals indicates a need for prospective surveillance to estimate its prevalence in Europe.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence * genetika   MeSH
• Clostridioides difficile * genetika   účinky léků   izolace a purifikace   klasifikace   MeSH
• epidemický výskyt choroby MeSH
• klostridiové infekce * epidemiologie   mikrobiologie   farmakoterapie   MeSH
• lidé MeSH
• metronidazol * farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• multilokusová sekvenční typizace MeSH
• polymerázová řetězová reakce MeSH
• ribotypizace * MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Polsko MeSH
• Slovenská republika MeSH

• MeSH
• cytogenetika MeSH
• terminologie jako téma MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• cytologie, klinická cytologie
• genetika, lékařská genetika
• NLK Publikační typ
• kolektivní monografie

OBJECTIVE: Age-at-death estimation is usually done manually by experts. As such, manual estimation is subjective and greatly depends on the past experience and proficiency of the expert. This becomes even more critical if experts need to evaluate individuals with unknown population affinity or with affinity that they are not familiar with. The purpose of this study is to design a novel age-at-death estimation method allowing for automatic evaluation on computers, thus eliminating the human factor. METHODS: We used a traditional machine-learning approach with explicit feature extraction. First, we identified and described the features that are relevant for age-at-death estimation. Then, we created a multi-linear regression model combining these features. Finally, we analysed the model performance in terms of Mean Absolute Error (MAE), Mean Bias Error (MBE), Slope of Residuals (SoR) and Root Mean Squared Error (RMSE). RESULTS: The main result of this study is a population-independent method of estimating an individual's age-at-death using the acetabulum of the pelvis. Apart from data acquisition, the whole procedure of pre-processing, feature extraction and age estimation is fully automated and implemented as a computer program. This program is a part of a freely available web-based software tool called CoxAGE3D, which is available at https://coxage3d.fit.cvut.cz/. Based on our dataset, the MAE of the presented method is about 10.7 years. In addition, five population-specific models for Thai, Lithuanian, Portuguese, Greek and Swiss populations are also given. The MAEs for these populations are 9.6, 9.8, 10.8, 10.5 and 9.2 years, respectively. Our age-at-death estimation method is suitable for individuals with unknown population affinity and provides acceptable accuracy. The age estimation error cannot be completely eliminated, because it is a consequence of the variability of the ageing process of different individuals not only across different populations but also within a certain population.

• MeSH
• acetabulum * diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• software * MeSH
• soudní antropologie * metody   MeSH
• strojové učení * MeSH
• určení kostního věku * metody   MeSH
• zobrazování trojrozměrné * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Epilepsie jsou heterogenní skupinou onemocnění s významným etiologickým podílem patogenních variant v genech exprimovaných v centrálním nervovém systému. Monogenní epilepsie jsou jednotlivě vzácné, prevalence většiny z nich je neznámá, ale pravděpodobně je u většiny menší než 1 : 10 000. Prognózu mají různou v závislosti na postiženém genu a typu patogenní varianty. Ozřejmění genetické příčiny epilepsie může vést nejen ke stanovení rizika opakování epilepsie v rodině, ale v některých případech také k optimalizaci protizáchvatové medikace. V přehledovém článku přinášíme informace o vzácných geneticky podmíněných epilepsiích, u nichž může znalost patogenní varianty přispět k optimalizaci léčby.

Epilepsies are heterogeneous group of diseases with a significant etiological role of pathogenic variants in the genes expressed in the central nervous system. Monogenic epilepsies are individually rare, prevalence of most of them is unknown, but it is probably less than 1 : 10000. The outcome is variable, depending on the affected gene and type of the variant. The identification of the genetic causes of epilepsy can not only determine the risk of recurrence of epilepsy in the family, but in some cases also to optimize anti-seizure medication. In the overview article, we bring information about rare genetically conditioned epilepsies, in which knowledge of the pathogenic variant may contribute to the optimization of treatment.

