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Article: Predictors of Outcome after Direct Aspiration of Basilar Artery Occlusion.

Mako, Miroslav / Krastev, Georgi / Nosáľ, Vladimír / Haring, Jozef / Jakubcová, Denisa / Daniš, Martin / Klepanec, Andrej / Haršány, Ján / Sivák, Štefan / Kurča, Egon

Journal of clinical medicine

2024 Volume 13, Issue 6

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13061576
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Article ; Online: A high‐throughput liquid chromatography‐tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

Žideková, Nela / Pršo, Kristián / Brisudová, Kristína / Babálová, Lucia / Bolek, Tomáš / Sivák, Štefan / Kurča, Egon / Mokry, Juraj / Samoš, Matej / Nosáľ, Vladimír / Kertys, Martin

Journal of Separation Science. 2023 July, v. 46, no. 13 p.e2300084-

2023

Abstract: Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. ... ...

Abstract	Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non‐compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one‐step extraction procedure in 96‐well formate for phospholipid and protein removal was used for sample pre‐treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.
Keywords	chemical species ; detection limit ; drugs ; formates ; guidelines ; humans ; liquid chromatography ; medicine ; patients ; phospholipids ; separation ; spectrometers ; tandem mass spectrometry ; therapeutics
Language	English
Dates of publication	2023-07
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2047990-6
ISSN	1615-9314 ; 1615-9306
ISSN (online)	1615-9314
ISSN	1615-9306
DOI	10.1002/jssc.202300084
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Article ; Online: Induced Pluripotency: A Powerful Tool for In Vitro Modeling.

Zahumenska, Romana / Nosal, Vladimir / Smolar, Marek / Okajcekova, Terezia / Skovierova, Henrieta / Strnadel, Jan / Halasova, Erika

International journal of molecular sciences

2020 Volume 21, Issue 23

Abstract: One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly ... ...

Abstract	One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly acquired the developmental capacity of self-renewal and differentiation into any cells of three germ layers. Before iPSCs can be used routinely in clinical practice, their efficacy and safety need to be rigorously tested; however, iPSCs have already become effective and fully-fledged tools for application under in vitro conditions. They are currently routinely used for disease modeling, preparation of difficult-to-access cell lines, monitoring of cellular mechanisms in micro- or macroscopic scales, drug testing and screening, genetic engineering, and many other applications. This review is a brief summary of the reprogramming process and subsequent differentiation and culture of reprogrammed cells into neural precursor cells (NPCs) in two-dimensional (2D) and three-dimensional (3D) conditions. NPCs can be used as biomedical models for neurodegenerative diseases (NDs), which are currently considered to be one of the major health problems in the human population.
MeSH term(s)	Cell Differentiation/genetics ; Cell Lineage/genetics ; Cell Self Renewal/drug effects ; Cell Self Renewal/genetics ; Cellular Reprogramming/genetics ; Drug Discovery ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/drug effects ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Neurodegenerative Diseases/drug therapy ; Regenerative Medicine
Language	English
Publishing date	2020-11-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21238910
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Article: Oxidative stress parameters and their relation to motor subtype of Parkinson's disease and levodopa treatment status.

Grofik, Milan / Cibulka, Michal / Oleksakova, Jana / Sivak, Stefan / Cierny, Daniel / Tatarkova, Zuzana / Grendar, Marian / Nosal, Vladimir / Ruzinak, Robert / Kurca, Egon / Kolisek, Martin

General physiology and biophysics

2023 Volume 42, Issue 1, Page(s) 77–85

Abstract: Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity ( ... ...

Abstract	Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.
MeSH term(s)	Humans ; Female ; Parkinson Disease/drug therapy ; Levodopa/therapeutic use ; Antioxidants/metabolism ; Oxidative Stress ; Uric Acid ; Glutathione
Chemical Substances	Levodopa (46627O600J) ; Antioxidants ; Uric Acid (268B43MJ25) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2023-01-27
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	791184-1
ISSN	0231-5882
ISSN	0231-5882
DOI	10.4149/gpb_2022051
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Article ; Online: A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma.

