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Background Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST). Objectives To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex® treatment. Methods Ten MS patients with spasticity ('cases') underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline. Results At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT ( P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex® resulted in a reduction of NRS for spasticity ( P=.01). Conclusions We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex® clinical effect. [ABSTRACT FROM AUTHOR]

Background Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST). Objectives To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex® treatment. Methods Ten MS patients with spasticity ('cases') underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline. Results At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT ( P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex® resulted in a reduction of NRS for spasticity ( P=.01). Conclusions We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex® clinical effect. [ABSTRACT FROM AUTHOR]

Background: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria., Methods: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m 2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores., Results: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m 2 . Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤  - 2 at any site, was 15%. Average Z-scores were negative across most sites., Conclusions: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Cystinuria (CYS) is the most common monogenic kidney stone disease., Methods: Starting from an unusual case of CYS associated to primary sclerosing cholangitis, inflammatory bowel disease (IBD), and autoimmune hepatitis in a young male, we carefully review the literature and propose here a working hypothesis regarding the potential risk of cystinuric patients to develop conditions due to immune system dysregulation. To corroborate this hypothesis, we retrospectively evaluate the frequency of dysimmunity in a monocentric cohort including 36 cystinuric patients compared to healthy and disease controls., Results: CYS patients have an increased prevalence of atopic disease compared to disease controls (p = 0.03) and 16.7% of CYS subjects were diagnosed with allergic disease to a variety of antigens., Conclusion: Further studies are needed to define the relationship between proximal tubular transport defect of CYS and dysregulated immunity., (© 2024 S. Karger AG, Basel.)

This data article describes a new dataset on product-level trade elasticity, here defined as the degree of substitutability between varieties, i.e. between products exported by different countries into a given destination. The dataset contains trade elasticities for a list of more than 5000 products of the HS 6-digit classification. Trade elasticities computed using alternative sector classifications are provided as well (TIVA, GTAP, WIOD classification), by pooling the product-level observations within each sector. Starting from the prior that the coefficient associated with tariffs - a variable trade cost - corresponds to the import-demand elasticity in a standard CES structural gravity model of bilateral trade, elasticities are recovered from country-pair specific information on applied tariffs and trade. For each HS 6-digit product category we observe the universe of bilateral trade flows between countries, in value, in a given year, and the tariff (preferential or not) applied to each exporter by each importer on the specific product for 2001, 2004, 2007, 2010, 2013 and 2016. The tariff elasticity is (minus) the elasticity of substitution across products coming from different origins. Product-specific trade elasticity estimations are crucial for the evaluation of the welfare consequences of trade policies, and for the comparison of the welfare gains from trade for countries at different level of development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Trichinellosis is a zoonotic disease due to the ingestion of raw or undercooked meat from animals infected with the larvae of nematodes belonging to the genus Trichinella. In January-February 2015, an outbreak of trichinellosis occurred in Genoa, Northern Italy. The epidemiological link was traced back to a dinner served at an agritourism farm on 31 December 2014, where a majority of the 52 guests had consumed the 'beef' steak tartare. The source of infection was not traced; however, it was noted that the amount of beef purchased officially for providing at the dinner did not correspond with that served, suggesting that meat of a different origin had been added to the beef to prepare the steak tartare. Clinical and laboratory data of 30 individuals out of the 52 (57.7%), of which four were hospitalized, were consistent with that of the case definition of trichinellosis. Western blot patterns of the sera from patients with confirmed trichinellosis were similar to the diagnostic pattern identified for the reference sera of Trichinella pseudospiralis but different from those of the control sera tested for patients infected with Trichinella spiralis and Trichinella britovi. Identification of T. pseudospiralis as the aetiological agent responsible for the outbreak of trichinellosis using an indirect tool represents an advancement in the epidemiological investigation of this zoonotic disease., (© 2020 The Authors. Zoonoses and Public Health published by Wiley-VCH GmbH.)

Cortical lesions represent a hallmark of multiple sclerosis and are proposed as a predictor of disease severity. microRNAs are suggested to be important players in the disease pathogenesis and the experimental autoimmune encephalomyelitis animal model. We implemented a mouse model recapitulating more closely the human pathology as it is characterized by both an autoimmune heterogeneity and the presence of cortical lesions, two parameters missing in experimental autoimmune encephalomyelitis. In our model, mice clustered in two groups displaying high or low clinical scores. Upon cortical cytokine injection, lesions appeared with a specific topography while cortical miRNA profiles were altered. These two features differed according to disease severity. We evidenced changes in miRNA regulators and targets suggesting that miRNA alteration had functional repercussions that could explain the differences in cortical lesions. This model represents a crucial tool for the study of both miRNA involvement and cortical lesion formation in disease pathogenesis., Competing Interests: NO, OG, RC, PB, PH, MC, GO, MA, GM No competing interests declared, (© 2020, Orefice et al.)

