PURPOSE: To assess motor performance among Czech paediatric off therapy patients of acute lymphoblastic leukaemia (ALL) and to compare their data with normative data. METHODS: Thirty-nine off therapy patients (21 girls, 18 boys; aged 4-21 years) were evaluated using the Complete Form of the Bruininks-Oseretsky Test Second Edition (BOT-2 CF) approximately 1.5 years post-therapy cessation. Gross and fine motor skills were assessed. Normative data from BOT-2 CF served as the basis for comparison. RESULTS: The total motor composite (p = .381, Cohen's d = 0.14) and overall fine (p = .743; Cohen's d = 0.05) and gross (p=.312; Cohen's d = 0.16) motor performance were similar to the normative data. Motor deficits in manual coordination (p = .018; Cohen's d = 0.45), strength and agility (p = .012; Cohen's d = 0.51), manual dexterity (p < .001; Cohen's d = 0.59) and running speed and agility (p < .001; Cohen's d = 0.97) were identified, along with performance better than the established norms on fine motor integration (p = .048; Cohen's d = 0.33) and bilateral coordination (p = .018; Cohen's d = 0.47). CONCLUSION: The findings suggest nuanced motor skill outcomes in ALL off therapy patients, with both deficits and strengths observed. Comprehensive assessments are vital for tailoring rehabilitation strategies to address the varied impacts of ALL and its treatment on motor skills.

• Klíčová slova
• Bruininks-Oseretsky test of motor proficiency (BOT-2 CF), Paediatric acute lymphoblastic leukaemia (ALL), motor performance deficits, motor skills assessment, rehabilitation in paediatric oncology,
• MeSH
• akutní lymfatická leukemie * patofyziologie   komplikace   farmakoterapie   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• motorické dovednosti * fyziologie   MeSH
• poruchy motorických dovedností * diagnóza   etiologie   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain. INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain.

• Klíčová slova
• Bacteroides, Dopamine, Metabolites, Serotonin, Tryptophan,
• MeSH
• dospělí MeSH
• feces mikrobiologie   chemie   MeSH
• impulzivní chování * fyziologie   MeSH
• kyseliny mastné těkavé metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• násilí * psychologie   MeSH
• neurotransmiterové látky metabolismus   krev   MeSH
• střevní mikroflóra * fyziologie   MeSH
• vězni * psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny mastné těkavé MeSH
• neurotransmiterové látky MeSH

The CE-MS/MS method for the analysis of boswellic acids, natural compounds with anti-inflammatory activity, and nonsteroidal anti-inflammatory drugs (NSAIDs) as potential adulterants of dietary supplements with Boswellia serrata extract is presented for the first time. An aqueous-organic background electrolyte comprising 40 mmol/L ammonium acetate (pH 8.5), methanol, and acetonitrile (5:1:4, v/v/v) was used for the separation of boswellic acids and thirteen NSAIDs in negative electrospray ionization mode. Design-of-experiments-guided optimization of Agilent Jet Stream ion source parameters and adjustments to the sheath liquid composition were conducted to improve sensitivity and prevent capillary breakage inside the nebulizer. The CE-MS/MS method was validated for diclofenac, flurbiprofen, ibuprofen, ketoprofen, phenylbutazone, salicylic acid, and carprofen, meeting the ICH M10 guideline requirements for accuracy, precision, matrix effects, and recovery. The lower limits of quantification ranged from 0.04 to 4 μg/mL for all NSAIDs, providing sufficient sensitivity to detect adulteration. The application of the method to dietary supplements revealed no evidence of NSAID adulteration while highlighting quantitative variations in boswellic acid profiles. Further analysis using CE-HRMS with data-dependent acquisition workflow enabled the identification of additional natural triterpenoids and undeclared compounds, such as citric acid and ascorbic acid.

• Klíčová slova
• Adulteration, Boswellia, Boswellic acids, Capillary electrophoresis, Dietary supplements, Mass spectrometry, NSAID,
• MeSH
• antiflogistika nesteroidní * analýza   MeSH
• Boswellia * chemie   MeSH
• elektroforéza kapilární metody   MeSH
• kontaminace léku * MeSH
• potravní doplňky analýza   MeSH
• rostlinné extrakty * chemie   analýza   MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• triterpeny * analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika nesteroidní * MeSH
• boswellic acid MeSH Prohlížeč
• rostlinné extrakty * MeSH
• triterpeny * MeSH

Compositional data are characterized by the fact that their elemental information is contained in simple pairwise logratios of the parts that constitute the composition. While pairwise logratios are typically easy to interpret, the number of possible pairs to consider quickly becomes too large even for medium-sized compositions, which may hinder interpretability in further multivariate analysis. Sparse methods can therefore be useful for identifying a few important pairwise logratios (and parts contained in them) from the total candidate set. To this end, we propose a procedure based on the construction of all possible pairwise logratios and employ sparse principal component analysis to identify important pairwise logratios. The performance of the procedure is demonstrated with both simulated and real-world data. In our empirical analysis, we propose three visual tools showing (i) the balance between sparsity and explained variability, (ii) the stability of the pairwise logratios, and (iii) the importance of the original compositional parts to aid practitioners in their model interpretation.

• Klíčová slova
• Compositional data, Geochemical data, Pairwise logratios, Sparse PCA,
• Publikační typ
• časopisecké články MeSH

The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, particularly the release of bisphenol A (BPA). BPA is an endocrine-disrupting chemical linked to adverse effects on human health, including reproductive, developmental, and metabolic disorders. Although food contact materials are the primary source of human BPA exposure and the contribution of dental materials is minor, the associated risks cannot be dismissed due to BPA's nonmonotonic dose-response relationship. In 2023, the European Food Safety Authority proposed a 20,000-fold reduction in the tolerable daily intake of BPA to 0.2 ng/kg body weight, citing immune system effects at extremely low doses. This proposal has sparked regulatory and scientific debate, as adopting such a stringent limit would effectively ban the use of BPA in food contact materials and many other products. Given this context, it is essential to assess the release of BPA from dental materials both in vitro and in vivo. However, data interpretation is complicated by methodological inconsistencies, including variations in material composition, specimen preparation, choice of extraction media, experimental duration, and analytical methods. In addition, pivotal differences in reporting results make it difficult to synthesize findings and draw reliable conclusions. This review examines the controversy surrounding BPA, critically evaluates evidence on its release from dental materials, and explores mitigation strategies. By highlighting gaps in knowledge and proposing future research directions, this review aims to provide clinicians, researchers, and policymakers with a clearer understanding of BPA-related complexities, ultimately contributing to patient safety and material innovation.

• Klíčová slova
• biocompatibility, composite materials, endocrinology, resin(s), sealants, toxicology,
• MeSH
• benzhydrylové sloučeniny * škodlivé účinky   analýza   MeSH
• endokrinní disruptory * škodlivé účinky   analýza   MeSH
• fenoly * škodlivé účinky   analýza   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• zubní materiály * chemie   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• fenoly * MeSH
• sloučeniny bisfenolu A MeSH
• zubní materiály * MeSH

AIMS: To evaluate the psychometric properties of the Adelphi Adherence Questionnaire (ADAQ©) as an adherence measure in a diverse type 2 diabetes mellitus (T2DM) population in routine clinical practice. MATERIALS AND METHODS: Data were drawn from the Adelphi T2DM Disease Specific Programme™, a survey of physicians and adults with T2DM consulting in the United States, February-May 2021. Participants completed the ADAQ and single questions on medication satisfaction and convenience. Latent variable modelling (exploratory/confirmatory factor analyses, item response theory, Mokken scaling and bifactor analyses) assessed ADAQ dimensionality and composite scoring. Differential item functioning (DIF) analyses were conducted between participants taking injectable and non-injectable therapies, and with <3 or ≥3 long-term conditions. Correlational analyses with physician-reported adherence and compliance, and patient-reported treatment satisfaction, convenience and side-effects assessed construct validity. ADAQ scores by sociodemographic and clinical factors were also described. RESULTS: Overall, 1287 people with T2DM were included in this analysis (mean age 56.7 years [standard deviation: 12.8], 54.5% [n = 702] male). Latent variable modelling indicated a unidimensional reflective model fit, with a bifactor model confirming an 11-question essentially unidimensional composite score. Negligible DIF was found between groups. Cronbach's alpha and McDonald's omega were both ≥0.90. Moderate correlations with physician-reported adherence and compliance, and patient-reported medication convenience and satisfaction support construct validity. CONCLUSIONS: The ADAQ shows strong construct validity and high internal consistency reliability within a heterogenous T2DM population with negligible DIF between sub-groups. Future work should focus on test-retest reliability and detecting change over time.