Žideková, Nela / Pršo, Kristián / Brisudová, Kristína / Babálová, Lucia / Bolek, Tomáš / Sivák, Štefan / Kurča, Egon / Mokrý, Juraj / Samoš, Matej / Nosáľ, Vladimír / Kertys, Martin

Journal of separation science

2023 Volume 46, Issue 13, Page(s) e2300084

Abstract	Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0-1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.
MeSH term(s)	Humans ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; Anticoagulants ; Dabigatran ; Rivaroxaban ; Chromatography, High Pressure Liquid/methods ; Reproducibility of Results
Chemical Substances	Anticoagulants ; Dabigatran (I0VM4M70GC) ; Rivaroxaban (9NDF7JZ4M3)
Language	English
Publishing date	2023-04-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2047990-6
ISSN	1615-9314 ; 1615-9306
ISSN (online)	1615-9314
ISSN	1615-9306
DOI	10.1002/jssc.202300084
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Article ; Online: Safety and efficacy of simple training protocol in patients after mild traumatic brain injury.

Martinikova, Martina / Ruzinak, Robert / Hnilicova, Petra / Bittsansky, Michal / Grendar, Marian / Babalova, Lucia / Skacik, Pavol / Kantorova, Ema / Nosal, Vladimir / Turcanova Koprusakova, Monika / Sivak, Jozef / Sivakova, Jana / Biringerova, Zuzana / Kolarovszki, Branislav / Zelenak, Kamil / Kurca, Egon / Sivak, Stefan

Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia

2023

Abstract: Aims: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of ... ...

Abstract	Aims: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of selected training protocol in patients after mTBI. Methods: This was a prospective study that included 25 patients with mTBI and 25 matched healthy controls. Assessments were performed in two sessions and included a post-concussion symptoms questionnaire, battery of neurocognitive tests, and magnetic resonance with tractography. Participants were divided into two groups: a passive subgroup with no specific recommendations and an active subgroup with simple physical and cognitive training. Results: The training program with slightly higher initial physical and cognitive loads was well tolerated and was harmless according to the noninferiority test. The tractography showed overall temporal posttraumatic changes in the brain. The predictive model was able to distinguish between patients and controls in the first (AUC=0.807) and second (AUC=0.652) sessions. In general, tractography had an overall predictive dominance of measures. Conclusion: The results from our study objectively point to the safety of our chosen training protocol, simultaneously with the signs of slight benefits in specific cognitive domains. The study also showed the capability of machine learning and predictive models in mTBI patient recognition.
Language	English
Publishing date	2023-05-04
Publishing country	Czech Republic
Document type	Journal Article
ZDB-ID	17196-7
ISSN	1804-7521 ; 1213-8118 ; 0231-5599 ; 0862-481X
ISSN (online)	1804-7521
ISSN	1213-8118 ; 0231-5599 ; 0862-481X
DOI	10.5507/bp.2023.013
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Article ; Online: Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study.

Nosáľ, Vladimír / Petrovičová, Andrea / Škorňová, Ingrid / Bolek, Tomáš / Dluhá, Jana / Stančiaková, Lucia / Sivák, Štefan / Babálová, Lucia / Hajaš, Gabriel / Staško, Ján / Kubisz, Peter / Kurča, Egon / Samoš, Matej / Mokáň, Marián

European journal of clinical pharmacology

2022 Volume 78, Issue 4, Page(s) 557–564

Abstract: Background: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these ... ...

Abstract	Background: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. Patients and methods: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Results: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001). Conclusion: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.
MeSH term(s)	Administration, Oral ; Anticoagulants/adverse effects ; Atrial Fibrillation/complications ; Atrial Fibrillation/drug therapy ; Dabigatran/adverse effects ; Embolic Stroke ; Factor Xa Inhibitors/adverse effects ; Humans ; Prospective Studies ; Pyridones/adverse effects ; Rivaroxaban/adverse effects ; Stroke/drug therapy ; Stroke/prevention & control
Chemical Substances	Anticoagulants ; Factor Xa Inhibitors ; Pyridones ; Rivaroxaban (9NDF7JZ4M3) ; Dabigatran (I0VM4M70GC)
Language	English
Publishing date	2022-01-22
Publishing country	Germany
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-022-03280-8
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Article: Atypický priebeh Wilsonovej choroby: kazuistika a prehľad literatúry.

Nehaj, František / Kubašková, Marianna / Mokáň, Michal / Sokol, Juraj / Nosáľ, Vladimír / Zeleňák, Kamil / Mokáň, Marián

Vnitrni lekarstvi

Winter 2018 Volume 63, Issue 12, Page(s) 980–986

Abstract: Wilson disease (WD) belongs to autosomal recessive genetic metabolic disorders with gene mutation ATP7B located on 13th chromosome. The enzyme ATPase plays an important role in WD. It facilitates excretion of copper into bile. This gene is responsible ... ...