HLA gene expression has an important role in the autoimmune disease predisposition. We investigated the mRNA expression profile of the risk alleles HLA-DRB1*15 and HLA-DRB1*13 in a cohort of subjects both multiple sclerosis (MS) patients and healthy controls. Moreover, we explored the expression of the allele HLA-DRB1*11 that is very frequent in our cohort from southern Italy. We found that the expression of MS-associated alleles in heterozygous MS patients was always higher than the nonassociated alleles. The differential risk allele expression occurred also in nonaffected subjects, though with a lower increment compared to MS patients., (© 2019 John Wiley & Sons Ltd.)

Recent studies showed that multiple sclerosis (MS) patients might experience communicative deficits, specifically in pragmatics (i.e., the ability to integrate the context-dependent aspects of language). A crucial region for pragmatics is the temporo-parietal junction, in particular the so-called Geschwind's area (GA), which is involved in high-level language processes, including the comprehension of narratives, metaphor, and irony. We evaluated the relationship between pragmatic abilities, measured through the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) test, and the functional connectivity (FC) of the bilateral GAs, assessed through a seed-based analysis of Resting-State fMRI in patients with MS. A positive correlation was observed between APACS scores and the FC for both the right and the left GA and the paracingulate cortex. Our findings suggest that the brain FC for social communication involves connections extending over both hemispheres, including right and left GAs and right and left paracingulate cortex, possibly impaired in patients with MS. This study offers preliminary evidence for future researches enrolling also a control sample to explore the involvement of GA in pragmatics in neurological disorders as well as in healthy conditions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To verify possible relations between vocal disability and aerodynamic measures in selected Parkinson's disease (PD) patients with low/moderate-grade dysphonia., Methods: Fifteen idiopathic dysphonic PD male patients were examined and compared with 15 euphonic subjects. Testing included the following measures: Voice Handicap Index (VHI), maximum phonation time (MPT), mean estimated subglottal pressure (MESGP), mean sound pressure level (MSPL), mean phonatory power (MPP), mean phonatory efficiency (MPE) and mean phonatory resistance (MPR)., Results: Statistical analysis showed: a significant reduction in MPR and MSPL in PD subjects compared to the healthy ones; a significant positive correlation between VHI score and MSPL, MPR, MPP, MESGP and a significant negative correlation between VHI and MTP within PD subjects. Test for multiple linear regression showed a significant correlation between VHI score, MPT, MPR and MSPL., Conclusions: A relationship between VHI and aerodynamic measures was shown in the present study. Compensatory mechanisms may aggravate vocal disability in PD subjects.

Objective: Cognitive functions have been largely investigated in multiple sclerosis. Less attention has been paid to social communication abilities, despite their presumptive affect on quality of life. We run the first comprehensive assessment of pragmatic skills in multiple sclerosis, evaluating also the relationship between pragmatics and other cognitive domains., Methods: Forty-two multiple sclerosis patients and 42 controls were tested for pragmatic abilities, neuro-cognition, social cognition, depression, and fatigue., Results: Patients performed poorly in most pragmatic tasks compared to controls. Globally, 55% of patients performed below the 5th percentile in the total pragmatic score. Notably, pragmatic skills did not differ between cognitively impaired and unimpaired patients. However, an association was found between pragmatics and verbal fluency, as measured in the Word List Generation. Finally, we observed an association of pragmatic abilities with social cognition, and a trend with psychosocial functioning., Conclusion: Overall, the study shows a diffuse pragmatic impairment in multiple sclerosis, not associated with the patient's global neuropsychological profile. By contrast, our findings suggest a close relation between pragmatics and specific cognitive aspects such as executive functions, and between pragmatics and social cognition. This study underlines the need of looking beyond classical cognitive performance, to consider underestimated communicative disturbances of high clinical relevance., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression., Methods and Results: In this report, we observed that extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), indicators of glycolysis and oxidative phosphorylation, respectively, were impaired during T cell activation in naïve-to-treatment relapsing remitting (RR)MS patients when compared with healthy controls. These results were also corroborated at biochemical level by a reduced expression of the glycolitic enzymes aldolase, enolase 1, hexokinase I, and by reduction of Krebs cycle enzymes dihydrolipoamide-S-acetyl transferase (DLAT) and dihydrolipoamide-S-succinyl transferase (DLST). Treatment of RRMS patients with interferon beta-1a (IFN beta-1a) was able to restore T cell glycolysis and mitochondrial respiration as well as the amount of the metabolic enzymes to a level comparable to that of healthy controls. These changes associated with an up-regulation of the glucose transporter-1 (GLUT-1), a key element in intracellular transport of glucose., Conclusions: Our data suggest that T cells from RRMS patients display a reduced engagement of glycolysis and mitochondrial respiration, reversible upon IFN beta-1a treatment, thus suggesting an involvement of an altered metabolism in the pathogenesis of MS., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mechanical ventilation is a cornerstone of the intraoperative management of the surgical patient and is still mandatory in several surgical procedures. In the last decades, research focused on preventing postoperative pulmonary complications (PPCs), both improving risk stratification through the use of predictive scores and protecting the lung adopting so-called protective ventilation strategies. The aim of this review was to give an up-to-date overview of the currently suggested intraoperative ventilation strategies, along with their pathophysiologic rationale, with a focus on challenging conditions, such as obesity, one-lung ventilation and cardiopulmonary bypass. While anesthesia and mechanical ventilation are becoming increasingly safe practices, the contribution to surgical mortality attributable to postoperative lung injury is not negligible: for these reasons, the prevention of PPCs, including the use of protective mechanical ventilation is mandatory. Mechanical ventilation should be optimized providing an adequate respiratory support while minimizing unwanted negative effects. Due to the high number of surgical procedures performed daily, the impact on patients' health and healthcare costs can be relevant, even when new strategies result in an apparently small improvement of outcome. A protective intraoperative ventilation should include a low tidal volume of 6-8 mL/kg of predicted body weight, plateau pressures ideally below 16 cmH2O, the lowest possible driving pressure, moderate-low PEEP levels except in obese patients, laparoscopy and long surgical procedures that might benefit of a slightly higher PEEP. The work of the anesthesiologist should start with a careful preoperative visit to assess the risk, and a close postoperative monitoring.

