135 research outputs found
“La lingua è un reame che si prende gioco degli imperi”: Paul Celan e l’idea di un umanesimo transnazionale
No full textIl saggio analizza il complesso rapporto del poeta di origini ebraiche Paul Celan con la lingua tedesca, sua sola lingua poetica, e la questione dell'identità nazionale di un poeta definito, da molti e da se stesso, austriaco, tedesco, francese, rumeno. Al centro dell'analisi vi è il carteggio del poeta con la moglie, l'artista francese Gisèle Celan-Lestrange
sj-docx-1-msj-10.1177_13524585231199820 – Supplemental material for Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis
No full textSupplemental material, sj-docx-1-msj-10.1177_13524585231199820 for Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis by Sarah Lena Susanna Jacober, Giulio Disanto, Rosaria Sacco, Delania Meng, Giulia Mallucci, Ursula Candrian, Sebastiano Semini, Massimiliano Tiberti, Claudio Gobbi and Chiara Zecca in Multiple Sclerosis Journal</p
MSJ885613_supplemental_material – Supplemental material for Neurofilament light levels are associated with long-term outcomes in multiple sclerosis
No full textSupplemental material, MSJ885613_supplemental_material for Neurofilament light levels are associated with long-term outcomes in multiple sclerosis by Jens Kuhle, Tatiana Plavina, Christian Barro, Giulio Disanto, Dipen Sangurdekar, Carol M Singh, Carl de Moor, Bob Engle, Bernd C Kieseier, Elizabeth Fisher, Ludwig Kappos, Richard A Rudick and Jaya Goyal in Multiple Sclerosis Journal</p
Il ritratto di Lulu. Da Frank Wedekind a Georg Wilhelm Pabst
No full textThis essay focuses on Lulu by Frank Wedekind. The drama was developed from an idea conceived by the author dating back to the nineties of the Nineteenth Century and is characterised by a series of complex incidents of censorship and those of a textual origin. The drama is discussed with relation to its film version by Georg Wilhelm Pabst dated 1929. This comparative perspective allows for unexplored elements of both works to be rediscovered since both revolve around the concept of image, thereby highlighting the importance of the Wedekind literary model for the director, Pabst, as well as the presence of the famous playwright’s almost avant-garde elements within the scope of modernist literature. / Il saggio è dedicato alla Lulu di Frank Wedekind. Il dramma, sviluppato a partire da un’idea dello scrittore risalente agli anni novanta dell’Ottocento e segnato da complesse vicende di genesi testuale e di censura, viene discusso in relazione alla sua versione cinematografica di Georg Wilhelm Pabst del 1929. Il confronto fra le due opere permette di riscoprire aspetti inesplorati di entrambe le opere, poiché entrambe si incentrano sul concetto di immagine, ed evidenzia così l’importanza del modello letterario Wedekind per il regista Pabst come anche la presenza di elementi quasi d’avanguardia nel noto drammaturgo della literarische Moderne
Protein-protein interaction analysis highlights additional loci of interest for multiple sclerosis
No full textGenetic factors play an important role in determining the risk of multiple sclerosis (MS). The strongest genetic association in MS is located within the major histocompatibility complex class II region (MHC), but more than 50 MS loci of modest effect located outside the MHC have now been identified. However, the relative candidate genes that underlie these associations and their functions are largely unknown. We conducted a protein-protein interaction (PPI) analysis of gene products coded in loci recently reported to be MS associated at the genome-wide significance level and in loci suggestive of MS association. Our aim was to identify which suggestive regions are more likely to be truly associated, which genes are mostly implicated in the PPI network and their expression profile. From three recent independent association studies, SNPs were considered and divided into significant and suggestive depending on the strength of the statistical association. Using the Disease Association Protein-Protein Link Evaluator tool we found that direct interactions among genetic products were significantly higher than expected by chance when considering both significant regions alone (p<0.0002) and significant plus suggestive (p<0.007). The number of genes involved in the network was 43. Of these, 23 were located within suggestive regions and many of them directly interacted with proteins coded within significant regions. These included genes such as SYK, IL-6, CSF2RB, FCLR3, EIF4EBP2 and CHST12. Using the gene portal BioGPS, we tested the expression of these genes in 24 different tissues and found the highest values among immune-related cells as compared to non-immune tissues (p<0.001). A gene ontology analysis confirmed the immune-related functions of these genes. In conclusion, loci currently suggestive of MS association interact with and have similar expression profiles and function as those significantly associated, highlighting the fact that more common variants remain to be found to be associated to MS
Natalizumab in spinal multiple sclerosis in a daily clinical setting
No full textObjective: We aimed to investigate the influence of natalizumab (NTZ) treatment on multiple sclerosis course in patients with and without spinal involvement.Methods: Annualized relapse rate (ARR), disability progression and occurrence of new brain and spinal T2 lesions (N2TL) in 68 spinal (S-P) versus 68 non-spinal matched patients (NS-P) were retrospectively collected and compared between before (2 years) and after NTZ treatment using multivariate regression models.Results: Mean duration of NTZ treatment was 31.3 ± 16.3 months in S-P and 32.1 ± 15.1 months in N-SP (p = 0.56). The mean ARR after NTZ treatment was similarly reduced in both S-P (0.07 ± 0.19) and N-SP (0.07 ± 0.16) (p < 0.001 for both). Disability progression after NTZ start was similarly low in S-P and NS-P. However, when compared to before NTZ start, disability progression was significantly reduced in S-P (p = 0.017), but not in NS-P (p = 0.68). This was largely mediated by a higher disability progression before NTZ start in S-P than N-SP. The risk of developing N2TL during NTZ was not different between S-P and NS-P (p = 0.10).Conclusions: NTZ similarly reduced the occurrence of relapses and NT2L in S-P and NS-P, whereas the effect on disability progression was particularly evident in the presence of spinal involvement. NTZ appears to be a treatment of high efficacy in both S-P and NS-P
Monitoring of safety and effectiveness of cladribine in multiple sclerosis patients over 50 years
No full textClinical trial data regarding efficacy and safety of cladribine in MS are limited to young individuals, and the overall risk-benefit profile does not necessarily applies to elderly patients. We investigated effectiveness and safety outcomes in MS patients initiating cladribine at ≥50 years (n=35) and <50 years (n=62), over a median follow-up of 12.4 months. There were no differences in time to evidence of disease activity (HR=0.73, 95%CI=0.18-2.91, p=0.657), post-treatment lymphocyte counts (β=0.24, p=0.825) or occurrence of adverse events (OR=0.84, 95%CI=0.24-2.93, p=0.791) between age groups. Female sex and greater disability were associated with higher risk of adverse events (especially infections). These limited data do not suggest safety concerns regarding use of cladribine in elderly MS
Adherence to Medication in Neurogeriatric Patients: Insights from the NeuroGerAd Study
No full textNonadherence to medication is associated with increased morbidity, mortality, and healthcare costs, especially in older adults with higher chances of multimorbidity. However, comprehensive data on factors influencing adherence in this patient group are rare. Thus, data for 910 patients were acquired, including demographic data, nonadherence (Stendal Adherence to Medication), depression (Beck Depression Inventory), cognition (Montreal Cognitive Assessment), personality (Big Five Inventory), satisfaction with healthcare (Health Care Climate Questionnaire), quality of life (36-item Short Form Survey), mobility, diagnoses, and medication. Elastic net regularization was used to analyze the predictors of adherence. Principal component and general estimation equations were calculated to analyze the underlying patterns of adherence. Only 21.1% of patients were fully adherent. Nonadherence was associated with male gender, higher number of medications, diagnosis, depression, poor patient–physician relationship, personality, impaired cognition, and impaired mobility. Nonadherence was classified into three sub-factors: forgetting (46.2%), missing knowledge about medication (29%), and intentional modification of medication (24.8%). While depression exerted the strongest influence on modification, a high number of medications was associated with missing knowledge. The different patterns of nonadherence (i.e., modification, missing knowledge, and forgetting) are influenced differently by clinical factors, indicating that specific approaches are needed for interventions targeting adherence
Genetic and environmental factors influencing susceptibility to the complex disease multiple sclerosis
No full textMultiple sclerosis is a complex immune mediated condition of the central nervous system characterized by myelin loss and progressive neurodegeneration. The risk of developing MS is influenced by both genetic and environmental agents and, among them, several lines of evidence support a role for vitamin D deficiency, Epstein-Barr virus (EBV) infection and smoking in the aetiology of this disease. The aim of this work was to further elucidate how nature and nurture act in the causal cascade leading to MS. In chapter 1, I show that the main genetic factor in adult MS (the HLA-DRB1*1501 allele) plays an equally important role in paediatric cases of MS (PMS) and that EBV negative PMS patients represent a separate entity characterized by lower age at disease onset, lower female to male ratio and a trend towards a lower frequency of the HLA-DRB1*1501 allele. In chapter 2, I provide evidence in support of month of birth having a role on MS risk and T cell production and that vitamin D may underlie this effect. In chapter 3 I demonstrate the presence of a link between vitamin D deficiency and the immune response against EBV, whereby the proportion of EBV seropositive MS patients and controls increases with increasing latitude and high dose vitamin D supplementation appears to reduce the level of antibodies against this virus. In chapter 4, I show that MS associated genetic variants are located in genomic regions that exert a regulatory function and are active in immune cell types. In chapter 5, I illustrate how vitamin D receptor binding is also located within active regulatory regions in immune cells and that this is particularly evident near MS associated genes. Finally, in chapter 6, I use chromatin data on more than 100 different cell types and conclude that MS associated genetic variants are particularly active in T helper, T cytotoxic and B cells. Further work is needed to elucidate how genetic and environmental agents play a role in the cause of MS and to develop effective strategies for disease treatment and prevention
Two decades of subcutaneous glatiramer acetate injection: current role of the standard dose, and new high-dose low-frequency glatiramer acetate in relapsing–remitting multiple sclerosis treatment
No full textMatteo Caporro, Giulio Disanto, Claudio Gobbi, Chiara Zecca Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland Abstract: Glatiramer acetate, a synthetic amino acid polymer analog of myelin basic protein, is one of the first approved drugs for the treatment of relapsing–remitting multiple sclerosis. Several clinical trials have shown consistent and sustained efficacy of glatiramer acetate 20 mg subcutaneously daily in reducing relapses and new demyelinating lesions on magnetic resonance imaging in patients with relapsing–remitting multiple sclerosis, as well as comparable efficacy to high-dose interferon beta. Some preclinical and clinical data suggest a neuroprotective role for glatiramer acetate in multiple sclerosis. Glatiramer acetate is associated with a relatively favorable side-effect profile, and importantly this was confirmed also during long-term use. Glatiramer acetate is the only multiple sclerosis treatment compound that has gained the US Food and Drug Administration pregnancy category B. All these data support its current use as a first-line treatment option for patients with clinical isolated syndrome or relapsing–remitting multiple sclerosis. More recent data have shown that high-dose glatiramer acetate (ie, 40 mg) given three times weekly is effective, safe, and well tolerated in the treatment of relapsing–remitting multiple sclerosis, prompting the approval of this dosage in the US in early 2014.This high-dose, lower-frequency glatiramer acetate might represent a new, more convenient regimen of administration, and this might enhance patients’ adherence to the treatment, crucial for optimal disease control. Keywords: glatiramer acetate, disease modifying treatment, efficacy, safet
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