INTRODUCTION: We report a case series two patients of Guillain-Barré syndrome (GBS) associated with previous COVID-19 that both patients survived. GBS is an immune-mediated disease that affects peripheral nerves and can cause life-threatening complications. CASE REPORTS: In both cases (53-year-old female and 59-year-old male) with severe GBS with complications, the smell of sense was investigated subjectively using Sniffin' sticks identification tests and objectively using objective olfactometry by the evaluation of olfactory event-related potentials (OERPs). Both patients had good results of the subjective Sniffin' sticks identification test without patholgical findings. Results of objective examination of OERPs: the P2-N1 wave complex was equipotent. No olfactory disturbance could be detected in either case, OERPs were plentiful in both cases. CONCLUSION: The presentation of a case series two patients of post-covid GBS are an example of one of the many complications of COVID-19 that can cause prolonged recovery. Despite the severe course of GBS and the long recovery time, both patients returned to normal life. An expanded prospective study is planned for the future to investigate post-covid olfactory impairment. The prevalence of GBS associated with COVID-19 is still unknown but it is evident that both mild and severe forms of GBS have been described in patients.

• MeSH
• Betacoronavirus MeSH
• čich fyziologie   MeSH
• COVID-19 * komplikace   patofyziologie   MeSH
• evokované potenciály * fyziologie   MeSH
• Guillainův-Barrého syndrom * patofyziologie   diagnóza   MeSH
• koronavirové infekce komplikace   patofyziologie   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pandemie MeSH
• poruchy čichu etiologie   patofyziologie   diagnóza   MeSH
• SARS-CoV-2 * MeSH
• virová pneumonie komplikace   patofyziologie   diagnóza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull-down assay followed by non-target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull-down assay combined with NTA proved to be a well-functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments.

• MeSH
• chemické látky znečišťující vodu * analýza   chemie   MeSH
• endokrinní disruptory * chemie   analýza   MeSH
• hmotnostní spektrometrie metody   MeSH
• ligandy MeSH
• odpadní voda chemie   MeSH
• prealbumin * chemie   metabolismus   analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The most significant sexual differences in the human skull are located in the upper third of the face (the frontal bone), which is a useful research object, mainly in combination with virtual anthropology methods. However, the influence of biological relatedness on sexual dimorphism and frontal bone variability remains unknown. This study was directed at sexual difference description and sex classification using the form and shape of the external surface of the frontal bones from a genealogically documented Central European osteological sample (nineteenth to twentieth centuries). The study sample consisted of 47 cranial CT images of the adult members of several branches of one family group over 4 generations. Three-dimensional virtual models of the frontal bones were analyzed using geometric morphometrics and multidimensional statistics. Almost the entire external frontal surface was significantly different between males and females, especially in form. Significant differences were also found between this related sample and an unrelated one. Sex estimation of the biologically related individuals was performed using the classification models developed on a sample of unrelated individuals from the recent Czech population (Čechová et al. in Int J Legal Med 133: 1285 1294, 2019), with a result of 74.46% and 63.83% in form and shape, respectively. Failure of this classifier was caused by the existence of typical traits found in the biologically related sample different from the usual manifestation of sexual dimorphism. This can be explained as due to the increased degree of similarity and the reduction of variability in biologically related individuals. The results show the importance of testing previously published methods on genealogical data.

• MeSH
• čelní kost * diagnostické zobrazování   anatomie a histologie   MeSH
• dospělí MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• pohlavní dimorfismus MeSH
• soudní antropologie * metody   MeSH
• určení pohlaví podle kostry * metody   MeSH
• zobrazování trojrozměrné * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an invasive biopsy. Thus, alternative methods are being sought. Determining oral HPV16 status appears to be a promising alternative. However, it is not used routinely. This prompted us to perform a systematic literature review enabling us to evaluate the diagnostic and predictive ability of this approach. Thirty-four relevant studies were finally selected. For determination of HPV status in OPC, the calculated average sensitivity and specificity for oral sampling was 74% and 91%, respectively, with p16 tumour tissue marker being the gold standard. The method appears to be valuable in monitoring treatment response as well as the biological activity of the tumour, enabling early detection of persistent or relapsing carcinoma sufficiently long before its clinical and/or radiological manifestation. It can also contribute to identification of the primary tumour in cases of metastases of unknown origin. Last but not least, the screening HPV oral testing would help to identify individuals with persistent HPV oral infection who are at increased risk of development of OPC.