Background: Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST)., Objectives: To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex ® treatment., Methods: Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline., Results: At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex ® resulted in a reduction of NRS for spasticity (P=.01)., Conclusions: We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex ® clinical effect., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Multiple Sclerosis is a heterogeneous disorders involving in early stage gait and balance. Together with immunomodulating therapies, rehabilitation had a crucial role in improving motor tasks and quality of life. Between the emerging techniques, Focal Vibrations (FV) could play a role, but they have been used in MS only to reduce muscle tone and fatigue alone or together with botulinum toxin., Objective: To assess whether FV is effective on walking impairment in a cohort of MS patients., Methods: We performed a single-centre randomized, double-blind, sham-controlled study to investigate efficacy of FV vs sham vibration in 20 RR MS patients. Ten patients received treatment with the active device and ten patients sham treatment. Demographical, clinical and gait instrumental data analysis have been collected for each patient at baseline (T0), after treatment (T1) and after three weeks of wash out (T2)., Results: Both groups were clinically and demographically comparable. Treated patients showed significant improvements during the first right step (FRS) (p = 0.007), average stride lenght (ASL) (p = 0.012), double support right (DSRT) (p = 0.016) and left (DSLT) (p = 0.003) time. Non-treated patients didn't show any significance for any dynamic variables. Moreover, on posturographic measurements we registered only a trend towards significance in swing area with eyes open (SAEO) (p = 0.087). We also found in treated group significant improvements in FRT (p = 0.018); BBS (p = 0.037) and FSS scales (p = 0.038) between T1 and T0. Lastly, we found a significant inverse correlation in the treated group between disease duration and percentage of improvement for DSLT (r = - 0.775; p = 0.014) in T1 vs T0 and percentage of improvement of FSS, with an inverse correlation with both disease duration (r = - 0.775; p = 0.014) and AGE (r = - 0.733, p = 0.025) in T1 vs T0CONCLUSION: Our results suggest a beneficial effect of FV on walking impairment in MS patients suffering from spasticity and/or postural instability, which partially lasted until follow up.

Background: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis., Objectives: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis., Methods: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months., Results: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months., Conclusions: Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis., (© The Author(s), 2015.)