Title translation	Unusual history of Wilson disease: a case report and review of the literature.
Abstract	Wilson disease (WD) belongs to autosomal recessive genetic metabolic disorders with gene mutation ATP7B located on 13th chromosome. The enzyme ATPase plays an important role in WD. It facilitates excretion of copper into bile. This gene is responsible for modification of apoceruloplasmin. In this disease, it leads to insufficient release of copper from organism and accumulation of copper in organs such as liver, brain which can cause dysfunction of a certain organ. According to specific symptoms, we can divide WD into psychiatric, neurologic or hepatic form. The WD usually manifests between 15 and 25 years of age. Hepatic form often occurs sooner, on the contrary, the neurological variant usually occur during the later stages. We present a case report of 45-years-old woman with atypical medical history of WD, in which the diagnostic process was very long and had interdisciplinary character.Key words: brain - copper - diagnostic - genetics - liver - panda - Wilson disease.
MeSH term(s)	Female ; Hepatolenticular Degeneration/diagnosis ; Hepatolenticular Degeneration/physiopathology ; Humans ; Middle Aged
Language	Czech
Publishing date	Winter 2018
Publishing country	Czech Republic
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	138213-5
ISSN	1801-7592 ; 0042-773X
ISSN (online)	1801-7592
ISSN	0042-773X
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Article ; Online: Alzheimer's Disease-Associated SNP rs708727 in

Cibulka, Michal / Brodnanova, Maria / Grendar, Marian / Necpal, Jan / Benetin, Jan / Han, Vladimir / Kurca, Egon / Nosal, Vladimir / Skorvanek, Matej / Vesely, Branislav / Stanclova, Andrea / Lasabova, Zora / Pös, Zuzana / Szemes, Tomas / Stuchlik, Stanislav / Grofik, Milan / Kolisek, Martin

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: ... ...

Abstract	SLC41A1
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Case-Control Studies ; Cation Transport Proteins/genetics ; Epigenesis, Genetic ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Machine Learning ; Male ; Middle Aged ; Parkinson Disease/genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods ; Slovakia
Chemical Substances	Cation Transport Proteins ; SLC41A1 protein, human
Language	English
Publishing date	2022-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031604
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Article: Sensitive SARS-CoV-2 detection, air travel Covid-19 testing, variant determination and fast direct PCR detection, using ddPCR and RT-qPCR methods.

Acta virologica

2023 Volume 67, Issue 1, Page(s) 3–12

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring in air traffic is important in the prevention of the virus spreading from abroad. The gold standard for SARS-CoV-2 detection is RT-qPCR; however, for early and low viral load ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring in air traffic is important in the prevention of the virus spreading from abroad. The gold standard for SARS-CoV-2 detection is RT-qPCR; however, for early and low viral load detection, a much more sensitive method, such as droplet digital PCR (ddPCR), is required. Our first step was to developed both, ddPCR and RT-qPCR methods, for sensitive SARS-CoV-2 detection. Analysis of ten swab/saliva samples of five Covid-19 patients in different stages of disease showed positivity in 6/10 samples with RT-qPCR and 9/10 with ddPCR. We also used our RT-qPCR method for SARS-CoV-2 detection without the need of RNA extraction, obtaining results in 90-120 minutes. We analyzed 116 self-collected saliva samples from passengers and airport staff arriving from abroad. All samples were negative by RT-qPCR, while 1 was positive, using ddPCR. Lastly, we developed ddPCR assays for SARS-CoV-2 variants identification (alpha, beta, gamma, delta/kappa) that are more economically advantageous when compared to NGS. Our findings demonstrated that saliva samples can be stored at ambient temperature, as we did not observe any significant difference between a fresh sample and the same sample after 24 hours (p = 0.23), hence, saliva collection is the optimal route for sampling airplane passengers. Our results also showed that droplet digital PCR is a more suitable method for detecting virus from saliva, compared to RT-qPCR. Keywords: COVID-19; RT-PCR; ddPCR; SARS-CoV-2; nasopharyngeal swab; saliva.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19 Testing ; Air Travel ; Sensitivity and Specificity ; Polymerase Chain Reaction ; RNA, Viral/genetics ; Saliva/chemistry ; Specimen Handling/methods
Chemical Substances	RNA, Viral
Language	English
Publishing date	2023-02-17
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	210452-0
ISSN	1336-2305 ; 0001-723X
ISSN (online)	1336-2305
ISSN	0001-723X
DOI	10.4149/av_2023_101
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