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Magnetic resonance imaging (MRI) is an important paraclinical tool to diagnose and monitor multiple sclerosis (MS). Conventional MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques are improving the understanding of the mechanisms underlying tissue injury, repair, and functional adaptation in MS; however, they require careful standardization. The definition of standardized methods for the collection and analysis of advanced MRI techniques is central not only to improve the understanding of disease pathophysiology and evolution, but also to generate research hypotheses, monitor treatment, increase cost-effectiveness and power of clinical trials. We promoted the Italian Neuroimaging Network Initiative (INNI), involving centers and investigators with an International recognized expertise, with the major goal to determine and validate novel MRI biomarkers to be utilized as predictors and/or outcomes in future MS studies. The INNI initiative supported the creation of a centralized repository, where advanced structural and functional MRI scans available at the participating sites, with the related clinical and neuropsychological data, are collected. These data will be used to perform research studies to identify clinical, neuropsychological and imaging biomarkers characteristics of the entire spectrum of MS. INNI will be instrumental to help to define standardized MRI and clinical protocols towards an increasing uptake of personalized interventions for people with MS at a national and international level. Upon approval of the INNI Steering Committee, the data collected in the online database will be shared with any research center detailing specific research proposals on disease pathophysiology or treatment effects. [ABSTRACT FROM AUTHOR]

We study the dynamics of sea-spray particles in the coastal region of La Reunion Island on the basis of numerical simulations using the transport aerosol model MACMod (Marine Aerosol Concentration Model) and a survey of the aerosol size distributions measured at four locations at two different heights in the north-west part of the island. This allows evaluation of the performance of our model in case of pure marine air masses with implementation of accurate boundary conditions. First of all, an estimate of the aerosol concentration at 10-m height at the upwind boundary of the calculation domain is obtained using a revisited version of the MEDEX (Mediterranean Extinction) model. Estimates of the vertical profile of aerosol concentrations are then provided using aerosol data obtained at two different heights at the upwind boundary of the calculation domain. A parametrization of the vertical profiles of aerosol concentrations for maritime environment is proposed. The results are then compared to the vertical profiles of 0.532 $$\upmu $$ m aerosol particle extinction coefficient obtained from lidar data provided by the Cloud-Aerosol LIdar with Orthogonal Polarization (CALIOP) and also to the data provided by the Aerosol Robotic Network (AERONET). This allows validation of the complete vertical profiles in the mixed layer and shows the validity of satellite data for determination of the vertical profiles. Two kinds of simulation were made: one without a particle advection flux at the upwind boundary of the numerical domain, whereas the second simulation was made with a particle advection flux. In the first case, the influence of the distance to the shoreline on the local sea-spray dynamics is investigated. In the second set of simulation, the particles issued from the local production in the surf zone near the shoreline are mixed with aerosols advected from the remote ocean. A good agreement between the model calculations using our boundary conditions and the data was found. The present results then attest the ability of this kind of model, as a first approach to predicting the local transport of sea-spray particles in a pure marine environment. [ABSTRACT FROM AUTHOR]

Abstract: The vertical and horizontal transport of aerosols generated over the surf zone is discussed. Experimental data were collected during the second campaign of the Surf Zone Aerosol Experiment that took place in Duck NC (USA) in November 2007. The Empirical Orthogonal Function (EOF) method was used to analyze the vertical concentration gradients, and allowed separating the surf aerosols from aerosols advected from elsewhere. The numerical Marine Aerosol Concentration Model (MACMod) supported the analysis by confirming that the concentration gradients are more pronounced under stable conditions and that aerosol plumes are then more confined to the surface. The model also confirmed the experimental observations made during two boat runs along the offshore wind vector that surf-generated aerosols are efficiently advected out to sea over several tens of kilometers. [Copyright &y& Elsevier]

