Increasingly complex models are being fit to data these days. This is especially the case for Bayesian modelling making use of Markov chain Monte Carlo methods. Tailored model diagnostics are usually lacking behind. This is also the case for Bayesian mediation models. In this paper, we developed a method for the detection of influential observations for a popular mediation model and its extensions in a Bayesian context. Detection of influential observations is based on the case-deletion principle. Importance sampling with weights which take advantage of the dependence structure in hierarchical models is utilized in order to identify the part of the model which is influenced most. We make use of the variance of log importance sampling weights as the measure of influence. It is demonstrated that this approach is useful when interest lies in the impact of individual observations on a subset of model parameters. The method is illustrated on a three-level data set from the field of nursing research, which was previously used to fit a mediation model of patient satisfaction with care. We focused on influential cases on both the second and the third level of the data.

• Klíčová slova
• Bayesian mediation models, importance sampling, influential observations,
• Publikační typ
• časopisecké články MeSH

The paper is motivated by severe concerns regarding currently applied care of the pregnancy-associated breast cancer (PABC) characterised by particularly poor outcomes of the disease. Psychological and ethical aspects play a crucial role in PABC: the highest priority not to damage the foetus significantly complicates any treatment generally, and it is quite usual that patients disclaim undergoing any breast cancer treatment during pregnancy. Although, due to global demographic trends, PABC is far from appearing rarely now, severe societal and economic consequences of the disease are still neglected by currently applied reactive medical approach. These actualities require creating new strategies which should be better adapted to the needs of the society at large by advancing the PABC care based on predictive diagnostic approaches specifically in premenopausal women, innovative screening programmes focused on young female populations, targeted prevention in high-risk groups, and optimised treatment concepts. The article summarises the facts and provides recommendations to advance the field-related research and medical services specifically dedicated to the PABC care.

• Klíčová slova
• Breast cancer, Multi-level diagnostics, Predictive preventive personalised medicine, Pregnancy, Recommendations, Risk assessment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Staphylococcus petrasii is recently described coagulase negative staphylococcal species and an opportunistic human pathogen, still often misidentified in clinical specimens. Four subspecies are distinguished in S. petrasii by polyphasic taxonomical analyses, however a comparative study has still not been done on the majority of isolates and their genome properties have not yet been thoroughly analysed. Here, we describe the phenotypic and genotypic characteristics of 65 isolates and the results of de novo sequencing, whole genome assembly and annotation of draft genomes of five strains. The strains were identified by MALDI-TOF mass spectrometry to the species level and the majority of the strains were identified to the subspecies level by fingerprinting methods, (GTG)5 repetitive PCR and ribotyping. Macrorestriction profiling by pulsed-field gel electrophoresis was confirmed to be a suitable strain typing method. Comparative genomics revealed the presence of new mobile genetic elements carrying antimicrobial resistance factors such as staphylococcal cassette chromosome (SCC) mec, transposones, phage-inducible genomic islands, and plasmids. Their mosaic structure and similarity across coagulase-negative staphylococci and Staphylococcus aureus suggest the possible exchange of these elements. Numerous putative virulence factors such as adhesins, autolysins, exoenzymes, capsule formation genes, immunomodulators, the phage-associated sasX gene, and SCC-associated spermidine N-acetyltransferase gene, pseudouridine and sorbitol utilization operons might explain clinical manifestations of S. petrasii isolates. The increasing recovery of S. petrasii isolates from human clinical material, the multi-drug resistance including methicillin resistance of S. petrasii subsp. jettensis strains, and virulence factors homologous to other pathogenic staphylococci demonstrate the importance of the species in human disease.

• Klíčová slova
• Coagulase-negative staphylococci, MALDI-TOF MS, Methicillin resistance, Mobile genetic elements, Molecular subtyping, Virulence factors,
• MeSH
• faktory virulence genetika   MeSH
• fenotyp MeSH
• genom bakteriální * MeSH
• genomika MeSH
• genotyp MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pulzní gelová elektroforéza MeSH
• ribotypizace MeSH
• rozptýlené repetitivní sekvence * MeSH
• Staphylococcus klasifikace   genetika   patogenita   MeSH
• techniky typizace bakterií MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• faktory virulence MeSH

RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy. METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at - 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management. RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS. CONCLUSIONS AND RECOMMENDATIONS IN THE FRAMEWORK OF 3PM: In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.

• Klíčová slova
• Alcohol toxicity, Cost-efficacy, Dysbiosis, Fecal microbiota transplantation, Gut microbiota, Health policy, Individualized patient profile, Mitochondrial health, Multi-level diagnostics, Patient stratification, Phenotyping, Predictive preventive personalized medicine (PPPM / 3PM), Severe alcohol-associated hepatitis, Survival, Systemic inflammation, Tailored therapy,
• Publikační typ
• časopisecké články MeSH

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

• Klíčová slova
• Adults, Anorexia athletica, Anthropometrics, Artificial intelligence in medicine, BMI deviation, Big data management, Biomarker panel, Body fluids, Body weight, COVID-19, Cancers, Cardiovascular disease, Communicable, Deficits, Disease development, Elderly, Endothelin-1, Fat, Flammer syndrome, Health economy, Health policy, Healthcare, Hypoxic effects, Immune system, Individualised patient profile, Inflammation, Innovative population Screening Programme, Intentional, Manifestation, Medical imaging, Metabolic pathways, Microbiome, Modelling, Molecular patterns, Multi-level diagnostics, Multi-parametric analysis, Neurodegeneration, Neurology, Non-communicable disorders, Nutrition, Overweight, Pathology, Population health, Predictive preventive personalised medicine (3PM/PPPM), Pregnancy, Progression, ROS, Reproductive dysfunction, Sports medicine, Stroke, Systemic ischemia, Underweight, Unintentional, Vasoconstriction, Weight loss, Well-being, Wound healing, Youth,
• Publikační typ
• časopisecké články MeSH

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.

• MeSH
• bilirubin krev   MeSH
• biologické markery krev   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká hyperbilirubinemie krev   diagnóza   terapie   MeSH
• novorozenecká žloutenka krev   diagnóza   terapie   MeSH
• novorozenecký screening * MeSH
• point of care testing * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• bilirubin MeSH
• biologické markery MeSH

A positive correlation of the milk specific conductance (MSC) to the number of cells (r = 0.65) and to the content of chloride ions (r = 0.93) was found on the basis of an examination of 196 udder-quarter milk samples. As indicated by the closeness of the relationship to the number of cells, MSC measurement at a determination level of 41.8% has similar diagnostic effectiveness as the determination of the content of chloride ions (determination level 43.5%) and lactose content (determination level 42.8%), and much higher diagnostic effectiveness than the determination of titration acidity (determination level 23.4%). As indicated by the closeness of the relationship to the content of chloride ions, MSC measurement at a determination level of 86.7% has higher diagnostic effectiveness than the determination of lactose content (determination level 73.9%) and titration acidity (determination level 54.6%). In both comparisons, the highest diagnostic effectiveness was found in assessing the chlorine-sugar number (determination levels of 49.8% and 94.0%). The MSC value, corresponding to the cellulization of 500 . 10(3) cells per ml of milk, was determined from regression: 0.523 S . m-1. The diagnostic congruence of MSC with the number of cells in milk was 81.25%, and with the findings of mastitis test-NK only 54.0%. The variability of the measurements of MSC renders it impossible to use this measurement to indirect multi-step screening of milk cellulization. It is only realistic to distinguish two classes of the measured MSC values: negative and positive.