Objectives: Microalbuminuria (MAU) is associated with an enhanced risk of cardiovascular events. The prevalence of MAU and its prognostic impact has an important role in the stratification of cardiovascular risk in patients with essential hypertension. This is an observational, prospective study performed by 13 general practitioners aiming at assessing the prevalence and prognostic relevance of MAU in essential hypertension., Methods: Patients with essential hypertension and with recent determination of MAU were enrolled into the study by general practitioners, and were followed up for 3 years. Primary end point was the occurrence of major cardiovascular events during the follow-up., Results: Out of 1024 unselected patients, consecutively enrolled from January 2009 to March 2010, 804 completed the 3-year follow-up. Patients were categorized into two groups according to the absence (n = 523, 65%) or presence (n = 281, 35%) of MAU. During the follow-up, 41 cardiovascular events (1.69 events/100 patient-years) were reported. The presence of MAU was not associated with increased risk of cardiovascular events (adjusted hazard ratio = 1.32; 95% confidence interval 0.290-4.340, P = 0.097). When the analysis was restricted to the patients with previous cardiovascular event, MAU (adjusted hazard ratio = 2.18; 95% confidence interval 0.42-2.43, P = 0.031), together with age, metabolic syndrome, diabetes, and smoking, independently predicted the occurrence of cardiovascular events., Conclusion: Presence of MAU in patients with essential hypertension is not associated with increased risks of cardiovascular events. At the variance, in patients with previous cardiovascular events, MAU was found to predict recurrent events. Thus, the assessment of MAU could be considered a useful tool in secondary prevention.

Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-β1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebo-controlled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-β1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-β1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-β1a-related adverse effects in RR-MS.

This cross-sectional study has investigated the diagnostic and therapeutic management of patients suffering from multiple sclerosis (MS) in the Campania Region (Italy). A survey involving all the reference centers for MS in Campania Region was conducted from March to August 2011. Centers responded to a web-administered questionnaire on management and clinical characteristics of MS patients. In the study period, 3263 patients (mean age 37 years, 66 % females) accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9 %). About 37 % of the subjects without a previous diagnosis came to the centers on their own initiative. All patients underwent a complete neurological examination and expanded disability status scale. The other most common investigations were magnetic resonance imaging (44.0 %) and evoked potentials (22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs were interferon β and glatiramer acetate. The time between diagnosis and initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were under-used: 16 % of patients who might benefit from them show high clinical and radiological disease activity despite treatment with immunomodulant drugs. The MS care management of the surveyed centers showed consistent margins for improvement in 2011. Even though these data do not represent the current situation, they can be used to monitor improvements in MS care.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease leading to axonal injury. Even if the etiology of MS is still unknown the disease begins with inflammation involving autoreactive T lymphocytes activation in genetically susceptible subjects. Interferon beta-1b (IFN β 1b) is one of the most used drug in the MS therapy. The results obtained in this study show that the concentration of SOD1 in CSF of relapsing-remitting MS (RR-MS) patients, evaluated by enzyme-linked immunosorbent assay (ELISA), is decreased compared to pathological controls. Moreover, the Western blotting analysis demonstrated that SOD1 in human peripheral blood mononuclear cells (PBMC) in healthy controls was significantly higher compared to MS subjects before starting DMT therapy. In addition IFN β 1b therapy causes an increase of intracellular SOD1 protein as well as mRNA levels in PBMC. Moreover, the treatment of neuroblastoma SK-N-BE cells with IFN β 1b increased SOD1 protein and mRNA levels; these data also suggest that neuroprotective effect of this physiological molecule is, at least in part, carried out through its effect on SOD1. This study demonstrate that DMT therapy is able to increase SOD1 expression in PBMC of RR-MS patients. Therefore, the effectiveness of DMT therapy can be ascribed, at least in part, to an increased levels of this antioxidant enzyme as further confirmed by in vitro studies in SK-N-BE cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Whether the combination of chronic kidney disease (CKD) and left ventricular hypertrophy (LVH) affects the cardiovascular (CV) risk in patients with uncomplicated hypertension is poorly investigated. The aim of this study was to assess the effects of LVH, CKD, and their combination on CV events in hypertension., Methods: This study analyzed 1,078 patients with essential hypertension., Results: LVH was present in 104 (9.6%) patients, CKD was present in 556 (51.5%) patients, and the combination of LVH and CKD was found in 174 (16.1%) patients. During the follow-up (median = 84 months), 52 CV events were observed (0.64 events/100 patient-years): 6 (2.4%) in patients without target-organ damage (TOD), 6 (5.7%) in patients with LVH, 20 (3.6%) in patients with CKD, and 20 (11.4%) in patients with combined LVH+CKD. Adjusted hazard ratio (HR) for CV events was 1.62 (P = 0.34) for LVH, 0.951 (P = 0.94) for CKD, and 2.45 (P = 0.03) for LVH+CKD. After multivariable Cox proportional hazard analysis, the combination of LVH+CKD was significantly associated with risk of CV events, when the model was adjusted for sex and age (HR = 2.447; P = 0.03) and for the presence of 1 CV risk factor (HR = 3.226; P = 0.02). In contrast, the association of LVH+CKD was no longer significant when the model was adjusted for sex, age, and the presence of ≥ 2 CV risk factors., Conclusions: The results of this study highlight the relevance of the interactions between TODs and hemodynamic, anthropometric, and metabolic abnormalities in the CV risk stratification of patients with essential hypertension., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)