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150 result(s) for "Stepien, Adam"
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The role of selected NKG2DLs such as MICA, MICB and ULBP4 as potential markers in multiple sclerosis
The interaction between natural killer group 2 members D and their ligands (NKG2D-NKG2DLs) may play a role in the immunopathology of multiple sclerosis (MS). Owing to their measurable presence in biofluids, soluble NKG2DLs may serve as potential biomarkers for disease activity. NKG2DL family proteins have been previously investigated in the central nervous system (CNS) or biofluids of MS patients but have typically been analyzed individually rather than collectively. To our knowledge, this was the first study to comprehensively evaluate soluble forms of MHC class I chain-related proteins A and B (MICA and MICB), UL16 binding protein 4 (ULBP4), and neurofilament light chains (NFLs) in the serum and cerebrospinal fluid (CSF) of relapsing-remitting MS patients, patients with multifocal demyelinating CNS damage (Pre-MS observation group), and a control group. Results revealed comparable levels of NKG2DLs in the serum and CSF between the groups. This suggested that they may not be suitable as diagnostic and predictive markers in MS. However, the analysis confirmed the established significance of NFL, demonstrating its elevated levels in CSF and serum from MS patients compared with other groups, along with a notable correlation between NFL levels in serum and CSF.
Amygdala volume changes as a potential marker of multiple sclerosis progression: links to EDSS scores and PIRA
Brain atrophy may be a promising marker of relapsing-remitting multiple sclerosis (RRMS) progression, yet it remains underutilized in clinical practice. This exploratory study evaluated correlations between disability-as measured by the Expanded Disability Status Scale (EDSS) and progression independent of relapse activity (PIRA)-and volumetric changes in RRMS patients treated with cladribine tablets (CLAD) or alemtuzumab (ALEM). Clinical and magnetic resonance imaging (MRI) data from patients with RRMS were retrospectively analyzed at four time points: pretreatment and annually over three years of follow-up. Volumetric measurements were obtained using FreeSurfer. Annual volumetric and EDSS changes were pooled together to assess short-term associations and patient-wise longitudinal analyses were performed. 33 patients treated with CLAD and 19 patients treated with ALEM were included. Analyzing year-to-year correlations, a significant positive correlation was found between EDSS and amygdala volume changes (p = 0.00009, η²=0,15657). It was also observed for the pallidum (p=0,02605, η²=0,05384). On the contrary, a negative correlation between thalamic volume changes and EDSS in CLAD group was noted (p=0,04551, η²=0,07203).When comparing annual percentage volume changes across three groups-years with EDSS progression (n = 10), regression (n = 11), and no changes (n = 74)-significant differences were reported in amygdala (p=0,00640; 1.98%, -4%, -0.8%), thalamus (p = 0,04390; -0.54%, 2.98%, 0.1%) and pallidum (p = 0,02904; 1.98%, -6.96%, -0.23%). Finally, among the 10 patients with EDSS progression, an increase in amygdala volume was observed in 3 patients with PIRA, whereas it was not seen in the 7 patients whose EDSS progression was associated with relapsing activity (p = 0.0188; 4.60% vs. 0.004%). Over three years of follow-up in RRMS patients, EDSS progression was positively associated with increases in amygdala-and, to a lesser extent, pallidum-volumes, while worsening disability correlated with thalamic atrophy. Notably, amygdala enlargement was exclusive to patients with PIRA versus relapse-associated worsening, highlighting its potential as a volumetric biomarker of disease progression. However it was exploratory, hypothesis-generating observation and further studies are warranted to validate these findings and elucidate the underlying mechanisms.
Application of Liquid Chromatography Coupled to Mass Spectrometry in Quality Assessment of Dietary Supplements—A Case Study of Tryptophan Supplements: Release Assay, Targeted and Untargeted Studies
Dietary supplements are widely consumed in the EU and the USA. Based on their similarity to pharmaceuticals, consumers mistakenly believe that dietary supplements have also been approved for safety and efficacy. However, in the absence of mandatory testing, data on supplement quality is scarce. Thus, we applied liquid chromatography coupled with tandem mass spectrometry to analyse the quality of dietary supplements containing tryptophan (Trp). We examined 22 supplements in tablets or capsules, produced in the USA, Great Britain, Germany, France, Czech Republic, and Poland. Trp release, crucial for bioavailability and efficiency, was assessed. Additionally, we performed a qualitative analysis of the main ingredient and screened for contaminants. Among the contaminants, we detected Trp’s metabolites, condensation products of Trp and carbonyl compounds, Trp degradation products, degradation products of kynurenine, and other contaminants such as glucosamine and melatonin. The main ingredient content was in the range of 55–100% in capsules and 69–87% in tablets. Surprisingly, almost no Trp release was noted from some supplements. Our study confirms the need to advance research on supplements. We believe that the high-quality analysis of supplements based on reliable analytical techniques will be an important contribution to the discussion on the regulatory framework of these products.