• MeSH
• chloridy analýza   MeSH
• elektrická vodivost * MeSH
• laktosa analýza   MeSH
• mastitida skotu diagnóza   MeSH
• mléko * analýza   cytologie   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• chloridy MeSH
• laktosa MeSH

Pathological changes in the cortical lamina can cause several mental disorders. Visualization of these changes in vivo would enhance their diagnostics. Recently a framework for visualizing cortical structures by magnetic resonance imaging (MRI) has emerged. This is based on mathematical modeling of multi-component T1 relaxation at the sub-voxel level. This work proposes a new approach for their estimation. The approach is validated using simulated data. Sixteen MRI experiments were carried out on healthy volunteers. A modified echo-planar imaging (EPI) sequence was used to acquire 105 individual volumes. Data simulating the images were created, serving as the ground truth. The model was fitted to the data using a modified Trust Region algorithm. In single voxel experiments, the estimation accuracy of the T1 relaxation times depended on the number of optimization starting points and the level of noise. A single starting point resulted in a mean percentage error (MPE) of 6.1%, while 100 starting points resulted in a perfect fit. The MPE was <5% for the signal-to-noise ratio (SNR) ≥ 38 dB. Concerning multiple voxel experiments, the MPE was <5% for all components. Estimation of T1 relaxation times can be achieved using the modified algorithm with MPE < 5%.

• Klíčová slova
• MR imaging, brain imaging, cortical layers, mathematical modeling, optimization algorithm,
• Publikační typ
• časopisecké články MeSH

A new method of the chlorophyll (Chl) a fluorescence quenching analysis is described, which allows the calculation of values of (at least) three components of the non-photochemical quenching of the variable Chl a fluorescence (q (N)) using a non-linear regression of a multi-exponential function within experimental data. Formulae for coefficients of the "energy"-dependent (DeltapH-dependent) quenching (q (E)), the state-transition quenching (q (T)) and the photo/inhibitory quenching (q (I)) of Chl a fluorescence were found on the basis of three assumptions: (i) the dark relaxation kinetics of q (N), as well as of all its components, is of an exponential nature, (ii) the superposition principle is valid for individual Chl a fluorescence quenching processes and (iii) the same reference fluorescence level (namely the maximum variable Chl a fluorescence yield in the dark-adapted state, F (V)) is used to define both q (N) and its components. All definitions as well as the algorithms for analytical recognition of the q (N) components are theoretically clarified and experimentally tested. The described theory results in a rather simple equation allowing to compute values for all q (N) components (q (E), q (T), q (I)) as well as the half-times of relaxation (tau(1/2)) of corresponding quenching processes. It is demonstrated that under the above assumptions it holds: q (N) = q (E) + q (T) + q (I). The theoretically derived equations are tested, and the results obtained are discussed for non-stressed and stressed photosynthetically active samples. Semi-empirical formulae for a fast estimation of values of the q (N) components from experimental data are also given.

• MeSH
• časové faktory MeSH
• chlorofyl a MeSH
• chlorofyl metabolismus   MeSH
• fazol metabolismus   MeSH
• fluorescence MeSH
• fotochemie metody   MeSH
• kinetika MeSH
• kukuřice setá metabolismus   MeSH
• listy rostlin metabolismus   MeSH
• regresní analýza MeSH
• tma MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorofyl a MeSH
• chlorofyl MeSH

MicroRNAs (miRNAs) are large class of non-coding RNAs that post-transcriptionally regulate gene expression. Their ability of translational repression applied for example on oncogenes or tumor-suppressor genes indicates involvement of miRNAs in multi-step carcinogenesis. Evidences of miRNAs linkage to biological processes like apoptosis, proliferation, differentiation and cell survival are rapidly accumulating. Approximately 50% of miRNAs are located at fragile sites of chromosomes or regions known to be amplified or deleted in human cancer. That is why, non-coding miRNAs seem to be another level of genetic information which regulation is altered or lost during neoplastic growth. Expression profiles of miRNAs are successfully used for molecular classification, more exact diagnosis and prognosis of human cancers and reached analogical analytical characteristics like studies based on DNA micro-arrays technology and profiling of coding transcripts. In this review we attempt to introduce basic knowledge of miRNAs biogenesis and biological functions and in particular summarise reports focused on miRNAs in oncology research area.

• MeSH
• lidé MeSH
• mikro RNA fyziologie   MeSH
• nádory genetika   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH