Progressive ms

OBJECTIVE: Primary progressive multiple sclerosis (PPMS) causes accumulation of neurologic disability from disease onset without clinical attacks typical of relapsing multiple sclerosis (RMS). However, whether genetic variation influences the disease course remains unclear. We aimed to determine whether mutations causative of neurologic disorders that share features with MS contribute to risk for developing PPMS. METHODS: We examined whole-genome sequencing (WGS) data from 38 PPMS and 81 healthy subjects of European ancestry...

Structural alterations in the cirrhotic heart may contribute to electromechanical abnormalities, represented by QT prolongation. The aim of this study was to investigate the changes in QTc according to the operative stage during pediatric LT and to identify which baseline echocardiographic parameters were associated with intraoperative QTc prolongation. Data were evaluated from 39 children undergoing LT for chronic liver disease (median age 9 months). In 19 patients (48.7%), baseline QTc was prolonged ≥440 ms (462 ± 19 ms)...

Multiple sclerosis is a chronic dysimmune neurodegenerative disease of the central nervous system, that affects people of working age and inevitably leads to disability. Treatment of the disease is one of the urgent problems of modern clinical neurology, which is explained by the variety of clinical variants of the flow, the lack of an effective method of treatment. This article is devoted to a review of modern approaches to the issues of etiology, pathogenesis and treatment of multiple sclerosis. Also, the classification of multiple sclerosis depending on the course of the disease, data on modern approaches to the treatment of multiple sclerosis, the criteria for the appointment of differentiated therapy depending on the course of the disease with the use of Disease-Modifying Drugs (DMDs) are given...

Human pluripotent stem cells (hPSCs) can be differentiated in vitro into cardiomyocytes (CMs) but the molecular mechanisms behind this process are still not fully understood. In particular identification of morphogens remained elusive because the mass spectrometry (MS)-based identification of secreted proteins from cell culture supernatants is impeded by high levels of albumin present in common differentiation media. Thus we established an albumin-free cardiomyogenic differentiation medium and performed secretomics at seven different time points during in vitro differentiation...

The data presented here are related to the research paper entitled "Metabolomic profiling suggests long chain ceramides and sphingomyelins as a possible diagnostic biomarker of epithelial ovarian cancer." (Kozar et al., 2018) [1]. Metabolomic profiling was performed on 15 patients with ovarian cancer, 21 healthy controls and 21 patients with benign gynecological conditions. HPLC-TQ/MS was performed on all samples. PLS-DA was used for the first line classification of epithelial ovarian cancer and healthy control group based on metabolomic profiles...

Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases...

Leukemia Inhibitory Factor (LIF) is a polyfunctional cytokine, involved in numerous regulatory effects in vivo and in vitro, varying from cell proliferation to differentiation, and has therapeutic potential for treating various diseases. In the current study, a COS-1 cell line overexpressing recombinant Buffalo LIF (rBuLIF) was established. The rBuLIF was purified to homogeneity from the total cell lysate of COS-1 cells using a two-step affinity chromatography. The purified LIF was confirmed by western blot and mass spectrometer (MS/MS)...

INTRODUCTION: Ocrelizumab is a humanised monoclonal antibody that targets the CD20 antigen on B cells. It has recently been approved by the US (Food and Drug Administration) and European health agencies (European Medicines Agency) for the treatment of multiple sclerosis (MS) and is the first drug marketed for both relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). The clinical trials conducted for both the relapsing forms (OPERA I/II) and the progressive forms of the disease (ORATORIO) have demonstrated its efficacy...

Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood...

Timeliness and accuracy in the diagnosis of microbial infections are associated with decreased mortality and reduced length of hospitalization, especially for severe, life-threatening infections. A rapid diagnosis also allows for early streamlining of empirical antimicrobial therapies, thus contributing to limit the emergence and spread of antimicrobial resistance. The introduction of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for routine identification of microbial pathogens has profoundly influenced microbiological diagnostics, and is progressively replacing biochemical identification methods...

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE)...

OBJECTIVES: Methadone is often used in pediatric patients to prevent or treat opioid withdrawal after prolonged sedation. Prolonged corrected QT interval is an important adverse effect of methadone because it can progress to torsades de pointes, a potentially fatal dysrhythmia. The prevalence of corrected QT interval prolongation and contributing risk factors are not well defined in hospitalized pediatric patients receiving methadone. The study purpose was to identify the frequency and risk factors of corrected QT interval prolongation in hospitalized pediatric patients receiving methadone...

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is commonly used by clinical microbiology laboratories to identify bacterial pathogens and yeasts, but not for the identification of moulds. Recent progress in extraction protocols and the composition of comparative libraries support potential application of MALDI-TOF MS for mould identification in clinical microbiology laboratories. We evaluated the performance of the Bruker Microflex™ MALDI-TOF MS instrument (Billerica, MA, USA) to identify clinical isolates and reference strains of moulds using three libraries, the Bruker mould library, the National Institutes of Health (NIH) library, and the Mass Spectrometry Identification (MSI) online library, and compared those results to conventional (morphological) and molecular (18S/ITS; gold standard) identification methods...

Significance: Better understanding of wound healing could lead to improved treatment(s) of multiple sclerosis (MS) and psoriasis (Pso). Recent Advances: New concepts in the events of wound healing, such as the roles of the innate and adaptive immune systems, have generated targets for treating these debilitating diseases. Innovation: That in MS and Pso defective wound healing is responsible for the diseases' progression has not been hypothesized to date. Conclusion: Impaired initiation of wound repair by oligodendrocyte precursor cells or oligodendrocytes may play a role in MS, and a lack of inhibition of the proliferative phase in wound healing may explain the pathophysiology involved in Pso...

MRI has a significant role in the diagnosis of multiple sclerosis. The newer and newer treatment options of the disease make it necessary to monitor the effectiveness of the therapy. Besides the clinical signs (clinical relapses and progression), the different MRI parameters can also reflect the disease activity. In our current article we summarize those MRI markers, which best predict the long-term disability, based on the international standards.

PURPOSE: The molecular underpinnings that may prognosticate survival and increase our understanding of tumor development and progression are still poorly understood. This study aimed to define the molecular signatures for malignancy in small cell lung carcinoma (SCLC), which is known for its highly aggressive clinical features and poor prognosis. EXPERIMENTAL DESIGN: Using clinical specimens, we performed a comparative proteomic analysis of high-grade SCLCs and low-grade pulmonary carcinoid tumors (PCTs), both of which are types of neuroendocrine tumors...

In vivo exploration of neurodegenerative diseases by positron emission tomography (PET) imaging has matured over the last 20 years, using dedicated radiopharmaceuticals targeting cellular metabolism, neurotransmission, neuroinflammation, or abnormal protein aggregates (beta-amyloid and intracellular microtubule inclusions containing hyperphosphorylated tau). The ability of PET to characterize biological processes at the cellular and molecular levels enables early detection and identification of molecular mechanisms associated with disease progression, by providing accurate, reliable, and longitudinally reproducible quantitative biomarkers...

A novel gas to particle conversion-gas exchange technique coupled with inductively coupled plasma mass spectrometry (GPD-GED-ICP-MS) was recently proposed for the direct analysis of ultra-trace levels of metallic compound gases such as metal carbonyl and semiconductor gases as well as gaseous mercury (Hg) in ambient air. These metallic compound gases should reveal reactivity with respect to ozone and gas to particle conversion could be obtained in a gas to particle conversion device (GPD) through metal oxides by oxidation...

The profiling of fatty acids (FAs) or sterols has been applied in clinical studies, but still needs to be improved to enable their simultaneous quantification. Moreover, little progress has been made in determining the levels of FAs and sterols in human saliva in a single run. In this study, gas chromatography-tandem mass spectrometry (GC-MS/MS) using one-step tert-butyldimethylsilyl (TBDMS) derivatization was developed for comprehensive profiling of 18 FAs (eight saturated, five monounsaturated, and five polyunsaturated FAs) and 7 sterols (cholesterol and its precursors)...

OBJECTIVE: To determine autonomic dysfunction (AD) differences in patients with relapsing remitting multiple sclerosis (pwRRMS) and progressive MS (pwPMS). METHODS: Composite autonomic scoring scale (CASS) and heart rate variability (HRV) were performed in 40 pwRRMS and 30 pwPMS. RESULTS: pwPMS had a significantly higher sudomotor index and total CASS score compared to pwRRMS (p < 0.001 and p < 0.001, respectively). Disease duration positively correlated with sudomotor index and total CASS (rs  = 0...