Search

Objective: To estimate, in a cohort of young Portuguese adults, the environmental impact (greenhouse gas (GHG) emissions, land use, energy used, acidification and potential eutrophication) of diet according to adherence to the Mediterranean Diet (MD). Methods: Data from 1554 participants of the Epidemiologic Health Investigation of Teenagers in Porto (EPITeen) were analysed. Food intake and MD adherence were determined using validated questionnaires. The environmental impact was evaluated with the EAT-Lancet Commission tables, and the link between MD adherence and environmental impact was calculated using adjusted multivariate linear regression models. Results: Higher adherence (high vs. low) to the MD was associated with lower environmental impact in terms of land use (7.8 vs. 8.5 m2, p = 0.002), potential acidification (57.8 vs. 62.4 g SO2-eq, p = 0.001) and eutrophication (21.7 vs. 23.5 g PO4-eq, p < 0.001). Energy use decreased only in the calorie-adjusted model (9689.5 vs. 10,265.9 kJ, p < 0.001), and GHG emissions were reduced only in a complementary model where fish consumption was eliminated (3035.3 vs. 3281.2 g CO2-eq, p < 0.001). Meat products had the greatest environmental impact for all five environmental factors analysed: 35.7% in GHG emissions, 60.9% in energy use, 72.8% in land use, 70% in acidification and 61.8% in eutrophication. Conclusions: Higher adherence to the MD is associated with lower environmental impact, particularly in terms of acidification, eutrophication, and land use. Reducing meat consumption can contribute to greater environmental sustainability. [ABSTRACT FROM AUTHOR]

Background: Monoaminergic network dysfunction is thought to underpin depression in multiple sclerosis (MS) patients. However, longitudinal studies are lacking. Objectives: Here, we investigated the association between development of depressive symptoms in MS and changes of resting-state functional connectivity (RS FC) within monoaminergic networks. Methods: Forty-nine MS patients without depression [Montgomery–Asberg Depression Scale (MADRS) ≤ 9] and 27 healthy controls underwent clinical and 3.0 T RS FC assessment at baseline and after a median follow-up of 1.6 years (interquartile range 1.0–2.1 years). Monoamine-related RS FC was derived by independent component analysis, constrained to PET atlases for dopamine, noradrenaline and serotonin transporters. Longitudinal changes of RS FC within monoaminergic networks and their correlations with MADRS scores were assessed. Results: At baseline, MS patients showed decreased RS FC vs healthy controls in all PET-guided monoaminergic networks in frontal, cingulate and cerebellar cortices, and increased RS FC in parieto-occipital regions. Fourteen (29%) MS patients developed depressive symptoms (MADRS > 9) at follow-up (D-MS) and exhibited widespread RS FC decrease over time in the PET-guided dopamine network, mainly in orbitofrontal, occipital, anterior cingulate and precuneal cortices compared to patients who did not develop depressive symptoms. In D-MS, decreased RS FC over time was also observed in parahippocampal and occipital regions of the PET-guided noradrenaline network. Decreased RS FC over time in dopamine and noradrenaline PET-guided networks correlated with concomitant increased MADRS scores (r = range − 0.65/− 0.61, p < 0.001). Conclusions: The development of depressive symptoms in MS patients was associated with specific RS FC changes within the dopamine and noradrenaline networks. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a common clinical manifestation in people with multiple sclerosis (PwMS) and significantly impacts patients' quality life. Cognitive assessment is crucial for treatment decisions and understanding disease progression. Several neuropsychological batteries are used in MS, including the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Minimal Assessment of Cognitive Function in MS (MACFIMS), and Brief International Cognitive Assessment for MS (BICAMS). However, normative data for BRB-N version A in Italy are outdated. Objectives: To revise and update normative data for the BRB-N version A in the Italian population. Methods: From the Italian Neuroimaging Network Initiative (INNI) database, we retrospectively selected 342 healthy subjects (172 males and 170 females) evaluated at four Italian INNI-affiliated sites (Milan, Siena, Rome, Naples). The subjects underwent neuropsychological assessment using the BRB-N version A. Regression-based method relying on scaled scores was used to calculate demographic correction procedures. Results: No significant differences were found in age, education, and sex distribution among the four sites (p ≥ 0.055). Regression analysis provided normative data to calculate demographically adjusted z-scores for each BRB-N version A test. Discussion: This study provides updated normative data for the BRB-N version A in the Italian population. The use of a regression-based method and scaled scores ensures consistency with other neuropsychological batteries commonly used in Italy, namely MACFIMS and BICAMS. The availability of updated normative data increases reliability of neuropsychological assessment of cognitive function in Italian PwMS and other clinical populations using BRB-N version A, providing valuable insights for both clinical and research applications. [ABSTRACT FROM AUTHOR]

Background: Impairment of cardiovascular control is common in multiple sclerosis (MS), possibly due to damage of strategic brain regions such as the insula. Aerobic training (AT) targets cardiopulmonary system and may represent a neuroprotective strategy. Purpose: To investigate whether insular damage (T2-hyperintense lesions and volume) is associated with cardiovascular fitness (CF) and influences AT effects in MS. Methods: Sixty-one MS patients were randomized to an AT intervention group (MS-AT) and a motor training control group (MS-C). At baseline and after training (24 sessions over 2–3 months), peak of oxygen consumption (VO2max), heart rate reserve (HRR), 6-min walk test (6MWT) and whole brain and insula MRI data were collected. Two healthy control (HC) groups were enrolled for CF and MRI data analysis. Results: At baseline, MS patients vs HC showed impaired VO2max, HRR and 6MWT (p < 0.001) and widespread gray matter atrophy, including bilateral insula. In MS patients, left insula T2-lesion volume correlated with HRR (r = 0.27, p = 0.042). After training, MS-AT, especially those without insular T2-hyperintense lesions, showed 6MWT improvement (p < 0.05) and a stable insular volume, whereas MS-C showed left insular volume loss (p < 0.001). Conclusions: By increasing 6MWT performance, our results suggest that AT may improve walking capacity and submaximal measure of CF in MS patients. Such beneficial effect may be modulated by insula integrity. [ABSTRACT FROM AUTHOR]

The Italian Neuroimaging Network Initiative (INNI) is an expanding repository of brain MRI data from multiple sclerosis (MS) patients recruited at four Italian MRI research sites. We describe the raw data quality of resting-state functional MRI (RS-fMRI) time-series in INNI and the inter-site variability in functional connectivity (FC) features after unified automated data preprocessing. MRI datasets from 489 MS patients and 246 healthy control (HC) subjects were retrieved from the INNI database. Raw data quality metrics included temporal signal-to-noise ratio (tSNR), spatial smoothness (FWHM), framewise displacement (FD), and differential variation in signals (DVARS). Automated preprocessing integrated white-matter lesion segmentation (SAMSEG) into a standard fMRI pipeline (fMRIPrep). FC features were calculated on pre-processed data and harmonized between sites (Combat) prior to assessing general MS-related alterations. Across centers (both groups), median tSNR and FWHM ranged from 47 to 84 and from 2.0 to 2.5, and median FD and DVARS ranged from 0.08 to 0.24 and from 1.06 to 1.22. After preprocessing, only global FC-related features were significantly correlated with FD or DVARS. Across large-scale networks, age/sex/FD-adjusted and harmonized FC features exhibited both inter-site and site-specific inter-group effects. Significant general reductions were obtained for somatomotor and limbic networks in MS patients (vs. HC). The implemented procedures provide technical information on raw data quality and outcome of fully automated preprocessing that might serve as reference in future RS-fMRI studies within INNI. The unified pipeline introduced little bias across sites and appears suitable for multisite FC analyses on harmonized network estimates. [ABSTRACT FROM AUTHOR]

Background: In multiple sclerosis (MS), determination of regional brain atrophy is clinically relevant. However, analysis of large datasets is rare because of the increased variability in multicenter data. Purpose: To compare different methods to correct for center effects. To investigate regional gray matter (GM) volume in relapsing–remitting MS in a large multicenter dataset. Methods: MRI scans of 466 MS patients and 279 healthy controls (HC) were retrieved from the Italian Neuroimaging Network Initiative repository. Voxel-based morphometry was performed. The center effect was accounted for with different methods: (a) no correction, (b) factor in the statistical model, (c) ComBat method and (d) subsampling procedure to match single-center distributions. By applying the best correction method, GM atrophy was assessed in MS patients vs HC and according to clinical disability, disease duration and T2 lesion volume. Results were assessed voxel-wise using general linear model. Results: The average residuals for the harmonization methods were 5.03 (a), 4.42 (b), 4.26 (c) and 2.98 (d). The comparison between MS patients and HC identified thalami and other deep GM nuclei, the cerebellum and several cortical regions. At single-center analysis, the thalami were always involved, whereas different other regions were found in each center. Cerebellar atrophy correlated with clinical disability, while deep GM nuclei atrophy correlated with T2-lesion volume. Conclusion: Harmonization based on subsampling more effectively decreased the residuals of the statistical model applied. In comparison with findings from single-center analysis, the multicenter results were more robust, highlighting the importance of data repositories from multiple centers. [ABSTRACT FROM AUTHOR]

This study provides valuable information on the levels of various trace metals (Pb, Cd, Hg, Zn, Cu, Cr) in meat products (baked ham, raw ham, mortadella, cured sausage, würstel, salami) from South Italy and calculates potential health risk toxicity associated with their consumption for the total population and for children. In the samples studied metal concentrations are within the permissible legal limits (Cd: 0.01–0.03 μg g−1 w.w., Hg: 0.01–0.02 μg g−1 w.w., Zn: 5.71–7.32 μg g−1 w.w., Cu: 1.08–1.21 μg g−1 w.w., Cr: 0.15–0.23 μg g−1 w.w.), except for Pb (Pb: 0.22–0.38 μg g−1 w.w.). The estimated intake values are within the provisional tolerable daily intake limits for toxic metals and recommended daily intake values for essential metals in both tested groups. The noncarcinogenic risk values of the individual metals indicate that there is no health risk, but their combined effects might constitute a potential risk for children. Furthermore, the cumulative cancer risk of all samples studied exceeds the recommended threshold risk limit (> 10−4) in both total population and children, indicating a risk of potential health problems for consumers especially for children, who are more vulnerable to toxic metal exposure. [ABSTRACT FROM AUTHOR]

Background: White matter (WM) atrophy is relevant in multiple sclerosis (MS), but the methods of analysis currently used are not specific for microstructural changes. The aims of this study were to assess the use of advanced diffusion-weighted imaging (DWI) techniques proposed as measures of baseline and longitudinal WM atrophy in MS and to analyze whether these measures helped explain MS clinical disability (including cognitive impairment) better than volumetric and diffusion tensor (DT)-derived measures. Methods: 3DT1-weighted and DWI sequences were applied to 86 MS and 55 healthy controls (HC) at baseline and after one-year. Intra-cellular volume (vic) maps were computed from neurite orientation dispersion and density imaging model. Voxel-wise fiber-bundle cross-section (FCS) atrophy in MS compared to HC was estimated. Maps of fractional anisotropy and mean diffusivity were also obtained from DWI for a comparison with the proposed advanced DW-derived measures (vic and FCS). Results: Both at baseline and after 1-year, only FCS measure showed a significant atrophy in relapsing–remitting (RR) MS compared to HC and in progressive MS compared to RRMS, mainly located in specific WM tracts (corticospinal tract, splenium of the corpus callosum, left optic radiation, bilateral cingulum, middle cerebellar peduncle and anterior commissure, p value < 0.05). Global baseline FCS and vic were the selected predictors of clinical (R-sq = 0.33, p = 0.007) and cognitive scores (R-sq = 0.29, p = 0.0014) in a linear regression model. Conclusion: Voxel-based FCS was able to detect WM tracts atrophy in MS clinical phenotypes with greater anatomical specificity compared to other measures (volumetric and DT-derived measures of WM damage). FCS and vic measured at baseline in the WM were the best predictors of clinical disability and cognitive impairment. [ABSTRACT FROM AUTHOR]

The aim of this work was to prepare silk fibroin (SF) membranes incorporated with cationic and anionic dyes, in order to analyze the behavior of SF matrix loaded with charged compounds. For that, the combinatorial effect of pH and ionic strength on the release kinetics was assessed, showing that cationic dye has poor interaction with SF and high release rate, whereas anionic dye presented strong hydrophobic interactions with SF, being retained within the matrix. These results help elucidate the behavior of SF in the presence of charged dyes, which can be outspread for the release of charged drugs. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated an association between motor and cognitive performance in multiple sclerosis (MS). However, disease-related brain damage might represent a common substrate to both phenomena, which was not considered before. Objective: Aim of this study is to investigate whether the association between cognition and motor function is beyond structural damage in patients with MS. Methods: Eighty-one healthy controls and 106 relapsing–remitting (RR) MS patients underwent a 3.0 T MRI with quantification of T2-lesion volumes, T1-lesion volumes and normalized brain volumes. A functional examination [Nine-Hole Peg Test (9-HPT), Timed 25-Foot Walk test (T25FW) and Expanded Disability Status Scale] and a neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests) were also administered. Association between demographic, clinical, cognitive, MRI and functional measures were analysed with univariate analyses and hierarchical linear regression. Results: In RRMS patients, Spatial Recall Test and Symbol Digit Modalities Test were positively correlated with 9-HPT (p < 0.001) and T25FW (p ≤ 0.035); Paced Auditory Serial Addition Test (PASAT) correlated with 9-HPT (p ≤ 0.009). 9-HPT and T25FW were significantly associated with normalized brain volumes (p ≤ 0.016), T2- and T1-lesion volumes (p ≤ 0.009). Hierarchical regression models selected age and normalized deep gray matter volume as predictors of T25FW (adjusted-R2 = 0.109). Younger age, female sex, higher normalized gray matter volume and higher PASAT 2″ scores predicted higher 9-HPT scores (adjusted-R2 = 0.337). Conclusions: In RRMS patients, deficit in information processing speed and executive function may contribute to hand motor dysfunction beyond the effect of structural disease-related burden, supporting the integration of motor and cognitive assessment in clinical settings. [ABSTRACT FROM AUTHOR]

Objectives: To apply a deep-learning algorithm to brain MRIs of seronegative patients with neuromyelitis optica spectrum disorders (NMOSD) and NMOSD-like manifestations and assess whether their structural features are similar to aquaporin-4-seropositive NMOSD or multiple sclerosis (MS) patients. Patients and methods: We analyzed 228 T2- and T1-weighted brain MRIs acquired from aquaporin-4-seropositive NMOSD (n = 85), MS (n = 95), aquaporin-4-seronegative NMOSD [n = 11, three with anti-myelin oligodendrocyte glycoprotein antibodies (MOG)], and aquaporin-4-seronegative patients with NMOSD-like manifestations (idiopathic recurrent optic neuritis and myelitis, n = 37), who were recruited from February 2010 to December 2019. Seventy-three percent of aquaporin-4-seronegative patients with NMOSD-like manifestations also had a clinical follow-up (median duration of 4 years). The deep-learning neural network architecture was based on four 3D convolutional layers. It was trained and validated on MRI scans of aquaporin-4-seropositive NMOSD and MS patients and was then applied to aquaporin-4-seronegative NMOSD and NMOSD-like manifestations. Assignment of unclassified aquaporin-4-seronegative patients was compared with their clinical follow-up. Results: The final algorithm differentiated aquaporin-4-seropositive NMOSD and MS patients with an accuracy of 0.95. All aquaporin-4-seronegative NMOSD and 36/37 aquaporin-4-seronegative patients with NMOSD-like manifestations were classified as NMOSD. Anti-MOG patients had a similar probability of being NMOSD or MS. At clinical follow-up, one unclassified aquaporin-4-seronegative patient evolved to MS, three developed NMOSD, and the others did not change phenotype. Conclusions: Our findings support the inclusion of aquaporin4-seronegative patients into NMOSD and suggest a possible expansion to aquaporin-4-seronegative unclassified patients with NMOSD-like manifestations. Anti-MOG patients are likely to have intermediate brain features between NMOSD and MS. [ABSTRACT FROM AUTHOR]

Ditylenchus dipsaci is an economically important plant-parasitic nematode affecting European sugar beets. To date, no sugar beet cultivars carrying resistance against D. dipsaci are available to farmers. To find potentially resistant sugar beet lines restricting reproduction and penetration of D. dipsaci, three consecutive in vivo bioassays were carried out. The first experiment determined the penetration rate of D. dipsaci in 79 breeding lines and 14 pre-breeding populations. Based on these results, D. dipsaci penetration and reproduction resistance of eight genotypes was intensively investigated. It could be demonstrated that none of the genotypes showed resistance towards D. dipsaci. However, a high variation of the penetration rate by D. dipsaci was observed among the genotypes. The breeding line 'DIT_119' effectively reduced D. dipsaci penetration (34.4 ± 8.8 nematodes/plant at 22 days post-planting) compared to the susceptible control (109.0 ± 16.9) while ensuring a yield comparable to non-inoculated plants. However, the breeding line 'DIT_119' did not reduce D. dipsaci reproduction. The paternal line of the cultivar BERETTA KWS, demonstrating a high tolerance to D. dipsaci crown rot symptoms, did not reduce penetration and reproduction. Thus, no correlation can be established between reduced penetration rates, reproduction, and tolerance to D. dipsaci. This study provides an essential basis for the development of resistant sugar beet cultivars to D. dipsaci. The variations observed among genotypes now need to be confirmed with larger-scale screenings. [ABSTRACT FROM AUTHOR]

The stem nematode, Ditylenchus dipsaci, is a severe pest in European sugar beet production. In France, Germany, and Switzerland, D. dipsaci damage in sugar beet varies among specific geographic areas. In this study, the reproduction potential of four geographically distinct D. dipsaci populations was determined using sterile carrot disc cultures. In addition, virulence and pathogenicity were investigated in-vivo using sugar beet. No difference was found in the reproduction potential on carrot discs, as well as penetration rate in sugar beet seedlings. The reproduction rate in sugar beet tissue was significantly affected by the D. dipsaci population used. The population from Seeland (CH) showed the highest number of nematodes per plant at 60 dpi (21,071.8 ± 5340.0), compared to the three other populations contained 3588.6 ± 3858.3, 5136.9 ± 4950.8, and 3579.7 ± 5174.2, respectively. Furthermore, the reproduction rate of D. dipsaci was negatively correlated with fresh biomass of sugar beets at 60 dpi. Based on these results, the D. dipsaci population "Seeland" is suitable for breeding programs to detect resistance in sugar beet. After selecting candidate genotypes/varieties, these should be further evaluated for their field resistance in their targeted growing regions. [ABSTRACT FROM AUTHOR]

Biological N2 fixation was key to the expansion of life on early Earth. The N2-fixing microorganisms and the nitrogenase type used in the Proterozoic are unknown, although it has been proposed that the canonical molybdenum-nitrogenase was not used due to low molybdenum availability. We investigate N2 fixation in Lake Cadagno, an analogue system to the sulfidic Proterozoic continental margins, using a combination of biogeochemical, molecular and single cell techniques. In Lake Cadagno, purple sulfur bacteria (PSB) are responsible for high N2 fixation rates, to our knowledge providing the first direct evidence for PSB in situ N2 fixation. Surprisingly, no alternative nitrogenases are detectable, and N2 fixation is exclusively catalyzed by molybdenum-nitrogenase. Our results show that molybdenum-nitrogenase is functional at low molybdenum conditions in situ and that in contrast to previous beliefs, PSB may have driven N2 fixation in the Proterozoic ocean. N2 fixation was key to the expansion of life on Earth, but which organisms fixed N2 and if Mo-nitrogenase was functional in the low Mo early ocean is unknown. Here, the authors show that purple sulfur bacteria fix N2 using Mo-nitrogenase in a Proterozoic ocean analogue, despite low Mo conditions. [ABSTRACT FROM AUTHOR]

Research misconduct (RM) is an alarming concern worldwide, and especially in Italy, where there is no formal training of young researchers in responsible research practices. The main aim of this study was to map the perceptions and attitudes about RM in a sample of young researchers attending a one-week intensive course on methodology, ethics and integrity in biomedical research, held at the University of Insubria (Italy). To this end, we administered the Scientific Misconduct Questionnaire (SMQ-R) to all attendees at the beginning of the course. Thereafter, SMQ-R was re-administered at the end, to assess the impact of the course on the responsiveness of study participants, which is intended as the frequency of responses other than "don't know". Results show that respondents rate as high their own understanding about rules and procedures related to scientific misconduct (49.2% of respondents), as well as the effectiveness of their institution's measures for reducing it (40%). Most of them (44.6%) perceive as low the chances of getting caught for RM. Some respondents believe that cases of misconduct occur in their workplace (20%–46.2%) and that the integrity of a research is not solely the responsibility of the principal investigator (73.8%). Among the main factors contributing to research misconduct, the need for publications, unclear definition of what constitutes misconduct and pressure for external funding do stand out. Respondents are concerned about the amount of misconduct and express a pressing need for training on research ethics. Remarkably, the responsiveness of participants tends to increase with course attendance. This finding may be useful to support education programmes devoted to research methodology, ethics and integrity among young researchers. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine and compare the concentrations of Hg, Cd, Pb, Zn, Cu, Ni and Se in the liver of macrourid fish as Trachyrinchus scabrus, Nezumia sclerorhynchus and Coelorhynchus coelorhynchus from the Mediterranean Sea, Italy. It was also carried out to evaluate the relationship between metal concentration and fish size and to explore selenium/mercury molar ratio. The highest concentrations were in T. scabrus, followed by N. sclerorhynchus and C. coelorhynchus. In all species, any element displayed significant correlation between metal body burden and fish size, except Hg. The mean selenium/mercury ratios were greater than one in all fish species indicating that Se antidotal effect in counteracting Hg occurred. This report represents one of the few surveys providing information on trace metal in deep-sea fish from Mediterranean Sea constituting, thus, an essential baseline work with which future levels may be compared. [ABSTRACT FROM AUTHOR]

The Italian Neuroimaging Network Initiative (INNI) supports the creation of a repository, where MRI, clinical, and neuropsychological data from multiple sclerosis (MS) patients and healthy controls are collected from Italian Research Centers with internationally recognized expertise in MRI applied to MS. However, multicenter MRI data integration needs standardization and quality control (QC). This study aimed to implement quantitative measures for characterizing the standardization and quality of MRI collected within INNI. MRI scans of 423 MS patients, including 3D T1- and T2-weighted, were obtained from INNI repository (from Centers A, B, C, and D). QC measures were implemented to characterize: (1) head positioning relative to the magnet isocenter; (2) intensity inhomogeneity; (3) relative image contrast between brain tissues; and (4) image artefacts. Centers A and D showed the most accurate subject positioning within the MR scanner (median z-offsets = − 2.6 ± 1.7 cm and − 1.1 ± 2 cm). A low, but significantly different, intensity inhomogeneity on 3D T1-weighted MRI was found between all centers (p < 0.05), except for Centers A and C that showed comparable image bias fields. Center D showed the highest relative contrast between gray and normal appearing white matter (NAWM) on 3D T1-weighed MRI (0.63 ± 0.04), while Center B showed the highest relative contrast between NAWM and MS lesions on FLAIR (0.21 ± 0.06). Image artefacts were mainly due to brain movement (60%) and ghosting (35%). The implemented QC procedure ensured systematic data quality assessment within INNI, thus making available a huge amount of high-quality MRI to better investigate pathophysiological substrates and validate novel MRI biomarkers in MS. [ABSTRACT FROM AUTHOR]

Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug-drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs. This variability results in poor predictability of DDIs and potentially dramatic clinical consequences. The present review illustrates the issue of complex DDIs using systematically searched published case reports of DDIs involving genetic polymorphisms, renal impairment, cirrhosis, and/or inflammation. Current knowledge on the impact of each of these factors on drug exposure and DDIs is summarized and future perspectives for the management of such complex DDIs in clinical practice are discussed, including the use of advanced Computerized Physician Order Entry (CPOE) systems, the development of model-based dose optimization strategies, and the education of healthcare professionals with respect to personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Treatment choice in multiple sclerosis (MS) is crucial for optimizing risk-benefit profile.Objective: To assess fingolimod (FTY) effectiveness and identify baseline features associated to disease activity in a large Italian cohort of Relapsing-Remitting (RR) MS patients.Methods: Three-hundred sixty-seven RRMS patients starting FTY treatment at San Raffaele Hospital (Milan-Italy) underwent clinical and MRI evaluations for 2 years. Treatment response was assessed considering the proportion of patients with no evidence of disease activity (NEDA) and recording the time to first relapse. Primary analyses were performed stratifying for Natalizumab (NTZ) treatment in the year before (NO_NTZ vs NTZ group), to account for post-NTZ reactivation.Results: Almost half of patients were NEDA after 2 years, 53.4% in the NO_NTZ group and 36.2% in the NTZ group. Despite an opposite trend during the first 6-12 months, at 2-year follow-up the two groups were comparable for relapses and number of new/enlarging T2 and Gd-enhancing lesions. Baseline parameters of higher disease activity (ARR, Gd enhancing lesions and age at onset) were associated with increased likelihood of failing NEDA criteria or with shorter time to relapse (p < 0.05).Conclusions: Our data strengthen FTY effectiveness in everyday clinical practice, even in patients switching from NTZ treatment. Baseline parameters of inflammatory activity are the most important prognostic factors for mid-term disease reactivation also during second-line treatment with FTY, providing hints on how to select therapies towards a more personalized management. [ABSTRACT FROM AUTHOR]

Solute Carrier 15 (SLC15) family, alias H-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their role in the cellular uptake of di- and tripeptides (di/tripeptides) and peptide-like molecules. Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, while SLC15A2 (PEPT2) mainly allows renal tubular reabsorption of di/tripeptides from ultrafiltration, SLC15A3 (PHT2) and SLC15A4 (PHT1) possibly interact with di/tripeptides and histidine in certain immune cells, and SLC15A5 has unknown function. Our understanding of this family in vertebrates has steadily increased, also due to the surge of genomic-to-functional information from 'non-conventional' animal models, livestock, poultry, and aquaculture fish species. Here, we review the literature on the SLC15 transporters in teleost fish with emphasis on SLC15A1 (PEPT1), one of the solute carriers better studied amongst teleost fish because of its relevance in animal nutrition. We report on the operativity of the transporter, the molecular diversity, and multiplicity of structural-functional solutions of the teleost fish orthologs with respect to higher vertebrates, its relevance at the intersection of the alimentary and osmoregulative functions of the gut, its response under various physiological states and dietary solicitations, and its possible involvement in examples of total body plasticity, such as growth and compensatory growth. By a comparative approach, we also review the few studies in teleost fish on SLC15A2 (PEPT2), SLC15A4 (PHT1), and SLC15A3 (PHT2). By representing the contribution of teleost fish to the knowledge of the physiology of di/tripeptide transport and transporters, we aim to fill the gap between higher and lower vertebrates. [ABSTRACT FROM AUTHOR]

This article discusses the levels of polychlorinated biphenyls (PCBs) in Mediterranean bottlenose dolphins. The distribution of PCBs in dolphin livers, kidneys and muscle tissue was determined. The authors calculate the toxic equivalent concentrations (TEQs) based on available toxic equivalent factors of a number of congeners along with their relative contribution to the total toxic burden in the analyzed tissues. They conclude that the total levels of PCBs are high and distributed homogeneously throughout the tissues studied. Also, the dioxin-like toxic equivalents were high, but non-ortho coplanar congeners were influenced by tissue type.

No abstract available. [ABSTRACT FROM AUTHOR]

This article focuses on polychiorinated biphenyls. The group of polychlorinated biphenyls (PCBs) comprise 209 synthetic compounds, reflecting a different chlorination with respect to the number and the position on the two coupled biphenyl rings. Several studies have shown that these compounds exhibit a broad range of toxicological responses including immunotoxicity, reproductive deficits, teratogenicity, endocrine toxicity and carcinogenity/tumor promotion. The determination of polychiorinated biphenyls in fish species representative of different regions may provide relevant information on pollution sources, transport pathways, spatial distributions and fate in the marine environment.

Purpose: The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action. Methods: Human endothelial cells were incubated with increasing concentrations (1-50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1-25 μmol/L), including hydroxycinnamic acids ( p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes ( trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial-monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1. Results: Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress. Conclusions: This study showed multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including atherosclerosis. [ABSTRACT FROM AUTHOR]

This study provides, for the first time, data regarding levels of toxic metals (Hg, Cd, and Pb) and organochlorine compounds (PCBs and DDTs) in various aromatic herbs as rosemary ( Rosmarinus officinalis), sage ( Salvia officinalis), laurel ( Laurus nobilis), oregano ( Origanum vulgare), and spearmint ( Mentha viridis) collected in some towns of the Southern Italy with different anthropogenic and population pressure. Metal and organochlorine compound concentrations were determined using atomic absorption spectrophotometer and gas-chromatography mass spectrometer (GC/MS), respectively. Pb emerged as the most abundant element, followed by Cd and Hg, while between organochlorine compounds, PCB concentrations were higher than those of DDTs. The pollutant concentrations were found to vary depending on the different herbs. The highest Pb levels were observed in rosemary (1.66 μg g dry weight) and sage (1.41 μg g dry weight), this latter showing also the highest Cd concentrations (0.75 μg g dry weight). For PCBs, the major concentrations were found in rosemary (2.75 ng g dry weight) and oregano (2.39 ng g dry weight). The principal component analysis applied in order to evaluate possible similarities and/or differences in the contamination levels among sampling sites indicated differences area-specific contamination. [ABSTRACT FROM AUTHOR]

Concentrations of polychlorinated biphenyls (PCBs) including dioxin-like PCBs (non- ortho, PCB 77, PCB 126, and PCB 169 and mono- ortho, PCB 105, PCB 118, and PCB 156) were measured in different organs and tissues (melon, blubber, liver, kidney, lung, heart, and muscle tissue) of striped dolphins ( Stenella coeruleoalba) from the Eastern Mediterranean Sea (Adriatic Sea). The mean highest levels were in blubber and melon, followed by liver, kidney, lung, heart, and muscle tissue. PCB profiles were similar in all tissues and organs being dominated by the higher chlorinated homologues (hexa-CBs, 55.8-62.1%; penta-CBs, 15.4-20.0%; and hepta-CB PCB 180, 12.7-16.5%). Major PCBs in all tissues were congeners 138 and 153 collectively accounting for 50.6-58.3% of the total PCB concentrations, followed by PCB 101, 105, 118, and 180 constituting from 27.0% to 31.0%. PCB levels were higher in adult males than in adult females. The estimated 2,3,7,8-TCDD toxic equivalents of non- and mono- ortho PCBs were much higher than the threshold level above which adverse effects have been observed in other marine mammals species, suggesting that striped dolphins in this region are at risk for toxic effects. [ABSTRACT FROM AUTHOR]

The present study provides novel data regarding levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (DDTs) in muscle tissue of European conger eel ( Conger conger) from Ionian Sea (Mediterranean Sea). The mean concentration of PCBs (891 ng g lipid weight) was higher than those of DDTs (543 ng g lipid weight). PCB pattern was dominated by higher chlorinated congeners (hexa-CBs: 69.3 %, penta-CBs: 17.2 %, hepta-CBs: 13.3 %). Regarding DDT pattern, p,p′-DDE was prevalent in all samples (85.5 %), suggesting no recent DDT input. The total 2,3,7,8-TCDD toxic equivalent (TEQs) of coplanar PCBs, including mono-and non- ortho congeners was 0.41 pg g wet weight (29.92 pg g lipid weight). The PCB and DDT levels, as well as TEQ concentrations were lower than most of the corresponding published data for fish from Mediterranean and non-Mediterranean regions, probably reflecting a moderately contaminated area. [ABSTRACT FROM AUTHOR]

Purpose: Polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and PCB congeners accumulation profile were measured in the liver of two torpedinid species ( Torpedo nobiliana and Torpedo marmorata) from the Mediterranean Sea (Adriatic Sea) in order to investigate the relative toxicological impact of these highly toxic PCBs in the organisms in question. Methods: A Thermo Trace GC connected to a Thermo PolarisQ MS operated in electron impact ionization (EI) mode was used to quantify PCBs and DDTs. The method performance was assessed through participation in interlaboratory studies organized by QUASIMEME. Results: PCBs emerged as the most abundant pollutants, followed by DDTs. Contaminant load was higher in T. nobiliana (PCBs, 1,040 ng g lipid weight; DDTs, 234 ng g lipid weight) than in T. marmorata (PCBs, 434 ng g lipid weight; DDTs, 78 ng g lipid weight). PCB 118, 138, 153, and 180 were the dominant congeners accounting for over 95.0% of the total PCBs. Among DDTs, p,p'-DDE was detected in both species, always with a greater concentration than other pesticides. Conclusions: This study provides, for the first time, data regarding levels of organochlorine contamination in torpedinid species from the Mediterranean Sea. The comparability of TEQ levels with those encountered in predators at top of trophic chains constitutes a warning signal that should not be underestimated. [ABSTRACT FROM AUTHOR]

Aberrant methylation of CpG islands in the promoter regions of tumour cells results in loss of gene function. In addition to genetic lesions, changes in the methylation profile of the promoters may be considered a factor for tumour-specific aberrant expression of the genes.We investigated the methylation status of E-cadherin gene ( CDH1) promoter in low-grade glioma and correlated it with clinical outcome. Eighty-four cases of low-grade glioma (43 diffuse astrocytomas, 27 oligodendrogliomas and 14 oligoastrocytomas) with assessable paraffin-embedded tumour blocks and normal brain tissue, derived from non-cancerous tissue adjacent to tumour and commercially normal brain tissue, were collected, from which we determined CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry, respectively. CDH1 promoter was found hypermethylated in 54 out of 84 low grade gliomas (64%) compared with 84 normal brain tissue. CDH1 hypermethylation was found in 65% astrocytomas, 66% oligodendrogliomas and 57% oligoastrocytomas. A significant correlation between hypermethylation status, patient survival and progression-free survival was found ( P = 0.04). Survival and progression-free survival were lower in patients with hypermethylated CDH1 promoter. We found that 15 astrocytomas, 9 oligodendrogliomas and 6 oligoastrocytomas were immunoreactive for E-cadherin. The incidence of loss of immunoreactivity for E-cadherin decreased significantly with age, overall survival and progression-free survival ( P = 0 .001, Kaplan-Meier test). We have demonstrated that CDH1 promoter hypermethylation significantly associated with down-regulated E-cadherin expression and overall survival of patients. This may have a bearing on the prognosis of low-grade glioma. [ABSTRACT FROM AUTHOR]

Trace element concentrations (Hg, Cd, Pb, Cr, Ni, Cu, Zn) were determined in the muscle, gonads, skin, and brain of smooth hound Mustelus mustelus in order to define the metal distribution patterns. The data indicated that metal accumulation depended on the tissues probably as a consequence of metabolic needs, physiochemical properties, and detoxification processes specific for each element. Metal concentrations were higher in gonads (Hg 0.10-0.70 μg g; Cd 0.02-0.10 μg g; Pb 0.08-0.39 μg g; Cr 0.06-0.36 μg g; Ni 1.37-3.00 μg g; Zn 9.15-16.30 μg g; Cu 1.95-21.62 μg g) and skin (Hg 0.16-0.66 μg g; Cd 0.01-0.04 μg g; Pb 0.10-0.62 μg g; Cr 0.15-0.68 μg g; Ni 1.60-7.20 μg g; Zn 9.00-16.00 μg g; Cu 0.78-6.80 μg g) than brain (Hg 0.04-0.34 μg g; Cd 0.01-0.05 μg g; Pb 0.03-0.59 μg g; Cr 0.08-0.48 μg g; Ni 5.59-9.69 μg g; Zn 5.90-7.35 μg g; Cu 0.90-4.02 μg g), while muscle always exhibited the lowest levels (Hg 1.03-2.58 μg g; Cd 0.01-0.06 μg g; Pb 0.02-0.16 μg g; Cr 0.05-0.28 μg g; Ni 1.13-2.48 μg g; Zn 2.64-5.06 μg g; Cu 0.33-2.23 μg g). Ni and Hg took exception having the highest concentrations in brain and muscle, respectively. An assessment of the risk for human due to the consumption of these marine organisms was also undertaken. Regarding Cd and Pb intakes, consumption did not guide to any concerns, while it should be extremely moderate when considering Hg intake. The comparative analyses revealed that Mediterranean sharks were exposed to higher Hg levels than biota inhabiting open ocean. [ABSTRACT FROM AUTHOR]

Background, aim and scope Polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT) concentrations were determined in the liver of two deep sea fish species, Mediterranean slimehead and blackfin sorcerer, from the Adriatic Sea (southeastern Mediterranean Sea). Results and discussion The examination of congener profiles showed that hexachlorinated molecules were dominant (hexa- CBs, 55.3-56.2%), followed by penta-CBs (21.5-21.8%) and hepta-PCB 180 (14.9-16.0%). PCB 138, 153 and 180 were the prominent congeners accounting for 69.3% of the total PCBs. Among the compounds of DDT, p,p'-DDE was the most dominant molecule (Mediterranean slimehead, 86.6%; blackfin sorcerer, 92.8%), demonstrating the old age of these compounds in the environment. In both species, PCB contents were higher than those of DDTs. Contaminant load was higher in Mediterranean slimehead (PCBs, 1,086 ng g-1 lipid weight; DDTs, 799 ng g-1 lipid weight) than in blackfin sorcerer (PCBs, 561 ng g-1 lipid weight; DDTs, 224 ng g-1 lipid weight). Conclusion The high ratios SPCBs/SDDTs indicated predominantly industrial versus agrarian activities in the area. Dioxins toxic equivalent (TEQ) concentrations (8.1-18.7 pg TEQ per gram wet weight) reached those encountered in marine organisms at higher levels in the trophic chain, revealing the onerous status of contamination by PCBs in Mediterranean deep sea biota. [ABSTRACT FROM AUTHOR]

Abstract  We developed an array-based subtractive hybridization system for one-step high-throughput subtraction. We printed subtractor RNA up to 10.000 times obtaining an excellent contact surface using a little amount of RNA. During hybridization cDNA, common to subtractor and target samples, remains attached to slide immobilized RNA, leaving free in solution target specific cDNA which after retrieval is cloned. [ABSTRACT FROM AUTHOR]

Dysregulated body copper homeostasis can negatively impact neuronal functions, but full knowledge of the mechanisms underlying the cell metal distribution has not been achieved yet. The high-affinity copper transporter 1 (Ctr1) is considered the main route for cell copper entry, while the cellular prion protein (PrP(C)) is presumed to be involved in the same process. Anchored to the outer side of the plasma membrane, this protein has the ability to bind copper ions and undergo internalization. To provide indications about the contribution of Ctr1 and PrP(C) proteins in cell copper transport, we used a fluorimetric method to characterize the kinetic properties of ion internalization in a neuroblastoma cell model, overexpressing prion protein (B104). Biochemical characteristics of intake delineated in the presence of other metal ions and an excess of extracellular potassium were compatible with PrP(C)-mediated endocytotic transport. Accordingly, inhibition of clathrin-dependent endocytosis by hypertonic shock and enzymatic removal of surface prion protein reduced copper influx by the same extent. On the whole, experimental evidence collected in a neuron-like cell model sustains a role for PrP(C) in mediating copper uptake by clathrin-dependent endocytosis. [ABSTRACT FROM AUTHOR]

Abstract  The present paper reported postmortem changes in muscle proteins on sea bream (Sparus aurata), during ice storage. The postmortem evolution of protein patterns in farmed sea bream was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimension electrophoresis (2DE). Matrix associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was used for identification of proteins. Results of the bio-informatics analysis demonstrate that: (1) the normalized volume of skeletal alpha-actin and tropomyosin is not affected by the time of storage; (2) the normalized volumes of myosin light chain 3 and of major histocompatibility complex (MHC) class II beta1 increase; (3) the normalized volumes of Sec 13-like and parvalbumin significantly decrease. [ABSTRACT FROM AUTHOR]

This article offers data about speciation of mercury and arsenic in the muscle of a small scyliorhinid shark, Scyliorhinus canicula, representing a vital link between invertebrates and larger fish, and discusses the results in relation to age/size of specimens. An overall analysis of the obtained results confirms that mercury is mainly present as organic form. From toxicological point of view, methylmercury concentrations are not to understate because toxic effects of this organic form of mercury are well known. In addition, high accumulation of organic arsenic in organisms deserve attention because it has been shown that an organic compound, dimethylarsinate, has carcinogenic potential.

Trace metal concentrations of mercury, cadmium, lead and chromium inPatella caerulea, andMullus barbatuswere investigated to provide information on pollution of Ionian Sea, since these metals have the highest toxic potential. High chromium levels (0.47-0.97 µg g-1 ww) were registered in limpet samples collected from two station near the Gulf of Taranto, while elevated concentration of mercury (0.31-1.50 µg g-1 ww) were found in mullet specimens from Sicily. The metal concentrations recorded at the clean stations may be considered as useful background levels to which to refer for comparison within the Mediterranean area. On the contrary, the high levels of chromium and mercury found respectively in the areas near the Gulf of Taranto and at Capo Passero being of concern in terms of environmental health need frequent monitoring. [ABSTRACT FROM AUTHOR]

This study demonstrates the existence of calcium channels in the apical membranes of the hepatopancreatic blister (B) cells of Marsupenaeus japonicus. Using brush-border membrane vesicles we demonstrated that the channel-mediated calcium passive flux was saturable and was stimulated by a transmembrane electrical potential difference and inhibited by barium. We raised a monoclonal antibody (Mab 24A4) against the calcium channel, which allowed us to inhibit the channel-mediated calcium uptake. By immunocytochemistry, using Mab 24A4, we demonstrated that these channels are located at the apical membrane of hepatopancreatic B cells. Finally, by measuring the calcium uptake in R- and B-enriched cell suspensions, we showed that only the plasma membrane of the B cells expresses a channel-mediated calcium uptake inhibited by barium, verapamil and the monoclonal antibody 24A4. The plasma membrane of R cells did not show calcium channels. [ABSTRACT FROM AUTHOR]

d-Glucose absorptive processes at the gastrointestinal tract of decapod crustaceans are largely under-investigated. We have studied Na+-dependent d-glucose transport (Na+/d-glucose cotransport) in the hepatopancreas of the Kuruma prawn, Marsupenaeus japonicus, using both brush-border membrane vesicles and purified R and B hepatopancreatic cell suspensions. As assessed by brush-border membrane vesicle studies, Na+/d-glucose cotransport was inhibited by phloridzin and responsive to the (inside negative) membrane potential. Furthermore, it was strongly activated by protons (although only in the presence of an inside-negative membrane potential), which correlates with the fact that the lumen of crustacean hepatopancreatic tubules is acidic. When assayed in purified R and B cell suspensions, Na+/d-glucose cotransport activity was restricted to B cells only. Mab 13, a monoclonal antibody recognizing an 80- to 85-KDa protein at the brush-border membrane location, inhibited Na+/D-glucose cotransport in brush-border membrane vesicles as well as in enriched B cell suspensions. Primers designed after comparison of highly homologous regions of various mammalian sodium-glucose transporter) nucleotide sequences failed to produce RT-PCR amplification products from Kuruma prawn hepatopancreatic RNA. The molecular nature of this Na+/d-glucose cotransport system is still to be established. [ABSTRACT FROM AUTHOR]

The goal of the present study was to evaluate the changes in the cell type composition and ATPase activities (total ATPase, ouabain-sensitive Na+/K+-ATPase, furosemide-sensitive Na+-ATPase) that occur during the different stages of the moulting cycle in the hepatopancreas of the Marsupenaeus japonicus. The results clearly suggest that the number of resorptive and fibrillar cell types changes significantly during the different stages. An inverse correlation between resorptive and fibrillar cells is observed during moulting (both in normally fed and fasted animals). Fasting, but not the moulting cycle, affects the number of blister-like cells. In the resorptive cells the enzymatic activities (total ATPases and ouabain-sensitive Na+/K+-ATPase) also change during the moulting in a cyclical manner. All these results are in agreement with and confirm the different functions carried out by the two cell types within the hepatopancreas. [ABSTRACT FROM AUTHOR]

This survey provides information on the levels of heavy metal, polychlorinated biphenyl and organochlorine pesticide residues in marine organisms to ascertain whether these concentrations exceeded the prescribed legal limits. In order to assess the potential human health impact, the weekly intake was estimated. Most of the organisms analysed showed higher levels of mercury than the maximum permissible limit, while cadmium and lead were below the proposed permissible limits in all samples. The estimated intake was far above the established Provisional Tolerable Weekly Intake for all metals, except for total mercury. [ABSTRACT FROM AUTHOR]

The article discusses the mercury speciation and relationship between mercury and selenium in liver of Galeus melastomus from the Mediterranean Sea. Among the toxic trace metals, mercury is one of the most hazardous environmental pollutants in the marine environment. The majority of the mercury released into the marine environment is inorganic but it can be converted to the methyl mercury form, by bacteria living in the sediment. The toxicology and environmental behaviour of mercury is quite complex, since the toxicity, mobility, and bioaccumulation of mercury depend on its chemical form.