Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing–remitting multiple sclerosis patients, aged 18–50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 mg (three times weekly) for 12 months, were randomized to combination therapy (interferon+atorvastatin 20mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n 1⁄4 21) or B (n 1⁄4 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p 1⁄4 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p 1⁄4 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone

12-months prospective Pentraxin-3 and metabolomic evaluation in multiple sclerosis patients treated with glatiramer acetate

Background: Pentraxin-3 (PTX-3) is involved in acute immunological responses and it is a pro-inflammatory protein and a novel biomarker of inflammatory diseases. It is demonstrated that PTX-3 is higher in cerebrospinal fluid (CSF) of aggressive Multiple Sclerosis (MS). Metabolomics, the identification of small endogenous molecules, offers a molecular profile of MS. Glatiramer acetate (GA) is a widely used treatment for (MS) but its mechanism of action is not completely defined. The aim of our study is to analyze PTX-3 and metabolomic profile in MS patients compared to controls and to investigate the effect of GA on PXT-3 and metabolic molecules during treatment in responder and not responder MS patients. Methods: 28 unrelated MS patients and 27 age-and sex-matched controls were recruited. In serum, PTX-3 levels were measured by ELISA and Metabolomic panel was evaluated trough Nuclear Magnetic Resonance (NMR). According to clinical practice patients started GA treatment; PTX-3 and metabolomic identification were performed before and during treatment. Responders to treatment were identified if no evidence of instrumental, clinical relapses and disability progression (NEDA) occurred during follow up. Results: Serum PTX-3 levels were higher in MS patients compared to matched controls (7,85 ± 2,19 vs 6,20 ± 1,63 ng/ml) (p = 0,03); metabolomic evaluation shows higher levels of lactate and lower levels of valine, tyrosine and tryptophan in MS patients compared to controls. During therapy, PTX-3 levels have been reduced statistically significant (p = 0,001) at six months and one year of treatment. After one year, of the twenty patients that completed the study, 55% were considered fully responders to treatment; in these patients the mean reduction of PTX-3 at one year was higher respect to not responders (−3,82 ± 1,24 ng/ml vs −2,32 ± 1,03 ng/ml p = 0,02) and we observed a higher reduction of lactate, tyrosine and hypoxanthine and an increase of hydroxyproline and ADP as well as of three oxidative phosphorylation markers, citrulline, ornithine and tryptophan approaching the metabolic profile of healthy subjects. Discussion and conclusions: We demonstrated a metabolomic imbalance with mitochondrial dysfunction detected by higher levels of lactate and lower levels of tryptophan, tyrosine and valine in MS patients compared to healthy controls. The reduction of PTX-3 levels and the restoring of mitochondrial function, reducing oxidative stress by GA, allows to identify responder patients. Further and larger studies are needed to understand the predictive role of PTX-3 and metabolomic pattern in the identification of responder patients to GA

Cloudlet architecture for dashboard in cloud and ubiquitous manufacturing

The aim of this paper is to present a cloudlet architecture for dashboard in Cloud and Ubiquitous Manufacturing. In practice means that, with Cloud Computing adoption, Manufacturing requires management applications where ubiquity and effectiveness are enabled. If ubiquity and resources scalability, availability and capacity can be well supported by cloud, pragmatics instruments are required to support effectiveness. The architecture here presented shows the integration of enriched existing (cloud) services, as instances of resources, with layers of new services towards direct and synchronous communication between users. These Rich Internet Application (RIA) components, here named cloudlets, integration, follow dashboards organization patterns and will be supported by emergent web3.0 interaction technologies. In fact, the paper proposes a new Presentation Layer to be used in UMS and (that may be used) in any multi-layer cloud-based web application. (C) 2013 Authors. Published by Elsevier B. V.The authors wish to acknowledge the support of: 1) The national Foundation for Science and Technology - FCT (Fundacao para a Ciencia e a Tecnologia) scholarship, reference number SFRH/BD/49540/2009, 2) The Foundation for Science and Technology - FCT, Project PTDC/EME-GIN/102143/2008, 'Ubiquitous oriented embedded systems for globally distributed factories of manufacturing enterprises', 3) EUREKA, Project E! 4177-Pro-Factory UE

