178 research outputs found

    The relationship between self-efficacy and health-related quality of life in Multiple Sclerosis patients

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    Background and Objectives Multiple sclerosis (MS) has a broad spectrum of physical, social, psychological effects and significant impact on quality of life (QoL). Several studies has showed the importance of self-efficacy as a predictor of QoL in patients with MS.This study aims at evaluating the robustness of the relationship between self-efficacy and QoL. Specifically it aims to test whether such relation will vanish under the following conditions: using a general measure of self-efficacy and controlling for level of impairment defined as a broad construct dealing with physical, social and working changes due to the illness condition. Methods One hundred-fifty five participants responded to a questionnaire, including QoL and general self-efficacy measures, socio demographic and clinical variables. Two nested structural equation models that differ for the presence or absence of the path connecting self-efficacy and QoL was estimated.Results and Conclusions The hypothesis of the vanishing of the relationship between self-efficacy and QoL had to be rejected. These results support the genuineness of this relation and emphasize the importance of interventions promoting self-efficacy to improve QoL in chronic diseases such as MS. From a methodological perspective this study is an example of the usefulness of formative indicators in QoL studies

    Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells

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    Background: The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. Methods: We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty-five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart. Results: The NTZ-treated patients showed a lower percentage of CD62L (33.68 %, n = 113) than first-line treated patients (44.24 %, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 %; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08 %). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4+ T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4+ T cells. Conclusions: Our research confirms that NTZ has a specific effect on CD62LCD4+ T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ-treated patients. A larger study is required to better confirm the data

    Oxaprozin-Induced Apoptosis on CD40 Ligand-Treated Human Primary Monocytes Is Associated with the Modulation of Defined Intracellular Pathways

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    The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-κB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-κB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes

    1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

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    Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120–139 mg/dL, n = 710; 140–159 mg/dL, n = 912; 160–179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCgluc and AUCins progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCgluc decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion

    Successful pregnancy and disease outcomes in a NMOSD patient treated with tocilizumab

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    Abstract Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune relapsing disease involving the central nervous system with predominant inflammatory attack of optic nerves, spinal cord and area postrema, often leading to severe disability. Women with NMOSD typically experience adverse pregnancy outcomes and high relapse rates during pregnancy and the postpartum period. Case report Herein we present a case of pregnancy in a young NMOSD woman treated with tocilizumab. The course of her pregnancy was clinically unremarkable and treatment whit Tocilizumab was well tolerated. Conclusions This case raises the possibility that the modulation of immune system by inhibitors of the IL-6 pathway could a promising therapeutic option for pregnancy in NMOSD patient

    Vitamin D binding protein isoforms and apolipoprotein E in cerebrospinal fluid as prognostic biomarkers of multiple sclerosis

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    Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a heterogeneous and unpredictable course. To date there are no prognostic biomarkers even if they would be extremely useful for early patient intervention with personalized therapies. In this context, the analysis of inter-individual differences in cerebrospinal fluid (CSF) proteome may lead to the discovery of biological markers that are able to distinguish the various clinical forms at diagnosis.To this aim, a two dimensional electrophoresis (2-DE) study was carried out on individual CSF samples from 24 untreated women who underwent lumbar puncture (LP) for suspected MS. The patients were clinically monitored for 5 years and then classified according to the degree of disease aggressiveness and the disease-modifying therapies prescribed during follow up.The hierarchical cluster analysis of 2-DE dataset revealed three protein spots which were identified by means of mass spectrometry as Apolipoprotein E (ApoE) and two isoforms of vitamin D binding protein (DBP). These three protein spots enabled us to subdivide the patients into subgroups correlated with clinical classification (MS aggressive forms identification: 80%). In particular, we observed an opposite trend of values for the two protein spots corresponding to different DBP isoforms suggesting a role of a post-translational modification rather than the total protein content in patient categorization.These findings proved to be very interesting and innovative and may be developed as new candidate prognostic biomarkers of MS aggressiveness, if confirmed

    Beliefs, barriers and preferences of European overweight women to adopt a healthier lifestyle in pregnancy to minimize risk of developing gestational diabetes mellitus: an explorative study

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    Introduction: Overweight and obese women are at high risk of developing gestational diabetes mellitus (GDM). Lifestyle programs might help curb the GDM risk. We explored beliefs, perceived barriers and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future high quality lifestyle interventions. Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI≥25kg/m2). In three European countries (Belgium, Netherlands, United Kingdom) interviews were conducted, followed by questionnaires in six other European countries (Austria, Denmark, Ireland, Italy, Poland, Spain). Content analysis, descriptive and chi square statistics were applied (p&#60;0.05). Results: Women preferred to obtain detailed information about their personal risk. The health of their baby was major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women

    Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study

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    Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance. Methods: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at &lt; 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation. Results: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94. Conclusions: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research
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