Assessment of brain atrophy as a promising marker of radiological activity in patients with relapsing–remitting multiple sclerosis
The measurement of brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS) may be a marker of the disease activity. However, currently this method is not widely used in clinical practice. In the presented study, the relationship between lesions (T2) in magnetic resonance imaging (MRI), including contrast-enhancing (Gd+), clinical relapses and no evidence of disease activity (NEDA-3) with volumetric changes was investigated. Clinical and MRI data from RRMS patients treated with cladribine tablets (CLAD) and alemtuzumab (ALEM) were retrospectively analyzed at 4 time points (pretreatment and 3 years of follow-up). Volumetric data were obtained using the FreeSurfer. Annual volumetric changes and new T2/Gd + lesions were pooled together to assess short-term relationships, baseline T2/Gd + lesions were correlated with 3-year volume changes and years with NEDA-3 and without NEDA-3 were compared. The study included 33 patients treated with CLAD and 19 patients treated with ALEM. In the year-to-year analysis (n = 59, n = 36) within the CLAD group, new T2 lesions were significantly associated with a decrease in thalamic ( = 0.02), cerebellum ( = 0.05) and deep grey matter ( = 0.05) volume. When analyzing the correlation between baseline T2 lesions and overall 3-year volume changes (N = 9, N = 7), in the CLAD group, strong associations were found with whole brain (  = 0.001, = -0.89), cerebellum (  = 0.002, = -0.20), cerebellar cortex (  = 0.003, = -0.19) and DGM ( = 0.015, = -0.04) atrophy, as well as with lateral ventricular volume increase (  = 0.00001, = 0.1). A similar situation occurred when only the first year of treatment was analyzed (N = 29, N = 13). It was not observed in the ALEM group. Interestingly, no correlation was noted between Gd + lesions and volumetric changes. Remarkably, no statistically significant differences between years with and without relapses were observed. However, years without NEDA-3 (  = 31) were characterized by greater atrophy in white matter (  = 0.04), thalamus (  = 0.02), and putamen (  = 0.04). The results of the presented study suggested an association of increased brain atrophy with radiological activity rather than with relapsing disease activity. However, further studies with larger numbers of patients are needed to verify these associations more precisely.
The Influence of Therapy Enriched with the Erigo®Pro Table and Motor Imagery on the Body Balance of Patients After Stroke—A Randomized Observational Study
Purpose: Impaired balance leads to loss of function, e.g., the inability to walk safely. Therefore, restoring balance is a common goal of rehabilitation after a stroke. An innovative motor imaging and robotic device, the Erigo®Pro walking table, was used to improve balance in patients who had suffered an acute stroke. Materials and Methods: Sixty-six stroke patients in the acute phase with an average age of 64.85 ± 18.62 years were randomly assigned to one of three groups (22 subjects each) and treated with different therapies (conventional, conventional with Erigo®Pro, and conventional with Erigo®Pro enriched with motor imaging). The duration of therapy was two weeks. Patients were assessed before and after completion of therapy. The study used the trunk stability test and the Berg Balance Scale to assess balance, and the Riablo™ device to measure static balance. In addition, an assessment of the superficial tension of the transversus abdominis and multifidus muscles was performed. The clinical trial registration URL unique identifier was NCT06276075. Results: In each of the groups studied, the therapies applied resulted in significant improvement in functional assessment of trunk stability and balance (TCT < 0.001 and BBS < 0.001). The assessment of balance in the frontal (p = 0.023) and sagittal (p = 0.074) planes with the Riablo™ device confirmed the superiority of motor imaging-enhanced therapy at the level of a statistical trend. The tension of the transversus abdominis was higher at the second measurement (M = 14.41; SE = 3.31). Conclusions: Motor imagery-enhanced therapy is most important, both for trunk stability and functional improvement of body balance parameters and for increasing transversus abdominis muscle tension.
Assessment of the impact of reconstitution therapies—cladribine tablets and alemtuzumab—on the atrophy progression among patients with relapse-remitting multiple sclerosis
Immune reconstitution therapies (IRT) are highly effective therapies for multiple sclerosis (MS). Among IRT, we can distinguish partially selective therapies such as cladribine in tablets (CLAD) and non-selective therapies, which include alemtuzumab (ALEM). Today, it is known that these therapies are effective in controlling the relapse activity of the disease and the progression of clinical disability, which has been proven both in clinical trials and in real world evidence (RWE). However, there is a lack of data assessing the effect of IRT on the neurodegenerative process, which is intensified in patients with MS. The aim of the study was to assess the effect of IRT treatment on the degree and pattern of brain atrophy in patients with MS during 3 years of observation. Patients with relapsing-remitting MS (RRMS) treated with CLAD and ALEM were retrospectively recruited for the study. Demographic, clinical, and magnetic resonance imaging (MRI) data were collected at 4 time points: before the treatment and one, two, and three years after the treatment. MRI examinations were analyzed volumetrically using Freesurfer software. Global and regional changes in atrophy were assessed by calculating percentage changes in volume between time points. Results of drug groups were compared with each other. After 3 years of follow-up, statistically significant differences between groups were observed in hippocampus [ < 0.01] and amygdala volume changes [ < 0.01]. Ventral diencephalon atrophy was noted in both groups. On the other hand, in both groups, no significant atrophy of white and grey matter was noted. In addition, an increase in the thalamus volume was observed. In the studied groups, IRT therapies were shown to slow down the atrophy process in MS patients to a similar extent. These therapies may play a neuroprotective role by increasing the volume of the thalamus and hippocampus. The study was limited by the small number of both groups. Therefore, further studies are needed to fully assess the effect of reconstitution therapies on neurodegenerative processes in patients with RRMS.
