BACKGROUND: Almost all extant organisms use the same, so-called canonical, genetic code with departures from it being very rare. Even more exceptional are the instances when a eukaryote with non-canonical code can be easily cultivated and has its whole genome and transcriptome sequenced. This is the case of Blastocrithidia nonstop, a trypanosomatid flagellate that reassigned all three stop codons to encode amino acids. RESULTS: We in silico predicted the metabolism of B. nonstop and compared it with that of the well-studied human parasites Trypanosoma brucei and Leishmania major. The mapped mitochondrial, glycosomal and cytosolic metabolism contains all typical features of these diverse and important parasites. We also provided experimental validation for some of the predicted observations, concerning, specifically presence of glycosomes, cellular respiration, and assembly of the respiratory complexes. CONCLUSIONS: In an unusual comparison of metabolism between a parasitic protist with a massively altered genetic code and its close relatives that rely on a canonical code we showed that the dramatic differences on the level of nucleic acids do not seem to be reflected in the metabolisms. Moreover, although the genome of B. nonstop is extremely AT-rich, we could not find any alterations of its pyrimidine synthesis pathway when compared to other trypanosomatids. Hence, we conclude that the dramatic alteration of the genetic code of B. nonstop has no significant repercussions on the metabolism of this flagellate.
- MeSH
- Eukaryota genetika MeSH
- genetický kód MeSH
- paraziti * genetika MeSH
- terminační kodon MeSH
- Trypanosoma brucei brucei * genetika MeSH
- Trypanosomatina * genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Changes of white matter integrity in people with multiple sclerosis (MS) were documented following mainly motor/skill acquisitions physical therapy, while following neuroproprioceptive "facilitation, inhibition" (neurofacilitation) only by two pilot studies. Neurofacilitation has potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold. However stronger evidence is missing. AIM: This study investigates whether neurofacilitation (three physical therapy types) induce white matter changes and if they relate to clinical improvement. DESIGN: The Three-Arm Parallel-group Exploratory Trial (NCT04355663). SETTING: Each group underwent different kinds of two months ambulatory therapy (Motor Program Activating Therapy, Vojta's reflex locomotion and Functional Electric Stimulation in Posturally Corrected Position). POPULATION: MS people with moderate disability. METHODS: At baseline and after the program, participants underwent magnetic resonance diffusion tensor imaging (DTI) and clinical assessment. Fractional anisotropy maps obtained from DTI were further analyzed using tract-based spatial statistic exploring the mean values in the whole statistic skeleton. Moreover, additional exploratory analysis in 48 regions of white matter was done. RESULTS: Ninety-two people were recruited. DTI data from 61 people were analyzed. The neurofacilitation (irrespective type of therapy) resulted in significant improvement on the Berg Balance Scale (P=0.0089), mainly driven by the Motor Program Activating Therapy. No statistically significant change in the whole statistic skeleton was observed (only a trend for decrement of fractional anisotropy after Vojta's reflex locomotion). Additional exploratory analysis confirmed significant decrement of fractional anisotropy in the right anterior corona radiata. CONCLUSIONS: Neurofacilitation improved balance without much evidence of white matter integrity changes in people with MS. CLINICAL REHABILITATION IMPACT: The study results point to the importance of neuroproprioceptive "facilitation and inhibition" physical therapy in the management of balance in people with multiple sclerosis; and the potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold.
Explainable artificial intelligence holds a great promise for neuroscience and plays an important role in the hypothesis generation process. We follow-up a recent machine learning-oriented study that constructed a deep convolutional neural network to automatically identify biological sex from EEG recordings in healthy individuals and highlighted the discriminative role of beta-band power. If generalizing, this finding would be relevant not only theoretically by pointing to some specific neurobiological sexual dimorphisms, but potentially also as a relevant confound in quantitative EEG diagnostic practice. To put this finding to test, we assess whether the automatic identification of biological sex generalizes to another dataset, particularly in the presence of a psychiatric disease, by testing the hypothesis of higher beta power in women compared to men on 134 patients suffering from Major Depressive Disorder. Moreover, we construct ROC curves and compare the performance of the classifiers in determining sex both before and after the antidepressant treatment. We replicate the observation of a significant difference in beta-band power between men and women, providing classification accuracy of nearly 77%. The difference was consistent across the majority of electrodes, however multivariate classification models did not generally improve the performance. Similar results were observed also after the antidepressant treatment (classification accuracy above 70%), further supporting the robustness of the initial finding.
- Publikační typ
- časopisecké články MeSH
The adenoma detection rate (ADR) is the primary quality indicator for colonoscopies. The polyp detection rate (PDR) is available from administrative data and does not depend on histology verification. The correlation between PDR and ADR and the ADR/PDR conversion factor in preventive colonoscopies were evaluated. In the prospective study, asymptomatic individuals aged 45-75 years with preventive colonoscopy in 2012-2016 were included. Spearman's correlation coefficient was used to assess PDR/ADR for each endoscopist. Conversion factor predicting ADR from PDR was obtained by linear regression and subsequently compared with adenoma to polyp detection rate quotient. One thousand six hundred fourteen preventive colonoscopies performed by 16 endoscopists in 8 screening colonoscopy centres in the Czech Republic were analysed. Correlation between PDR and ADR in all preventive colonoscopies was high and statistically significant (Rs 0.82; P < 0.001). There was a strong correlation between PDR and ADR in men (Rs 0.74; P = 0.002) and in screening colonoscopies (Rs 0.85; P < 0.001). The conversion factor to convert ADR from PDR was 0.72 in all preventive colonoscopies, 0.76 in FOBT+ colonoscopies and 0.67 in screening colonoscopies. ADR may be replaced by PDR in the assessment of colonoscopy quality. The value of the conversion factor varies according to colonoscopy indication and gender of examined individuals; in this Czech study, it was 0.72 in all preventive colonoscopies. The minimum requested ADR of 25 % corresponds to a PDR of 35 %, when converted with the appropriate conversion factor.
- MeSH
- adenom diagnóza epidemiologie patologie prevence a kontrola MeSH
- administrativní požadavky na zdravotní péči statistika a číselné údaje MeSH
- časná detekce nádoru metody statistika a číselné údaje MeSH
- hodnocení rizik metody statistika a číselné údaje MeSH
- kolon diagnostické zobrazování MeSH
- kolonoskopie statistika a číselné údaje MeSH
- kolorektální nádory diagnóza epidemiologie patologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- plošný screening metody statistika a číselné údaje MeSH
- polypy tlustého střeva diagnóza epidemiologie patologie MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sexuální faktory MeSH
- střevní sliznice diagnostické zobrazování patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
In this work, we studied the biochemical properties and evolutionary histories of catalase (CAT) and ascorbate peroxidase (APX), two central enzymes of reactive oxygen species detoxification, across the highly diverse clade Eugenozoa. This clade encompasses free-living phototrophic and heterotrophic flagellates, as well as obligate parasites of insects, vertebrates, and plants. We present evidence of several independent acquisitions of CAT by horizontal gene transfers and evolutionary novelties associated with the APX presence. We posit that Euglenozoa recruit these detoxifying enzymes for specific molecular tasks, such as photosynthesis in euglenids and membrane-bound peroxidase activity in kinetoplastids and some diplonemids.
- Publikační typ
- časopisecké články MeSH
Kolonická kapslová endoskopie (colon capsule endoscopy, CCE) má potenciál stát se tzv. filtrovým testem u jedinců s pozitivním testem na okultní krvácení do stolice (fecal immunochemical test, FIT). Většina těchto osob nemá na vyšetření optickou kolonoskopií (optical colonoscopy, OC) nález pokročilého adenomu nebo karcinomu, což vyvolává ekonomické otázky a současně zatěžuje pacienty zbytečným invazivním vyšetřením. V České republice probíhá od roku 2016 multicentrická studie zaměřená na využití kapslové kolonoskopie u jedinců s pozitivním FIT. Hlavním cílem studie je určit negativní prediktivní hodnotu druhé generace kolonické kapsle (CCE2) pro polypy ≥ 10 mm. Materiál a metody: Do prospektivní studie byli zařazeni jedinci na třech endoskopických pracovištích v České republice - osoby splňující následující inkluzní kritéria: asymptomatičtí jedinci mezi 50. a 75. rokem, bez rodinné či osobní anamnézy kolorektální neoplazie, s pozitivním imunochemickým testem (cut-off 75 ng/ml). Hlavním sledovaným parametrem je negativní prediktivní hodnota CCE2 pro velké polypy (≥ 10 mm). Dalšími sledovanými parametry byly detekce polypů velikosti ≥ 6 mm, ≥ 10 mm, adenomů ≥ 10 mm a karcinomů, stupeň střevní přípravy (hodnocena jako adekvátní, nebo neadekvátní), tolerance vyšetření nemocnými (na základě dotazníku) a komplikace vyšetření kolonickou kapslí (hodnoceny jako závažné, nebo nezávažné). Výsledky: Dosud bylo ve studii vyšetřeno 248 osob ve všech endoskopických centrech, do dalšího zpracování dat bylo zařazeno 178 osob s kompletním vyšetřením CCE2 a OC. Polypy byly diagnostikovány během OC u 144 jedinců (81 %), polypy ≥ 6 mm a ≥ 10 mm u 90 (51 %), respektive u 47 (26 %) osob. Senzitivita pro polypy ≥ 6 mm a ≥ 10 mm činila 82 % (95% interval spolehlivosti [confidence interval, CI] 73-89 %), respektive 79 % (95% CI 64-89 %). Specificita pro polypy ≥ 6 mm a ≥ 10 mm dosáhla 85 % (95% CI 76-92 %) a 92 % (95% CI 86-96 %). Negativní prediktivní hodnota CCE2 pro polypy ≥ 10 mm dosáhla 92 % (95% CI 86-96 %). Zdravotní sestry identifikovaly 73 polypů ≥ 6 mm z 90 (83 %) a 37 polypů ≥ 10 mm ze 47 (79 %) nalezených na OC. Byla zaznamenána jedna retence kapsle ve stenozujícím tumoru colon ascendens, jiné závažné komplikace nebyly zaznamenány. Kapslovou kolonoskopii jako primární screeningový test preferovalo 66 % vyšetřených. Závěr: CCE2 dosahuje vysoké negativní prediktivní hodnoty pro velké polypy. Jedná se o dobře akceptovanou metodu, která má potenciál stát se filtrovým testem u jedinců s pozitivním FIT.
Background: Fecal immunochemical tests (FIT) have been used as an initial test in CRC screening programs. However, majority of patients don't have advanced neoplasia on colonoscopy. Colon capsule endoscopy (CCE) has the potential to reduce the need for optical colonoscopy (OC). Main aim of the study was negative predictive value (NPV) of the second generation of colon capsule endoscopy (CCE2) for large polyps (≥ 10 mm). The secondary aims were accuracy of detection of all polyps (polyps ≥ 6 mm and ≥ 10 mm) and cancers, number of complications and target population acceptance of both methods (CCE2 and OC). Material and methods: In this multicenter (three gastroenterology units) feasibility study, second generation of colon capsule endoscopy (CCE2) has been prospectively compared with OC in persons with positive semi-quantitative FIT with cut-off level 75 ng/ml. Colonoscopy was performed within 10 hours after capsule ingestion. CCE2 videos were viewed independently by a nurse and a physician, both blinded to the results of OC. Complications were assessed as serious (bleeding, perforation) or mild to moderate. The methods of acceptance were evaluated based on the questionnaire completed after both procedures (CCE2 and OC) were finished. The interim analysis of results is presented. Results: From April 2016, 248 individuals have been enrolled; data from 178 persons has been analyzed. During optical colonoscopy, polyps were diagnosed in 144 persons (81%), polyps ≥ 6 mm and ≥ 10 mm in 90 (51%) and 47 (26%) persons, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm and ≥ 10 mm was 82% (95% confidence interval [CI]: 73-89%) and 79% (95% CI: 64-89%), respectively. The specificity for polyps ≥ 6 mm and ≥ 10 mm reached 85% (95% CI: 76-92%) and 92% (95% CI: 86-96%), respectively. The negative predictive value of CCE2 for polyps ≥ 10 mm was 92% (95% CI: 86-96%). Nurses identified 73 polyps ≥ 6 mm of 90 (83%) and 37 polyps ≥ 10 mm of 47 (79%) found on OC. A total of 119 patients (66%) preferred CCE2 as the primary screening method. Conclusion: Second generation of colon capsule has appeared to have a high negative predictive value for the detection of clinically relevant colorectal neoplasia in screening population. This method might be considered as an adequate tool for colorectal cancer screening.
- Klíčová slova
- kolonická kapslová endoskopie,
- MeSH
- imunochemie metody MeSH
- kapslová endoskopie * metody MeSH
- kolonoskopie metody MeSH
- kolorektální nádory * prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- plošný screening MeSH
- polypy střeva diagnóza MeSH
- polypy tlustého střeva diagnóza MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
Souhrn: Úvod: Kolonická kapslová endoskopie (CCE – colon capsule endoscopy) má potenciál stát se tzv. filtrovým testem u jedinců s pozitivním testem na okultní krvácení do stolice (FIT – faecal immunochemical tests). Hlavním cílem studie je určit negativní prediktivní hodnotu druhé generace kolonické kapsle (CCE2) pro polypy ≥ 10 mm. Materiál a metody: Do prospektivní studie jsou ve třech českých endoskopických pracovištích od roku 2016 zařazováni asymptomatičtí jedinci ve screeningovém věku s pozitivním FIT, bez zvýšeného rizika kolorektální neoplazie, kteří byli vyšetřeni CCE2 (nezávisle popisovanou lékařem a zaškolenou sestrou) a následně bezprostředně i standardní optickou koloskopií (OC – optical colonoscopy). Hlavním sledovaným parametrem byla negativní prediktivní hodnota CCE2 pro velké polypy (≥ 10 mm), dalšími pak detekce polypů velikosti ≥ 6 mm, ≥ 10 mm, adenomů ≥ 10 mm a karcinomů, stupeň střevní přípravy, tolerance vyšetření a komplikace CCE. Výsledky: Dosud bylo do studie zařazeno 248 osob, analyzováno bylo 178 s kompletními výsledky. Polypy byly diagnostikovány OC u 144 jedinců (81 %), polypy ≥ 6 mm a ≥ 10 mm u 90 (51 %), resp. u 47 (26 %) osob. Senzitivita CCE pro polypy ≥ 6 mm a ≥ 10 mm činila 82 % (95% CI 73–89 %), resp. 79 % (95% CI 64–89 %). Specificita pro polypy ≥ 6 mm a ≥ 10 mm dosáhla 85 % (95% CI 76–92 %) a 92 % (95% CI 86–96 %). Negativní prediktivní hodnota CCE2 pro polypy ≥ 10 mm dosáhla 92 % (95% CI 86–96 %). Sestry identifikovaly 73 polypů ≥ 6 mm z 90 (83 %) a 37 polypů ≥ 10 mm ze 47 (79 %) nalezených na OC. Z komplikací CCE byla zaznamenána jedna retence kapsle v nádorové stenóze, jako primární screeningový test preferovalo CCE 66 % vyšetřených. Závěr: CCE2 dosahuje vysokou negativní prediktivní hodnotu pro velké polypy. Jedná se o dobře akceptovanou metodu s potenciálem stát se filtrovým testem u jedinců s pozitivním FIT.
Background: Colon capsule endoscopy (CCE) has the potential to become a so-called filter test in individuals with a positive faecal immunochemical test (FIT). The main objective of the study is to determine the negative predictive value of the second generation colonial capsule (CCE2) for polyps ≥ 10 mm. Material and methods: Since 2016, asymptomatic individuals of screening age with a positive FIT, without an increased risk of colorectal neoplasia, who were examined by CCE2 (independently described by a doctor and a trained nurse) and then immediately by standard optical colonoscopy (OC) have been included in a prospective study in three Czech endoscopic workplaces. The main monitored parameter was the negative predictive value of CCE2 for large polyps (≥ 10 mm), followed by the detection of polyps ≥ 6 mm, ≥ 10 mm, adenomas ≥ 10 mm and carcinomas, intestinal preparation level, examination tolerance, and CCE complications. Results: So far, 248 individuals have been enrolled, and the data from 178 individuals with full results have been analyzed. OC polyps were diagnosed in 144 persons (81%), of whom 90 (51%) and 47 (26%) had polyps ≥ 6 mm and ≥ 10 mm, resp. The sensitivities of CCE2 for polyps ≥ 6 mm and ≥ 10 mm were 82% (95% confidence interval [CI]: 73-89%) and 79% (95% CI: 64-89%), respectively. The specificities for polyps ≥ 6 mm and ≥ 0 mm reached 85% (95% CI: 76-92%) and 92% (95% CI: 86-96%), respectively. The negative predictive value of CCE2 for polyps ≥ 10 mm was 92% (95% CI: 86-96%). Nurses identified 73 polyps ≥ 6 mm in 90 individuals (83%) and 37 polyps ≥ 10 mm in 47 (79%) by OC. A total of 119 patients (66%) preferred CCE2 as the primary screening method. Conclusion: CCE2 achieves a high negative predictive value for large polyps. It is a well-accepted method with the potential of becoming a filter test in individuals with a positive FIT.
- MeSH
- kapslová endoskopie * MeSH
- kolonoskopie * metody MeSH
- kolorektální nádory diagnostické zobrazování prevence a kontrola MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- okultní krev MeSH
- plošný screening MeSH
- polypy střeva diagnostické zobrazování MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