Abstract: A model for the aerosol transport in the lower atmosphere is of great interest for studies on air and water quality. One of the difficulties of such a model is to provide the accurate source terms. In particular, for maritime environment, the production of particles generated at the air–sea interface by breaking waves largely varies in time and space (Piazzola et al., 2009). More particularly, near the coastal zone, the sea-spray aerosol fluxes depend on the development of the wave field. The present paper proposes some improvement of the model MACMod, published by Tedeschi and Piazzola (2011), which is dedicated to the transport of aerosol particles in the marine atmospheric boundary layer (MABL). Taking benefit of the experimental campaign MIRAMER conducted in the French Mediterranean in 2008, a new sea-spray source function has been introduced in the latter version of the model MACMod. This consists in a revisited version of the whitecap dependant formulation established by Monahan et al. (1986). The simulations were then validated using aerosol size distributions recorded on board the ship “Atalante” for different wind speeds. Error calculations show a good performance of the model since it predicts the aerosol concentration to within a maximum factor of 3 for particle radii between 0.5 to 5μm. [Copyright &y& Elsevier]

Migraine is a neurologic disorder characterized by disabling attacks of throbbing headache with specific features and associated symptoms. Despite the recent discoveries in basic neurosciences, migraine pathophysiology is not completely understood. Nevertheless, in the last decades, advances in functional magnetic resonance imaging (fMRI) have significantly provided new insights into migraine mechanisms. Blood oxygen level dependent (BOLD) fMRI technique is the most commonly used method to explore brain function and connectivity due to high temporal and spatial resolution. The purpose of this review is to present a synthesis of recent BOLD-fMRI studies which have allowed us to elucidate the complex process involved in migraine pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract: The present paper deals with the implementation of the Marine Aerosol Concentration Model (MACMod) in a Mediterranean coastal area. MACMod is a 2D unsteady model dedicated to the atmospheric transport of marine aerosols in the Marine Atmospheric Boundary Layer (MABL). The model predictions were compared to aerosol size distributions measured during experimental campaigns conducted in the French coastal Mediterranean area, for various experimental conditions. The results show a good agreement between the model calculations and the experimental data. In addition, the influence of the main parameters governing the transport of sea-salts in the MABL in case of offshore winds is investigated using model calculations. In particular, our work allows quantification of decrease or increase in concentrations dependent on the thermal stability conditions (compared to neutral case). It is also found that the thermal stability has an increased effect for low wind speeds. The concentration at 10m height of submicron and supermicron aerosols show an opposite behavior with regard to the stability conditions, i.e., concentration of the former is increased for stable conditions, whereas it is decreased for the latter. When the wind speed exceeds 15ms−1, the thermal stability effect is lowered. [Copyright &y& Elsevier]

Abstract: A model for the spatial variation of aerosol concentrations and deposition along the coastal zone is of great interest for studies on air and water quality. In coastal areas, sea-spray aerosols generated at the sea surface by the interaction between wind and waves add to a continental contribution emitted from natural and/or anthropogenic sources. To include coastal effects in the model for the prediction of aerosol concentrations, Piazzola et al. (2003) developed the coastal Mediterranean aerosol model. The present paper deals with an extension of the Mediterranean coastal aerosol to a regional scale applied to the prediction of the sea surface flux deposition. This was achieved by the development of an automatic coupling process between the aerosol model and a regional meso-scale meteorological model which allows accounting for the details of the orography of the coast. The results show a non-homogeneous spatial coverage of aerosol concentrations over the northwestern Mediterranean. The simulations were then validated using aerosol size distributions recorded on board the ship “Atalante” for two kinds of meteorological conditions. Error calculations show a good performance of the coupling process since it predicts the aerosol concentration to within a maximum factor of 3 for particle radii between 0.1 to 10µm. This process was then used to provide the spatial distribution of the particle deposition fluxes over the study area. [Copyright &y& Elsevier]

Background and purpose: Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. Patients and methods: About 195 cognitively unimpaired MS patients (150 relapsing–remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients’ anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance. Results: Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients. Conclusions: The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

In this paper we develop an order driver market model with heterogeneous traders that imitate each other on different network structures. We assess how imitations among otherway noise traders, can give rise to well known stylized facts such as fat tails and volatility clustering. We examine the impact of communication and imitation on the statistical properties of prices and order flows when changing the networks’ structure, and show that the imitation of a given, fixed agent, called “guru", can generate clustering of volatility in the model. We also find a positive correlation between volatility and bid-ask spread, and between fat-tailed fluctuations in asset prices and gap sizes in the order book. [ABSTRACT FROM AUTHOR]

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression. [ABSTRACT FROM AUTHOR]

Dementia is a common and growing problem, with 20% of those over 80 years of age suffering from this disorder. The prospect of more effective treatments has caused an increasing demand for a more accurate and earlier diagnosis of different dementia syndromes. Neuroimaging techniques may have an important role in the clinical evaluation of dementia for early diagnosis, differential diagnosis and may help in the prediction of conversion to dementia in individuals at a higher risk of developing the disorder. Moreover, new MRI techniques might not only further broaden our understanding of the pathophysiology but also accelerate treatment discovery. This review will focus on the use of conventional and non-conventional MRI techniques to investigate dementias. [ABSTRACT FROM AUTHOR]

Disease-modifying drugs (DMD) are effective in reducing relapses and magnetic resonance imaging (MRI) lesions in multiple sclerosis (MS). Nevertheless, individual treatment responses are variable, and accurate and reliable methods to identify DMD responsiveness have not been validated. Although extremely relevant in the study and management of MS, MRI data have not been systematically tested to answer this question yet. Here we present non-conventional MRI data, including magnetisation transfer imaging (MTI), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (1HMRS). As these techniques are more sensitive to microstructural tissue changes and more specific for the heterogeneous pathological substrates of MS lesions, we anticipate their potential role for detecting relevant changes of tissue pathology during treatment of MS patients and, consequently, for a better definition of response status to therapy. [ABSTRACT FROM AUTHOR]

A detailed analysis is made of some typical strong wind situations near the French Mediterranean coast. Special attention has been paid to the wind from the north-northwest in the Gulf of Lion, also called the mistral. The analysis is made from both the synoptic and mesoscale point of view with the aid of numerical simulations carried out with the Regional Atmospheric Modeling System (RAMS) to study the main atmospheric, climatic, and meteorological characteristics of this wind in the Gulf of Lion. Simulations were made with this model during the periods of 20–22 March and 24–26 March 1998. Afterward, a comparison was made with the meteorological measurements collected during the international Flux, Etat de la Mer et Télédétection en Condition de Fetch Variable (FETCH) campaign (Gulf of Lion, March–April 1998). The comparison between the simulated wind fields and the values measured by the coastal meteorological stations, an oceanographic buoy, and the ship Atalante at sea help to give full understanding of the complicated physical processes that characterize strong wind situations in coastal zones. [ABSTRACT FROM AUTHOR]

The article focuses on the analytical psychotherapy of schizophrenic patients. According to the author the psychotherapy of schizophrenia is an interesting field still full of open questions. It throws light on fundamental human problems. It leads one to reconsider the clinical methods and the whole question of human fate. It permits one to observe at close quarters some mental mechanisms and therapeutic problems that are present in less severe degrees and on less deep levels in the neuroses and in a more general sense it illustrates the development of psychic life in its archaic, unconscious aspects. It is in the psychotherapy of schizophrenia that the search for a standard therapeutic technique is refuted and proved to be an illusion.

the end of 2006, a pharmacovigilance program on natalizumab was settled by the Italian Pharmaceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was documented. [ABSTRACT FROM AUTHOR]

At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated. [ABSTRACT FROM AUTHOR]

Abstract The aim of this paper is to determine an accurate formulation for the sea-spray source function characteristic for the North-Western Mediterranean. To this end, the MACMod aerosol transport model was implemented in the study area using different sea-state dependent flux formulations. The simulations were compared to a large data set of aerosol size distributions acquired over the last ten years in the study area, yielding the evolution of the sea-spray concentrations with increasing fetch and hence, with the development of the wave field. This allowed for an improvement of the Demoisson et al. (2013) sea-spray source function (S3F) for the Mediterranean. The new formulation extends its validity to shorter fetch and larger radii and turned out to be most suitable for predicting the atmospheric concentrations of sea-spray aerosols in this region. Highlights • This paper deals with the study of the sea-spray contribution to the atmospheric aerosol in the North-Western Mediterranean. • The objective is the determination of an accurate sea-spray-source function in the 0.5–20 μm size range. [ABSTRACT FROM AUTHOR]

Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx. In this narrative review, we provide an overview of DTx in the care of patients with neurological dysfunctions. [ABSTRACT FROM AUTHOR]

Spinal cord imaging in amyotrophic lateral sclerosis: historical concepts - novel techniques. Integrated magnetic resonance imaging and [11 C]-PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis. 1 Bashford J, Mills K, Shaw C. The evolving role of surface electromyography in amyotrophic lateral sclerosis: a systematic review. Comparison of Two Clinical Upper Motor Neuron Burden Rating Scales in ALS Using Quantitative Brain Imaging. [Extracted from the article]