Selected Materials and Technologies for Electrical Energy Sector
Ensuring the energy transition in order to decrease CO2 and volatile organic compounds emissions and improve the efficiency of energy processes requires the development of advanced materials and technologies for the electrical energy sector. The article reviews superconducting materials, functional nanomaterials used in the power industry mainly due to their magnetic, electrical, optical, and dielectric properties and the thin layers of amorphous carbon nitride, which properties make them an important material from the point of view of environmental protection, optoelectronic, photovoltaic and energy storage. The superconductivity-based technologies, material processing, and thermal and nonthermal plasma generation have been reviewed as technologies that can be a solution to chosen problems in the electrical energy sector and environment. The study explains directly both—the basics and application potential of low and high-temperature superconductors as well as peculiarities of the related manufacturing technologies for Roebel cables, 1G and 2G HTS tapes, and superconductor coil systems. Among the superconducting materials, particular attention was paid to the magnesium di-boride MgB2 and its potential applications in the power industry. The benefits of the use of carbon films with amorphous structures in electronics, sensing technologies, solar cells, FETs, and memory devices were discussed. The article provides the information about most interesting, from the R&D point of view, groups of materials for PV applications. It summarises the advantages and disadvantages of their use regarding commercial requirements such as efficiency, lifetime, light absorption, impact on the environment, costs of production, and weather dependency. Silicon processing, inkjet printing, vacuum deposition, and evaporation technologies that allow obtaining improved and strengthened materials for solar cell manufacturing are also described. In the case of the widely developed plasma generation field, waste-to-hydrogen technology including both thermal and non-thermal plasma techniques has been discussed. The review aims to draw attention to the problems faced by the modern power industry and to encourage research in this area because many of these problems can only be solved within the framework of interdisciplinary and international cooperation.
The current state of knowledge on the role of NKG2D ligands in multiple sclerosis and other autoimmune diseases
Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with demyelinating inflammatory characteristics. It is the most common nontraumatic and disabling disease affecting young adults. The incidence and prevalence of MS have been increasing. However, its exact cause remains unclear. The main tests used to support the diagnosis are magnetic resonance imaging (MRI) examination and cerebrospinal fluid (CSF) analysis. Nonetheless, to date, no sensitive or specific marker has been identified for the detection of the disease at its initial stage. In recent years, researchers have focused on the fact that the number of natural killer cell group 2 member D (NKG2D) family of C-type lectin-like receptor + (NKG2D+) T cells in the peripheral blood, CSF, and brain tissue has been shown to be higher in patients with MS than in controls. The activating receptor belonging to the NKG2D is stimulated by specific ligands: in humans these are major histocompatibility complex (MHC) class I polypeptide–related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) proteins and UL16 binding 1–6 proteins (ULBP1-6). Under physiological conditions, the aforementioned ligands are expressed at low or undetectable levels but can be induced in response to stress factors. NKG2D ligands (NKG2DLs) are involved in epigenetic regulation of their expression. To date, studies in cell cultures, animal models, and brain tissues have revealed elevated expression of MICA/B, ULPB4, and its mouse homolog murine UL16 binding protein-like transcript (MULT1), in oligodendrocytes and astrocytes from patients with MS. Furthermore, soluble forms of NKG2DLs were elevated in the plasma and CSF of patients with MS compared to controls. In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.
Dietary Supplements with Proline—A Comprehensive Assessment of Their Quality
Dietary supplements are food products commonly used worldwide to obtain nutritional and physiological effects. They can contain a wide variety of active substances and can be administered for health and disease. Their use can be beneficial if justified, and their quality is adequate. Unfortunately, data on the quality of supplements is scarce. As part of this work, we assess the quality of seven dietary supplements containing proline. The preparations were produced in the EU and the USA. The quality assessment consisted of the detection of potential impurities, the determination of the content of the main ingredient, and the release of proline. The technique used to analyse impurities and proline (Pro) content was liquid chromatography coupled with tandem mass spectrometry. We detected five contaminants. The main ingredient content was in the range of 73–121% in capsules and 103–156% in tablets. Five of the seven analysed dietary supplements released below 80% Pro (for each tablet/capsule at pH 1.2). One of the supplements may be inactive because a very low release of Pro was reported. The results, we hope, will increase consumer awareness of the quality of these preparations and result in a change in the regulations governing the marketing of these preparations, at least by making release testing mandatory.