• Klíčová slova
• ADAQ, Adelphi adherence questionnaire, MLTC, T2DM, multiple long‐term conditions, psychometric evaluation,
• MeSH
• adherence k farmakoterapii * psychologie   MeSH
• diabetes mellitus 2. typu * farmakoterapie   psychologie   epidemiologie   MeSH
• dospělí MeSH
• hypoglykemika * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• psychometrie MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• spokojenost pacientů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené státy americké epidemiologie   MeSH
• Názvy látek
• hypoglykemika * MeSH

Selection of the optimal makeup solvent composition is critical for achieving sensitive and reproducible ionization in supercritical fluid chromatography-mass spectrometry (SFC-MS). This study investigated the ionization processes in a spray-based ionization source called UniSpray (US), by an artificial neural network driven approach, emphasizing the effect of makeup solvent composition. A set of compounds with different physicochemical properties was analyzed using a generic SFC method and 24 makeup solvents. Artificial neural networks were used to correlate molecular descriptors with MS responses and to identify key analyte properties affecting ionization. Statistical analysis of this extensive dataset revealed significant differences in ionization efficiency compared to electrospray ionization (ESI), depending on makeup solvent composition and analyte properties. While US outperformed ESI for 82 % of compounds, certain analytes, including basic beta-blockers, fluorine-substituted compounds, and small lipophilic molecules, benefited from ESI. Optimized makeup solvent compositions differed notably between ESI and US. For example, ethanol and isopropanol were recommended for US+ but not for ESI+. The use of water and ammonia also affected MS responses differently between sources and ionization modes, with optimal concentrations varying depending on the analyte and organic modifier of the SFC mobile phase. This study highlights key differences between SFC-ESI-MS and SFC-US-MS ionization efficiency and demonstrates the utility of data-driven methodologies for faster and more efficient method development.

• Klíčová slova
• Artificial neural networks, Chemometrics, Electrospray, Mass spectrometry, Supercritical fluid chromatography, UniSpray,
• MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací * metody   MeSH
• hmotnostní spektrometrie * metody   MeSH
• neuronové sítě MeSH
• rozpouštědla chemie   MeSH
• superkritická fluidní chromatografie * metody   MeSH
• umělá inteligence * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• rozpouštědla MeSH

UNLABELLED: Wolbachia pipientis is an obligate intracellular bacterium, associated with several arthropods and filarial nematodes. Wolbachia establishes a variety of symbiotic relationships with its hosts, with consequent genomic rearrangements, variation in gene content, and loss of regulatory regions. Despite this, experimental studies show that Wolbachia gene expression is coordinated with host developmental stages, but the mechanism is still unknown. In this work, we analyzed published RNA-seq data of four Wolbachia strains, finding a correlation between gene nucleotide composition and gene expression. The strength and direction of this phenomenon changed with the expression of the S-adenosyl-methionine-dependent methyltransferase midA. Specifically, when midA is overexpressed, there is a negative relationship between gene adenine content and gene expression, while downregulation of midA reverses this trend. MidA is known to methylate protein arginine, with potential effect on protein affinity for substrates, including nucleic acids. To expand our understanding of this poorly characterized enzyme, we investigated its ability to methylate DNA expressing it in Escherichia coli. The experiment revealed that the Wolbachia MidA can methylate both adenine and cytosine. Lastly, we found upstream the midA gene, a conserved binding site for the Ccka/CtrA signaling transduction system, and we hypothesize that this mechanism could be involved in the communication between the host and the bacterium. Overall, these findings suggest a cascade mechanism in which the host activates the bacterium Ccka/CtrA signaling system, thus inducing the expression of the midA gene, with subsequent effect on the expression of several Wolbachia genes on the basis of their nucleotide composition. IMPORTANCE: Wolbachia pipientis is one of the most common intracellular bacteria in insects, and it is currently utilized as a tool for the control of vector-borne diseases. As for many other endosymbiont bacteria, Wolbachia experienced important genome rearrangements, gene content changes, and the loss of several regulatory sequences, affecting the integrity of operons and promoters. Nevertheless, experimental studies have shown that Wolbachia gene expression is coordinated with the host physiology (e.g., developmental stages), although the underlying mechanism remains unclear. In this work, based on in silico analyses and an experimental study on wOo methyltransferase, we propose that bacterial DNA methylation could be a key mechanism regulating Wolbachia gene expression. Additionally, we found evidence suggesting that the DNA methylation process in Wolbachia can be activated by the host.

• Klíčová slova
• MidA, Wolbachia pipientis, endosymbionts, gene expression, regulation of gene expression,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: With notable improvements in long-term survival and hemocompatibility-related events, heart failure (HF) is emerging as a leading cause of death in the contemporary left ventricular assist device (LVAD) population. While prospective randomized controlled trials (RCTs) have not investigated the use of HF therapies in LVAD recipients, observational data suggest benefits of neurohormonal blockers, especially in achieving blood pressure (BP) targets associated with improved outcomes. METHODS: ENVAD-HF is an investigator-initiated prospective multicenter, randomized, open-label, parallel group, pilot study in HeartMate 3 (HM3) LVAD recipients to evaluate the safety and tolerability and insights on efficacy of sacubitril/valsartan compared to standard of care (SOC) for managing BP. Medically stable LVAD recipients after a recent HM3 implantation or in ambulatory follow-up were eligible for participation and randomized 1:1 to receive sacubitril/valsartan or SOC used for treating BP, both titrated aiming for a mean arterial pressure (MAP) goal 75-90 mmHg over a 12-month follow-up. The primary endpoint, designed to assess the safety and efficacy of sacubitril/valsartan compared to SOC, is a composite of freedom from all-cause death, deterioration in renal function, hyperkalemia or symptomatic hypotension. The occurrence of the primary endpoint will be assessed in the first three months and during the overall duration of the trial (12 months). Other endpoints include clinical and patient-reported outcomes, biomarker and echocardiography assessments during follow-up. RESULTS: ENVAD-HF enrolled 60 patients between February 2021 and March 2024: 17% females, mean age 57±12 years, 67% in ambulatory follow-up, 55% ischemic etiology, 25% receiving an LVAD as destination therapy, with mean baseline MAP 87±7 mmHg and median NTproBNP 2552 (1595-3543] pg/mL. CONCLUSION: ENVAD-HF is the first prospective RCT of pharmacological therapy for management of BP in stable HM3 LVAD recipients achieving target enrolment. It will provide data on safety, tolerability and insights on efficacy of sacubitril/valsartan versus SOC used for treating BP.

• Klíčová slova
• Blood Pressure, Left Ventricular Assist Device, Outcomes, Sacubitril/valsartan,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: It is well established that the cancerous transformation of cells is accompanied by profound alterations in glycosylation. In this study, we demonstrate the diagnostic potential of N-glycan profiling in tissue specimens from patients, primarily representing the two major types of lung cancer: non-small cell and small cell lung cancer. METHODS: Lung tissues and biopsies obtained from surgery and bronchoscopy underwent sample processing and enzymatic digestion. After labeling, glycans were analyzed employing matrix-assisted laser desorption/ionization mass spectrometry. Statistical analysis was conducted using methods following principles of compositional data analysis. RESULTS: Comparison of glycan profiles demonstrated an increase in paucimannose and high mannose glycans in most tumor specimens, including those with inflammation and histological negative for malignancy. Cancerous tissues exhibited more profound changes in glycosylation. Despite the high heterogeneity in profiles, two main groups of not detected glycans in peritumoral tissues, considered as controls, were observed to correlate with cancer progression in patients. One with complex polylactosamine multifucosylated glycans frequently harboring terminal N-acetyl-glucosamine residues. These glycans were present in most tumors, with their numbers and intensities increasing as cancer progressed. In contrast, the second group exhibited polylactosamine glycans sporadically. Instead, the biopsies of several patients with rapid progression displayed a significant presence in a set of tri- and tetra-antennary core fucosylated glycans having mostly unoccupied N-acetyl-glucosamine residues unless carrying additional fucose unit(s). CONCLUSIONS: The results imply distinct glycosylation patterns even in patients with the same histological type of lung cancer, supporting trends toward personalized diagnosis and more tailored therapies. Currently, tissue biopsies remain the gold standard for diagnosing premalignant and malignant lesions in the lung. Expanded knowledge on glycosylation in these lesions could contribute to improved diagnostic accuracy and better monitoring of malignant disease progression in clinical practice.

• Klíčová slova
• N-glycans, Branched glycans, Fucosylation, Glycosylation, Lung cancer, MALDI-MS,
• Publikační typ
• časopisecké články MeSH