A Cloud-Based Architecture with embedded Pragmatics Renderer for Ubiquitous and Cloud Manufacturing

The paper presents a Cloud-based architecture for Ubiquitous and Cloud Manufacturing as a multilayer communicational architecture designated as the Communicational Architecture. It is characterised as (a) rich client interfaces (Rich Internet Application) with sufficient interaction to allow user agility and competence, (b) multimodal, for multiple client device classes support and (c) communicational to allow pragmatics, where human-to-human real interaction is completely supported. The main innovative part of this architecture is sustained by a semiotic framework organised on three main logical levels: (a) device level, which allows the user `to use' pragmatics with the system, (b) application level which results for a set of tools which allows users pragmatics-based interaction and (c) application server level that implements the Pragmatics renderer,a pragmatics supporting engine that supports all pragmatics services. The Pragmatics renderer works as a communication enabler, and consists of a set of integrated collaboration technology that makes the bridge between the user/devices and the `system'. A federated or community cloud is developed using a particular cloud REST ful Application Programming Interface that supports (cloud) services registration, composition and governance (pragmatics services behaves as SaaS in the cloud).The work is supported by the Portuguese National Funding Agency for science, research and technology (FCT), (1) Grant No. UID/CEC/00319/2013, and (2) `Ph.D. Scholarship Grant' reference SFRH/BD/85672/2012.info:eu-repo/semantics/publishedVersio

Identification of Phytoplankton Blooms under the Index of Inherent Optical Properties (IOP Index) in Optically Complex Waters

[EN] Phytoplankton blooms are sporadic events in time and are isolated in space. This complex phenomenon is produced by a variety of both natural and anthropogenic causes. Early detection of this phenomenon, as well as the classification of a water body under conditions of bloom or non-bloom, remains an unresolved problem. This research proposes the use of Inherent Optical Properties (IOPs) in optically complex waters to detect the bloom or non-bloom state of the phytoplankton community. An IOP index is calculated from the absorption coefficients of the colored dissolved organic matter (CDOM), the phytoplankton (phy) and the detritus (d), using the wavelength (lambda) 443 nm. The effectiveness of this index is tested in five bloom events in different places and with different characteristics from Mexican seas: 1. Dzilam (Caribbean Sea, Atlantic Ocean), a diatom bloom (Rhizosolenia hebetata); 2. Holbox (Caribbean Sea, Atlantic Ocean), a mixed bloom of dinoflagellates (Scrippsiella sp.) and diatoms (Chaetoceros sp.); 3. Campeche Bay in the Gulf of Mexico (Atlantic Ocean), a bloom of dinoflagellates (Karenia brevis); 4. Upper Gulf of California (UGC) (Pacific Ocean), a diatom bloom (Coscinodiscus and Pseudo-nitzschia) and 5. Todos Santos Bay, Ensenada (Pacific Ocean), a dinoflagellate bloom (Lingulodinium polyedrum). The diversity of sites show that the IOP index is a suitable method to determine the phytoplankton bloom conditions.CONACYT supported this research with a doctorate scholarship to Jesús A. Aguilar-Maldonado, with the announcement number 251025 in 2015. María-Teresa Sebastiá-Frasquet was a beneficiary of the BEST/2017/217 grant, supported by the Valencian Conselleria d Educació, Investigació, Cultura i Esport (Spain) during her stay at the Universidad Autónoma de Baja California (Mexico). 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Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable tracker study

BackgroundSleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression. ObjectiveTo evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis. MethodsThis was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (n=177) or beta interferon (n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored. ResultsPatients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (p&lt;0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life. ConclusionIn patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate

Cd19 cell count at baseline predicts b cell repopulation at 6 and 12 months in multiple sclerosis patients treated with ocrelizumab

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics. Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation rate (FR) and those with slow repopulation rate (SR). Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0,008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six-and twelve-month follow-ups, respectively). Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients

Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine

Introduction Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment.Methods We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures.Results 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy.Discussion Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding