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
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- Campylobacter jejuni * genetika MeSH
- genotyp MeSH
- kampylobakterové infekce * mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The case report of a young myope (born in 1997) who was diagnosed with bilateral concentric narrowing of the visual field to 15-20 degrees in 2021 is presented. On eye fundus, the findings were normal with central excavation c/d=0.5 and 0.4, respectively. OCT showed loss of retinal nerve fiber layer - in both vertical quadrants, including a reduction in the ganglion cell complex. Electrophysiological examination (PERG) showed normal retinal responses. Visual evoked responses (PVEP) after stimulation squared a 1 degree decrease in amplitudes, with no prolongation of P100 latency. When stimulated with 15-minute squares, responses were normal (see Supplementary Figure). Magnetic resonance imaging of the brain showed a narrowing of the chiasm. In conclusion, optic chiasm hypoplasia may not always have distinct morphological and functional manifestations. In addition to imaging methods, electrophysiological examination of the visual analyser was of great help for its verification.
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Carotid stenting requires dual antiplatelet therapy to effectively prevent thromboembolic complications. However, resistance to clopidogrel, a key component of this therapy, may lead to persistent risk of these complications. The aim of this study was to determine, if the implementation of routine platelet function testing and adjusting therapy was associated with lower incidence of thromboembolic complications and death. METHODS: All consecutive patients treated with carotid artery stenting in a single institution over 8 years were enlisted in a retrospective study. Platelet function testing was performed, and efficient antiplatelet therapy was set before the procedure. Incidence of procedure-related stroke or death within periprocedural period (0-30 days) was assessed. The results were evaluated in relation to the findings of six prominent randomized control trials. RESULTS: A total of 241 patients were treated for carotid stenosis, seven patients undergo CAS on both sides over time. There was 138 symptomatic (55,6%) and 110 asymptomatic stenoses (44,4%). Five thromboembolic complications (2,01%) occurred, four of them (1,61%) was procedure-related. Two patients died because of procedure-related stroke (0,82%). Incidence of procedure-related stroke or death was significant lower compared to the results of CREST study (2,01% vs. 4,81%, P = 0,0243) in the entire cohorts, and to the results of ICSS study in the symptomatic cohorts (2,86% vs. 7,37%, P = 0,0243), respectively. CONCLUSIONS: Tailored antiplatelet therapy in carotid stenting is safe and seems to be related with lower incidence of procedure-related death or stroke rate. Larger prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard dual antiplatelet should be considered.
- Publikační typ
- časopisecké články MeSH
Fibroblast activation protein (FAP) has been extensively studied as a cancer biomarker for decades. Recently, small-molecule FAP inhibitors have been widely adopted as a targeting moiety of experimental theranostic radiotracers. Here we present a fast qPCR-based analytical method allowing FAP inhibition screening in a high-throughput regime. To identify clinically relevant compounds that might interfere with FAP-targeted approaches, we focused on a library of FDA-approved drugs. Using the DNA-linked Inhibitor Antibody Assay (DIANA), we tested a library of 2667 compounds within just a few hours and identified numerous FDA-approved drugs as novel FAP inhibitors. Among these, prodrugs of cephalosporin antibiotics and reverse transcriptase inhibitors, along with one elastase inhibitor, were the most potent FAP inhibitors in our dataset. In addition, by employing FAP DIANA in the quantification mode, we were able to determine FAP concentrations in human plasma samples. Together, our work expands the repertoire of FAP inhibitors, analyzes the potential interference of co-administered drugs with FAP-targeting strategies, and presents a sensitive and low-consumption ELISA alternative for FAP quantification with a detection limit of 50 pg/ml.
- MeSH
- cefalosporiny chemie farmakologie MeSH
- endopeptidasy * metabolismus MeSH
- knihovny malých molekul farmakologie chemie MeSH
- lidé MeSH
- membránové proteiny * antagonisté a inhibitory metabolismus MeSH
- molekulární struktura MeSH
- rychlé screeningové testy * MeSH
- schvalování léčiv MeSH
- serinové endopeptidasy * metabolismus MeSH
- Úřad Spojených států pro potraviny a léky MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- želatinasy * antagonisté a inhibitory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké MeSH
This article challenges drug prohibition advocated by UN conventions as the prevailing regulatory model for psychoactive substances, highlighting its ineffectiveness, harmfulness and outdated nature. At the same time, the conventions exclude some psychoactive substances from international regulation, leaving control to individual countries. Presenting an innovative approach, this article outlines an approach to the legal regulation of psychomodulatory substances (psychoactive substances with low health and societal risk) in non-medical contexts. Acknowledging the potential benefits of such psychoactive substances and balancing them with potential harms, it suggests stringent rules for marketing, safety, and preventing sales to minors. This approach aims to quell illicit markets, safeguard vulnerable populations, and encourage controlled use. Through a case study of the Czech Republic's introduction of a new category of psychomodulatory substances, this article showcases a paradigm shift from the prevailing repressive approach to drug regulation. This adaptive model effectively navigates the regulatory void, offering a viable alternative to the UN's prohibition framework.
- MeSH
- kontrola léčiv a omamných látek * zákonodárství a právo MeSH
- lidé MeSH
- poruchy spojené s užíváním psychoaktivních látek prevence a kontrola epidemiologie MeSH
- psychotropní léky * zásobování a distribuce MeSH
- zakázané drogy zákonodárství a právo MeSH
- zákonodárství lékové MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Continuous deep septal pacing and signal recording during implantation of left bundle branch pacing (LBBP) lead enables to monitor beat-to-beat changes of electrocardiogram (ECG) and myocardial current of injury (COI) as the lead crosses the septum. OBJECTIVES: This study aimed to characterize patterns of continuous QRS, ST-T, and COI change for monitoring of the lead depth and instantaneous determination of the obtained capture type (LBBP vs left ventricular septal pacing [LVSP]). METHODS: The ECG and COI during lead implantation were scrutinized for sudden changes of V6 R-wave peak time, V1 initial and terminal R-wave amplitude, V3-V6 R-wave amplitude, repolarization pattern and S-wave amplitude in I, V5-V6, and COI drop. The sudden and gradual transition patterns were diagnosed depending on the presence or absence of the above beat-to-beat ECG phenomena, respectively. RESULTS: A total of 212 pacemaker recipients were analyzed; LBBP and LVSP were obtained in 77.4% and 22.6%, respectively. There were 4.7 ± 2.1 and 0.2 ± 0.6 beat-to-beat phenomena in LBBP and LVSP patients, respectively. The sudden transition pattern, recognized in 80.7%, had sensitivity and specificity for LBBP diagnosis of 98.8% and 81.2%, respectively. A sudden drop of COI (29.4 ± 8.5 mV to 12.8 ± 4.9 mV) was observed in 53.9% patients (LBBP was simultaneously obtained in 92.7%). CONCLUSIONS: Capture of left bundle branch during lead penetration is a beat-to-beat phenomenon. Two transseptal transition patterns were identified: 1) sudden, which is typical for obtaining LBBP; and 2) gradual, which is typical for obtaining LVSP. A sudden COI drop, a very observable phenomenon, also identified reaching the left subendocardial area.
- MeSH
- blokáda Tawarova raménka patofyziologie terapie MeSH
- elektrokardiografie * MeSH
- Hisův svazek patofyziologie MeSH
- kardiostimulace umělá metody MeSH
- kardiostimulátor MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční septum patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The transient receptor potential canonical (TRPC) channels are a group of highly homologous nonselective cation channels from the larger TRP channel family. They have the ability to form homo- and heteromers with varying degrees of calcium (Ca2+) permeability and signalling properties. TRPC5 is the one cold-sensitive among them and likewise facilitates the influx of extracellular Ca2+ into cells to modulate neuronal depolarization and integrate various intracellular signalling pathways. Recent research with cryo-electron microscopy revealed its structure, along with clear insight into downstream signalling and protein-protein interaction sites. Investigations using global and conditional deficient mice revealed the involvement of TRPC5 in metabolic diseases, energy balance, thermosensation and conditions such as osteoarthritis, rheumatoid arthritis, and inflammatory pain including opioid-induced hyperalgesia and hyperalgesia following tooth decay and pulpitis. This review provides an update on recent advances in our understanding of the role of TRPC5 with focus on metabolic diseases and pain.
- MeSH
- bolest * farmakoterapie metabolismus MeSH
- kationtové kanály TRPC * metabolismus MeSH
- lidé MeSH
- metabolické nemoci * farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Single-cell RNA sequencing (scRNA-seq) methods are widely used in life sciences, including immunology. Typical scRNA-seq analysis pipelines quantify the abundance of particular transcripts without accounting for alternative splicing. However, a well-established pan-leukocyte surface marker, CD45, encoded by the PTPRC gene, presents alternatively spliced variants that define different immune cell subsets. Information about some of the splicing patterns in particular cells in the scRNA-seq data can be obtained using isotype-specific DNA oligo-tagged anti-CD45 antibodies. However, this requires generation of an additional sequencing DNA library. Here, we present IDEIS, an easy-to-use software for CD45 isoform quantification that uses single-cell transcriptomic data as the input. We showed that IDEIS accurately identifies canonical human CD45 isoforms in datasets generated by 10× Genomics 5' sequencing assays. Moreover, we used IDEIS to determine the specificity of the Ptprc splicing pattern in mouse leukocyte subsets.
- MeSH
- alternativní sestřih MeSH
- analýza jednotlivých buněk metody MeSH
- antigeny CD45 * genetika metabolismus MeSH
- leukocyty metabolismus imunologie MeSH
- lidé MeSH
- myši MeSH
- protein - isoformy genetika MeSH
- sekvenční analýza RNA metody MeSH
- software * MeSH
- stanovení celkové genové exprese metody MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION AND PURPOSE: Mycobacterium (M.) chelonae is responsible for a half of relatively rare nontuberculous mycobacteria (NTM) keratitis. We report a case of M. chelonae keratitis in a woman following sclerocorneal suture extraction after cataract surgery. RESULTS: A 70-year-old woman presented with a red eye and corneal infiltration of her left eye six weeks following sclerocorneal suture extraction after an elective cataract surgery in another institute. She complained of a sharp, cutting pain and photophobia. Since initial corneal scrapes and conjunctival swabs proved no pathogen using culture and PCR methods, non-specific antibiotics and antifungal agents were administered. As keratitis was complicated by an inflammation in the anterior chamber and vitreous, samples of the vitreous fluid were sent for microbiologic examination. DNA of Epstein-Barr virus (EBV) was repeatedly detected. Since the intrastromal abscess had formed, corneal re-scrapings were performed and M. chelonae was detected using culture, MALDI-TOF MS and PCR methods. Therapy was changed to a combination of oral and topical clarithromycin, intravitreal, topical and intracameral amikacin, and oral and topical moxifloxacin. The successful therapy led to stabilization. The optical penetrating keratoplasty was performed and no signs of the infection recurrence were found. CONCLUSIONS: The diagnosis of nontuberculous mycobacterial keratitis is difficult and often delayed. An aggressive and prolonged antimicrobial therapy should include systemic and topical antibiotics. Surgical intervention in the form of corneal transplantation may be required in the active and nonresponsive infection. In the presented case this was necessary for visual rehabilitation due to scarring.
- MeSH
- amikacin terapeutické užití MeSH
- antibakteriální látky * terapeutické užití MeSH
- atypické mykobakteriální infekce * diagnóza farmakoterapie mikrobiologie chirurgie MeSH
- fluorochinolony terapeutické užití MeSH
- keratitida * diagnóza farmakoterapie mikrobiologie chirurgie MeSH
- klarithromycin terapeutické užití MeSH
- lidé MeSH
- moxifloxacin * terapeutické užití MeSH
- Mycobacterium chelonae * izolace a purifikace MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality. DESIGN: Two stage time series analysis. SETTING: 645 locations across 34 countries or regions. POPULATION: Daily mortality data, comprising a total of 109 954 744 all cause, 31 164 161 cardiovascular, and 11 817 278 respiratory deaths from 1980 to 2020. MAIN OUTCOME MEASURE: Association between daily mortality and rainfall events with return periods (the expected average time between occurrences of an extreme event of a certain magnitude) of one year, two years, and five years, with a 14 day lag period. A continuous relative intensity index was used to generate intensity-response curves to estimate mortality risks at a global scale. RESULTS: During the study period, a total of 50 913 rainfall events with a one year return period, 8362 events with a two year return period, and 3301 events with a five year return period were identified. A day of extreme rainfall with a five year return period was significantly associated with increased daily all cause, cardiovascular, and respiratory mortality, with cumulative relative risks across 0-14 lag days of 1.08 (95% confidence interval 1.05 to 1.11), 1.05 (1.02 to 1.08), and 1.29 (1.19 to 1.39), respectively. Rainfall events with a two year return period were associated with respiratory mortality only, whereas no significant associations were found for events with a one year return period. Non-linear analysis revealed protective effects (relative risk <1) with moderate-heavy rainfall events, shifting to adverse effects (relative risk >1) with extreme intensities. Additionally, mortality risks from extreme rainfall events appeared to be modified by climate type, baseline variability in rainfall, and vegetation coverage, whereas the moderating effects of population density and income level were not significant. Locations with lower variability of baseline rainfall or scarce vegetation coverage showed higher risks. CONCLUSION: Daily rainfall intensity is associated with varying health effects, with extreme events linked to an increasing relative risk for all cause, cardiovascular, and respiratory mortality. The observed associations varied with local climate and urban infrastructure.