• MeSH
• infekce papilomavirem * diagnóza   MeSH
• karcinom * MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádorové biomarkery MeSH
• nádory orofaryngu * diagnóza   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

Sex estimation is one of the crucial trends in cases of findings of unknown skeletal remains in forensics and bioarchaeology. The changing nature of sexual dimorphism (population specificity, secular trend, other external and internal factors influence) brings challenges to developing new methods; and there are new aims to be independent of these changes such, as the method by Musilová et al. (2016). These methods need to be evaluated on different datasets to determine if they are truly reliable among populations from different places and times, in the case of bioarchaeology. This study assessed the application of the aforementioned method on non-European contemporary and ancient populations to identify the reliability of the method on this separate dataset. The study sample consisted of 96 CT scans of skulls from contemporary Egyptians and 54 3D models of skulls from the Egyptian Old Kingdom Period (2700-2180 BC). The classifier method, previously tested on both Czech and French populations, yielded high accuracies (over 90 %) for sex estimation. For the contemporary Egyptian skull sample, the classifier was able to determine males versus females with an 89.59 % accuracy rate and an AUC value (area under the curve - a measure of the combined specificity and sensitivity of the test) of 0.99; this proves that the classifier is reliable even with a lower degree of accuracy. Conversely, the Old Kingdom Period sample yielded a lower level of accuracy at around 70 % (61.11 %, precisely), although with an AUC value of 0.92, the result is not considered reliable.

• MeSH
• hlava MeSH
• lebka diagnostické zobrazování   anatomie a histologie   MeSH
• lidé MeSH
• pohlavní dimorfismus MeSH
• reprodukovatelnost výsledků MeSH
• soudní antropologie * metody   MeSH
• určení pohlaví podle kostry * metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Analýza genomu je efektivním nástrojem pro určení příčin vzácných nemocí a objasnění funkce lidských genů. Genomický přístup by měl být využíván ve všech případech vzácných nemocí s negativními výsledky klinických, biochemických, metabolických, molekulárně biologických a cytogenetických vyšetření. V tomto projektu navrhujeme pokračování a rozšíření našich aktivit ve studiu genetických příčin a molekulárně biologických a buněčně patologických aspektů vzácných nemocí v pediatrické populaci. Pokusíme určit diagnózu a objasnit etiologii onemocnění ve skupině ~ 120 dětí a jejich rodin se vzácným geneticky podmíněným onemocněním neznámé příčiny. K objasnění genetických příčin využijeme kombinace metod sekvenování exomu, genomu a transkriptomu. Následně se zaměříme na charakterizaci patofyziologických aspektů jednotlivých nemocí , pokusíme se nalézt vhodné biomarkery a zavedeme specifické metody pro jejich postnatální, prenatální a prekoncepční diagnostiku. Součástí projektu bude i snaha o definici potenciálních terapeutických cílů případně protokolů pro cílené ovlivnění nemoci.; Genomic analysis is a very efficient diagnostic and gene discovery tool. It should ideally be applied in the diagnosis of all patients with rare diseases when the results of clinical, biochemical, metabolic, molecular and cytogenetic analyses do not lead to a specific diagnosis. In this project we propose continuation and expansion of our long-term efforts in the establishment and characterization of causal genetic and molecular defects, biological principles and pathophysiologic processes in a wide range of rare diseases. We will investigate a group of ~ 120 carefully phenotyped children and their families with rare diseases of pediatric-onset and unknown etiology using a combination of whole exome, whole genome and genome-wide RNA sequencing. Consequently we will focus on clinical, molecular and pathophysiologic characterization of individual genetic defects, identification of disease biomarkers, development of specific methods for postnatal, prenatal and preconception diagnosis and identification of potential therapeutic targets and protocols for specific therapeutic approaches.

• Klíčová slova
• rare diseases, diagnostika, vzácná onemocnění, diagnostics, genomika, genomics, molekulární podstata, molecular basis,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR