Fibromyalgia Syndrome (FMS) is a chronic disease characterized by widespread pain, and difficult to diagnose and treat. We analyzed the plasma metabolic profile of patients with FMS by using a metabolomics approach combining Liquid Chromatography-Quadrupole-Time Of Flight/Mass Spectrometry (LC-Q-TOF/MS) with multivariate statistical analysis, aiming to discriminate patients and controls. LC-Q-TOF/MS analysis of plasma (FMS patients: n = 22 and controls: n = 21) identified many lipid compounds, mainly lysophosphocholines (lysoPCs), phosphocholines and ceramides. Multivariate statistical analysis was performed to identify the discriminating metabolites. A protein docking and molecular dynamic (MD) study was then performed, using the most discriminating lysoPCs, to validate the binding to Platelet Activating Factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) Receptor (PAFr). Discriminating metabolites between FMS patients and controls were identified as 1-tetradecanoyl-sn-glycero-3-phosphocholine [PC(14∶0/0∶0)] and 1-hexadecanoyl-sn-glycero-3-phosphocholine [PC(16∶0/0∶0)]. MD and docking indicate that the ligands investigated have similar potentialities to activate the PAFr receptor. The application of a metabolomic approach discriminated FMS patients from controls, with an over-representation of PC(14∶0/0∶0) and PC(16∶0/0∶0) compounds in the metabolic profiles. These results and the modeling of metabolite-PAFr interaction, allowed us to hypothesize that lipids oxidative fragmentation might generate lysoPCs in abundance, that in turn will act as PAF-like bioactivators. Overall results suggest disease biomarkers and potential therapeutical targets for FMS.

Fibromyalgia (FM) is a central sensitization syndrome characterized by chronic widespread pain. FM is often comorbid with psychiatric disorders, as well as psychological distress that worsens the quality-of-life of people affected. The aim was to collect current evidence about the management of FM from a psychosomatic perspective. The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed; review articles, meta-analysis, overview, and guidelines published in the last 10 years written in English were included. Five main topics (Diagnostic criteria of FM; Pathogenesis of chronic widespread pain in FM; Early stress and trauma as predisposing factors for central sensitization; FM and Psychiatric comorbidity; Implications for treatment) were pointed out and discussed. Much evidence underlies the importance of considering and treating the comorbidity of FM with psychiatric disorders and psychological factors that affect pain management. Validation of FM as a central sensitization syndrome by a clinician facilitates therapeutic strategies that involve patients as active participants in the pain management process, likely leading to improved outcomes.

Background: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. Objective: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. Design: RCT with parallel and balanced large groups. Setting: Academic university hospital and Olympic gyms. Subjects: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. Methods: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of “life movements”, strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. Results: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). Conclusion: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes. Clinical Trials Registration No: NCT03858114

Fibromyalgia syndrome (FMS) is a complex illness to diagnose and treat, which presents symptoms that may be part of, or overlap with other diseases or syndromes.The most widely used diagnostic criteria are those of the American College of Rheumatology [1]; no laboratory test has been validated for FMS diagnosis which remains primarily clinically based.Oxidative stress has been proposed as a relevant event in the pathogenesis of FMS with an increase of lipid peroxidation (LPO) [2] and a decrease in vitamin A and E concentrations [3].Although the etiology of FMS remains unclear, genetic predisposition is likely to be an important factor and transmission is thought to be polygenic [4,5]. If FMS is a multi-genetic disease then it could be hypothesized that differences exist in the type of proteins or protein expression levels in sera of FMS patients compared with healthy controls.Proteomic analysis is a powerful tool for the global evaluation of protein expression and plays a central role in clinical diagnosis and monitoring. Some studies [6] reported interesting proteomic analysis data with an overexpression of transaldolase and phosphoglicerate mutase I in salivary fluid of FMS patients and focused on the role of oxidative stress in the pathogenesis of the disease.The aim of this preliminary study was to evaluate, using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), changes in protein profiles of FMS patients with respect to control subjects to identify potential serum biomarkers useful for disease diagnosis and management.Sixteen females (52 ± 12 years) affected by FMS and 12 healthy females (48 ± 13 years) were enrolled; all patients fulfilled new ACR diagnostic criteria [1] ( Table 1). The presence of a major clinical condition other than fibromyalgia was excluded by physical examination and routine blood and urine screening. No patients suffered of thyroid dysfunction. Psychiatric examination data of patients were reported in a previous study [7].Study was approved from our Local Ethical Committee and informed consent was obtained from all subjects.Serum protein concentrations were quantified using the PlusOne 2D Quant Kit (GE Healthcare); first dimension isoelectric focusing (IEF) was carried out with 18 cm immobilized pH gradient strips of pH 3-10. The IPG strips were applied onto 10% acrylamide sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) slab gels (25.5 cm × 20.5 cm × 1.0 mm) and overlaid with a solution of 0.5% agarose with a trace of bromophenol blue. Gels were fixed, stained with Coomassie Brilliant Blue G-250 colloidal for 24 h and stored at room temperature. At least three sample replicates were performed.2D data were processed with Progenesis SameSpots software, which computed multiplication fold, false discovery rate (FDR) q-value, p-values of all spots using one-way ANOVA analysis. A p-value < 0.05 was considered statistically significant; no difference has been found in protein expression according to patient therapy.After normalization, volume calcul...

FMS is a disorder that 'in itself' can have a devastating impact on an individual's life. The frequency of the association with major depressive and bipolar disorders increases the impact on the QoL of people with FMS. One of the causes of this association appears to be the extreme vulnerability to chronic stress that this disorder involves. The findings have important clinical significance: the physician must interpret in the right dimension and with dignity the suffering of the people with FMS.