This study investigated the effect of 4-d acute thermal treatments at 18 °C, 26 °C (control) and 34 °C on the nervous system of adult zebrafish (Danio rerio) using a multidisciplinary approach based on behavioural tests and brain proteomic analysis. The behavioural variations induced by thermal treatment were investigated using five different tests, the novel tank diving, light and dark preference, social preference, mirror biting, and Y-Maze tests, which are standard paradigms specifically tailored for zebrafish to assess their anxiety-like behaviour, boldness, social preference, aggressiveness, and explorative behaviour, respectively. Proteomic data revealed that several proteins involved in energy metabolism, messenger RNA translation, protein synthesis, folding and degradation, cytoskeleton organisation and synaptic vesiculation are regulated differently at extreme temperatures. The results showed that anxiety-like behaviours increase in zebrafish at 18 °C compared to those at 26 °C or 34 °C, whereas anxiety-related protein signalling pathways are downregulated. Moreover, treatments at both 18 °C and 34 °C affect the exploratory behaviour that appears not to be modulated by past experiences, suggesting the impairment of fish cognitive abilities. This study is the continuation of our previous work on the effect of 21-d chronic treatment at the same constant temperature level and will enable the comparison of acute and chronic treatment effects on the nervous system function in adult zebrafish. [ABSTRACT FROM AUTHOR]

Introduction: Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time.Methods: Fifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up.Results: Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up.Conclusion: In early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening. [ABSTRACT FROM AUTHOR]

Introduction: The Fatigue Severity Scale (FSS-9) and the Parkinson Fatigue Scale (PFS-16) are commonly used for assessing fatigue in Parkinson's disease (PD). Here we validated the Italian version of these scales, assessed their psychometric properties by Rasch analysis, and computed their optimal cut-off scores using clinical diagnosis of PD-related fatigue as the gold standard.Methods: PD patients (n = 167) completed the Italian versions of FSS-9 and PFS-16. Each item of PFS-16 was scored both on a 5-point (PFS-16polytomous) and on a 2-point scale (PFS-16dichotomous).Results: All scales showed an adequate overall Rasch model fit, high reliability, and good discriminant, convergent, and concurrent validity, but were less accurate in measuring very high and very low fatigue levels. No evidence of differential item functioning with respect to age, sex, and severity of parkinsonian symptoms was found. Some items of FSS-9 (item 1), PFS-16polytomous (items 1 and 13), and PFS-16dichotomous (items 1, 8, and 13) showed misfit, possibly due to their content concerning sleep and motivation disorders. When FSS-9 and PFS-16polytomous' responses were rescored on a 3-point scale, the discriminability across response categories improved. The optimal cut-off score in detecting clinically-diagnosed fatigue (observed in 20% of the sample) was 3.09 for PFS-16polytomous, 8.00 for PFS-16dichotomous, and 4.67 for FSS-9.Conclusions: The Italian version of PFS-16 and FSS-9 showed sound psychometric properties and can be confidently used to quantify fatigue symptoms in PD, although clinical diagnosis of fatigue should rely on validated criteria. The PFS-16polytomous exhibited advantages with respect to PFS-16dichotomous. [ABSTRACT FROM AUTHOR]

Background: Little is known about the influence of multiple sclerosis (MS) diagnosis on parenthood attitude in people with MS (pwMS).Objective: To investigate the impact of diagnosis, clinical features and external disease-related influences on parenthood decision-making in Italian pwMS.Methods: A web-based survey was posted on SMsocialnetwork.com to investigate clinical status, parenthood desire, influences on family planning, pregnancy outcomes, abortions and adoptions of pwMS.Results: 33/395 respondents never wanted to become parent because of MS ("anti-parenthood after diagnosis"). 362 declared to be in favor of parenthood. 51% pwMS having a child by the survey time had already received the MS diagnosis at first childbirth. The frequency of a second child in pwMS after diagnosis was 38% compared to 67% in people without yet MS diagnosis. 16% of pwMS were discouraged to become parent after diagnosis, mainly by medical personnel. In 71% of respondents, diagnosis did not delay the decision to become parent and only 39% were counseled by treating physician to plan pregnancy. Patients' distribution according to the clinical phenotype (exclusively relapsing vs exclusively progressive) showed a higher proportion of progressive patients in the "anti-parenthood after diagnosis" subgroup.Conclusion: MS diagnosis impacted dramatically on the life project of 7% of pwMS that decided not to have children because of the disease and in pro-parenthood pwMS impacted especially on having the second child. Only a minority was counseled to plan pregnancy. A worse disease course driving to a progressive phenotype at survey time might have negatively impacted on parenthood desire. [ABSTRACT FROM AUTHOR]

Background: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS).Objectives: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF.Materials and methods: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days.Results: A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group.Conclusions: In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome.Methods: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects.Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation.Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients.Clinical Trial Registration: NCT02141607. [ABSTRACT FROM AUTHOR]

Introduction: Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.Methods: Eighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.Results: Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), "episodic anxiety" subscale of PAS (p = 0.005), and "cognitive apathy" subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).Conclusion: In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background and purpose In multiple sclerosis ( MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state ( RS) functional connectivity ( FC) changes of the default mode network ( DMN), salience network ( SN) and executive control network ( ECN) were assessed in a group of depressed MS (D- MS) patients and in appropriately matched control groups. Methods Sixteen D- MS patients, 17 non-depressed MS ( ND- MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. Results Comparing D- MS patients with D-S, within the DMN, a significant RS- FC suppression was found in the posterior cingulate cortex ( PCC); comparing D- MS with ND- MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D- MS patients compared to D-S and to ND- MS; within the ECN increased FC in the right inferior parietal cortex was found in D- MS patients compared to ND- MS patients. Conclusions In cognitively preserved D- MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS. [ABSTRACT FROM AUTHOR]

Objective The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory ( STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis ( MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects. Material and methods The STAI-Y-1 and STAI-Y-2 was completed by a group of patients ( n = 175) affected by MS and a group of healthy subjects ( n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale. Results There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2. Conclusions The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing–remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. Methods: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. Results: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. Conclusions: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains. [ABSTRACT FROM AUTHOR]

Aerosol particles in coastal areas result from a complex mixing between sea spray aerosols locally generated at the sea surface by the wind-waves interaction processes and a continental component resulting from natural and/or anthropogenic sources. This paper presents a physical and chemical analysis of the aerosol data acquired from May to September 2014 in the Adriatic Sea. Aerosol distributions were measured on the Acqua Alta platform located 15 km off the coast of Venice using two Particle Measuring System probes and a chemical characterization was made using an Ion Chromatography analysis (IC). Our aim is to study both the sea-spray contribution and the anthropogenic influence in the coastal aerosol of this Mediterranean region. To this end, we focus on a comparison between the present data and the aerosol size distributions measured south of the French Mediterranean coast. For air masses of marine origin transported by southern winds on the French coast and by the Sirocco in the Adriatic, we note a good agreement between the concentrations of super-micrometer aerosols measured in the two locations. This indicates a similar sea surface production of sea-spray aerosols formed by bubble bursting processes in the two locations. In contrast, the results show larger concentrations of submicron particles in the North-Western Mediterranean compared to the Adriatic, which result probably from a larger anthropogenic background for marine conditions. In contrast, for a coastal influence, the chemical analysis presented in the present paper seems to indicate a larger importance of the anthropogenic impact in the Northern Adriatic compared to the North-Western Mediterranean. [ABSTRACT FROM AUTHOR]

Background and purpose Depression is the most common psychiatric disorder in multiple sclerosis (MS). Self-report depression scales are frequently used as screening, diagnostic and grading instruments. This study investigated the psychometric properties of the Beck Depression Inventory second edition (BDI-II) for assessing depressive disorders in a sample of Italian MS patients. Methods The sample included 141 consecutive non-demented MS patients who completed the BDI-II and the Chicago Multiscale Depression Inventory (CMDI). MS patients also completed a clinical interview, a neurological/neuropsychological examination and a Fatigue Severity Score (FSS) questionnaire in order to assess divergent validity. Results The BDI-II showed good internal consistency (Cronbach's alpha 0.89) and good convergent and divergent validity. With respect to CMDI serving as the 'gold standard', the receiver operating characteristic curve revealed that BDI-II is an adequate diagnostic measure and that the optimum total cut-off score was 18.5. Such score identified clinically relevant depressive symptoms in 25.5% of our MS sample. Conclusions The BDI-II is a simple, reliable and valid tool for detecting and grading depressive symptoms in Italian MS patients. [ABSTRACT FROM AUTHOR]

Background and purpose: In medication-overuse headache (MOH) patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. This multicentre study aimed to assess the occurrence of psychopathological disorders in MOH patients by comparing the incidence of psychopathological disturbances with episodic migraine (EM) patients and healthy controls (HC). Methods: The psychopathological assessment of patients and HC involved the administrations of the Beck Depression Inventory, the Beck Anxiety Inventory, the Modified Mini International Neuropsychiatric Interview (MMINI), the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Leeds Dependence Questionnaire. Results: The MOH, EM and HC groups (88, 129 and 102 subjects, respectively) differed significantly from each other for the presence of moderate/severe anxiety, whereas mood disorder and depression were revealed in similar proportions for both MOH and EM patients. By stratifying the M-MINI questionnaire results according to the number of psychiatric disorders, it was found that MOH patients had a more complex profile of psychiatric comorbidity. Furthermore, clinically relevant obsessive compulsive disturbances for abused drugs assessed by Y-BOCS appeared to be more represented in the MOH group, whilst the prevalence of this trait in the EM group was comparable to that of HC (12.5%, 0.8% and 0%, respectively). Conclusions: Our study indicates the multiple presence of psychopathological comorbidities in patients with MOH. In light of this, it is recommended that the assessment of the psychopathological profile be included in an evaluation of MOH patients, allowing the clinician to more rapidly start an appropriate behavioural treatment, which would greatly improve MOH management. [ABSTRACT FROM AUTHOR]

Background and purpose: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti-apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS). Methods: As a proof of principle, using a double-blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead-in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope during the treatment period compared to the lead-in phase]. Secondary outcomes included between-treatment comparison of ALSFRS-R at study end, comparison of the linear regression slopes for ALSFFRS-R mean scores and the occurrence of adverse events. Results: Tauroursodeoxycholic acid was well tolerated; there were no betweengroup differences for adverse events. The proportion of responders was higher under TUDCA (87%) than under placebo (P = 0.021; 43%). At study end baseline- adjusted ALSFRS-R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01). Conclusions: This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS. [ABSTRACT FROM AUTHOR]

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing. [ABSTRACT FROM AUTHOR]

Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter volume and white matter volume were estimated using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus ( p < 0.001). Compared to CP, CI RRMS patients showed higher T2-LL ( p = 0.02) and WM atrophy ( p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status. [ABSTRACT FROM AUTHOR]

MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine–threonine kinase that phosphorylates microtubule-associated proteins taking part in the regulation of microtubule dynamics. MARK4 is expressed in two spliced isoforms characterized by inclusion (MARK4S) or exclusion (MARK4L) of exon 16. The distinct expression profiles in the central nervous system and their imbalance in gliomas point to roles of MARK4L and MARK4S in cell proliferation and cell differentiation, respectively. Having ruled out mutations and transcription defects, we hypothesized that alterations in the expression of splicing factors may underlie deregulated MARK4 expression in gliomas. Bioinformatic analysis revealed four putative polypyrimidine-tract binding (PTB) protein binding sites in MARK4 introns 15 and 16. Glioma tissues and glioblastoma-derived cancer stem cells showed, compared with normal brain, significant overexpression of PTB, correlated with high MARK4L mRNA expression. Splicing minigene assays revealed a functional intronic splicing silencer in MARK4 intron 15, but mutagenesis of the PTB binding site in this region did not affect minigene splicing, suggesting that PTB may bind to a splicing silencer other than the predicted one and synergistically acting with the other predicted PTB sites. Electrophoretic mobility shift assays coupled with mass spectrometry confirmed binding of PTB to the polypyrimidine tract of intron 15, and thus its involvement in MARK4 alternative splicing. This finding, along with evidence of PTB overexpression in gliomas and glioblastoma-derived cancer stem cells and differentiated progeny, merged in pointing out the involvement of PTB in the switch to MARK4L, consistent with its established role in driving oncogenic splicing in brain tumors. [ABSTRACT FROM AUTHOR]

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT ( p < 0.01), PASAT 3″ ( p < 0.00), PASAT 2″ ( p < 0.03), SRT-D ( p < 0.02), and 10/36 SPART-D ( p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve. [ABSTRACT FROM AUTHOR]

Post-traumatic headache (PTH) is the most common secondary headache disorder, corresponding to approximately 4 % of all symptomatic headaches. PTH, a cardinal feature of the post-concussive syndrome, usually shows a phenotype similar to migraine or tension-type headache. However, rare cases of PTH similar to trigeminal autonomic cephalalgias have been described. Many studies have investigated PTH prevalence and potential risk factors for its development and maintenance. In general population, the majority of PTH patients is female and has been involved in vehicle-related accidents. Generally, headache gradually disappears over few weeks or months; however, PTH could become persistent and very disabling in a minority of patients. This brief review will focus on PTH epidemiological aspects. [ABSTRACT FROM AUTHOR]

Headache attributed to head and/or neck trauma or injury, the so-called post-traumatic headache (PTH), is the most common secondary headache disorder and one of the most controversial clinical entities in the headache field, due to its unclear pathophysiological mechanisms and the unsolved role of associated psychological and medico-legal aspects. PTH, as a significant cause of morbidity after traumatic brain injury, may occur as an isolated symptom or as one of a constellation of symptoms known as post-concussive syndrome. However, in many cases, PTH might also represent an accentuation of non-disabling, remote or infrequent pre-existing primary headaches rather than a new onset headache strictly related to the trauma. Recently, the International Classification of Headache Disorders attempted to classify PTH; however, many unsolved issues are still to be clarified. In this brief review, we will focus on PTH clinical aspects and diagnostic criteria. [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of longtermclinical progression in a large cohort of multiple sclerosis (MS) patients.Methods: A total of 241 relapsing–remitting (RR) MS patients were included in a nine-year follow-up (FU) study. Thereference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. VolumetricMRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinicalprogression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progressionof Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4.Results: We concluded that conversion from RR to SP (OR 0.79; CI 0.7–0.9), progression of EDSS (OR 0.85; CI 0.77–0.93), achievement of EDSS 4 (OR 0.8; CI 0.7–0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82–0.94) were all predictedby BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9–4.36),(OR 2.7; CI 1.7–4.2), (HR 3.86; CI 1.94–7.70)).Conclusions: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients witha relatively long and mild disease. [ABSTRACT FROM AUTHOR]

Natalizumab is one option for multiple sclerosis patients responding poorly to classical immunomodulators, but pilot studies did not point to its effectiveness as a second-line therapy. Aim of this study was to assess the efficacy of natalizumab as second-line therapy in patients switching from disease modifying therapies (DMTs) in a clinical setting. We retrospectively selected patients who had been treated with natalizumab for at least 12 months after switching from one or more DMTs. We collected clinical and neuroradiological data and we analysed the reduction in annualised relapse rate (ARR), the change of Expanded Disability Status Scale (EDSS) and the reduction of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI) of the brain at 12 months of natalizumab and of previous DMT therapy. Fifty patients were included in the analysis (11 males, 39 females).We observed a reduction of ARR on natalizumab ( p = 0.000) and a statistically significant different trend of relapse event between the two treatments ( p = 0.0149). EDSS was stable during natalizumab therapy whilst it showed an increase on DMTs ( p = 0.0244). The number of CELs decreased significantly ( p = 0.006) during the 12 months of treatment with natalizumab, whilst it was stable on DMTs. Natalizumab showed to decrease ARR, stabilize EDSS, increase the percentage of CELs free patients and decrease the number of CELs in a group of 50 poor responders to classical DMT, after the first 12 months of therapy. [ABSTRACT FROM AUTHOR]

Background - No head-to-head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS). Aim - To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 μg; Rebif®) on clinical and radiological findings in two matched cohorts of patients with MS. Patients and methods - We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing-remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI). Results - In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab-treated group, P < 0.0000; 0.55 vs 1.10 in IFN beta 1a-treated group, P = 0.0006), being the effect of natalizumab significantly stronger ( P = 0.0125). EDSS reduction was significantly different between the two groups in favor of natalizumab ( P = 0.0018). The frequency and number of CELs per patient were decreased in both groups. In the second year, the treatment affected ARR and EDSS progression in the two groups of patients similarly to the first year, whereas number of CELs decreased more significantly in natalizumab group ( P = 0.008). Conclusions - After 12 and 24 months of therapy, natalizumab was more effective than IFN beta 1a SC on both disease activity and disability progression. Prospective head-to-head studies would be helpful to further evaluate the differences observed in the MRI outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Aerosol particles in coastal areas result from a complex mixing between sea-spray aerosols locally generated at the sea surface by breaking waves and a continental component arising from natural and/or anthropogenic sources. This paper presents physicochemical characterization of aerosols observed during meteorological conditions characteristics of coastal areas. In particular, we study the influence of sea-breezes and land-breezes as well as the fetch variation, which superpose on larger synoptic conditions, on aerosol properties. This was achieved using a physical, chemical and optical analysis of the aerosol data acquired in May 2007 on the French Mediterranean coast. The aerosol distributions were measured using a TSI SMPS 3081 model and the chemical characterization was made using an Ion Chromatography analysis (IC) and a thermo-optical technique. In addition, aerosol optical characteristics were provided by aethalometer (absorption) and nephelometer (scattering) measurements. For low wind speeds, we detect high aerosol number concentrations as well as high and carbonaceous compounds contributions, which are observed even when the aerosol is sampled in pure maritime air masses. These results indicate that air masses are strongly impacted by pollution transported over the Mediterranean. In addition, the combination of low wind speeds and land/sea-breezes lead to the production of new ultrafine particle formation events that seem to take place over the sea before being transported back to the coast. Under higher wind speed conditions, aerosol number and mass concentrations of smaller sizes are significantly lowered due to the dispersion of anthropogenic pollutants. Optical measurements reveal that mean scattering and absorbing coefficients are about 15.2 Mm−1 and 3.6 Mm−1, respectively. Associated mean aerosol single scattering albedo is found to be about 0.87 and 0.94 (at 520 nm) for continental and maritime influences. [Copyright &y& Elsevier]

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy. [ABSTRACT FROM AUTHOR]

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter. [ABSTRACT FROM AUTHOR]

Abstract: In the present work we show that murine ATXN3 (ATXN3Q6) nuclear uptake is promoted by phosphorylation on serine 29, a highly conserved residue inside the Josephin domain. Both casein kinase 2 (CK2) and glycogen synthase kinase 3 (GSK3) are able to carry out phosphorylation on this residue. S29 phosphorylation was initially assessed in vitro on purified ATXN3Q6, and subsequently confirmed in transfected COS-7 cells, by MS analysis. Site-directed mutagenesis of S29 to an alanine was shown to strongly reduce nuclear uptake, in COS-7 transiently transfected cells overexpressing ATXN3Q6, while substitution with phospho-mimic aspartic acid restored the wild-type phenotype. Finally, treatment with CK2 and GSK3 inhibitors prevented S29 phosphorylation and strongly inhibited nuclear uptake, showing that both kinases are involved in ATXN3Q6 subcellular sorting. Although other authors have previously addressed this issue, we show for the first time that ATXN3 is phosphorylated inside the Josephin domain and that S29 phosphorylation is involved in nuclear uptake of ATXN3. [Copyright &y& Elsevier]

Background and purpose: The growth hormone (GH) and insulin-like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH–IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features. Methods: Serum levels of GH, IGF-I, IGF-II, insulin, IGF-binding protein 1 (IGF-BP1), and IGF-binding protein 3 (IGF-BP3) were measured in 25 patients with ALS and 25 age-, gender-, and BMI-matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale – Revised (ALSFRS-R) and upper motor neuron (UMN) score. Results:  GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF-I levels were significantly higher in patients with ALS than in healthy controls (182.9 ± 90.8 vs. 139.4 ± 58.1 ng/ml; P = 0.015). IGF-I levels were higher in patients with ALS with UMN score >10 than those with UMN score <10 (217.8 ± 100.8 vs. 155.5 ± 74.6 ng/ml, P = 0.05). IGF-II levels were significantly lower in patients with ALS than in healthy controls (720.9 ± 215 vs. 1001.9 ± 475.4 ng/ml; P = 0.03). Conclusions: The results demonstrate an impairment of the GH–IGFs system in ALS. The degenerative process in ALS might lead to a compensatory increase in IGF-I in an attempt to provide additional support to motor neurons or degenerating muscle fibers. The decrease in IGF-II levels may also be of pathological significance. [ABSTRACT FROM AUTHOR]