SOD1, from Bench to Bed: New Role for the Oldest Protein Implicated in ALS

In 1993, the first superoxide dismutase 1 (SOD1) mutation in amyotrophic lateral sclerosis (ALS) patients has been described by Rosen et al. successively, the scientific literature focused on the role of SOD1 in the pathogenesis of ALS. While a clear genetic scenario has been presented, heterogeneous data have been formulated regarding transcriptional and post-transcriptional regulation of SOD1 so far. In particular, the dilemma concerns the SOD1 protein expression, in the direction of a loss of function of the wild-type SOD1 or a toxic gain of function of the altered SOD1, both in FALS (mutant-SOD1) and in SALS (misfolded-SOD1). In this chapter, we focus on the evolution of scientific knowledge about SOD1 protein in ALS patients, reviewing in detail the results obtained using peripheral blood cells in this research field. To conclude, we propose a brief summary of the described clinical correlation and discuss the possible SOD1 implication as a biomarker of ALS

Editorial

Após o número duplo XIX-XX da Revista de Italianística, dedicado à literatura italiana, apresentamos agora o número XXI-XXII que, respeitando a tradicional alternância da revista, aborda temas ligados à língua italiana.Para essa edição que, como a anterior, sai apenas em formato digital, selecionamos artigos da esfera dos estudos linguísticos e do ensino/aprendizagem de línguas não maternas, que focam o italiano e suas relações com o Brasil. Contribuíram à realização desse número pesquisadores brasileiros e italianos que estabelecem um diálogo de perspectivas teóricas sobre a linguagem e o ensino e nos oferecem estímulos para a reflexão nessas áreas de estudo e atuação

Managing female urinary incontinence: A regional prospective analysis of cost-utility ratios (curs) and effectiveness

Introduction: To evaluate the cost-utility of incontinence treatments, particularly anticholinergic therapy, by examining costs and quality-adjusted life years. Materials and methods: A prospective cohort study of women who were consecutively referred by general practitioners (GPs) to the Urology Department because of urinary incontinence. The primary outcome was evaluation of the cost-utility of incontinence treatments (surgery, medical therapy and physiotherapy) for stress and/or urgency incontinence by examining costs and quality-adjusted life years. Results: 137 consecutive female patients (mean age 60.6 ± 11.6; range 36-81) were enrolled and stratified according to pathologies: SUI and UUI. Group A: SUI grade II-III: 43 patients who underwent mid-urethral sling (MUS); Group B: SUI grade I-II 57 patients who underwent pelvic floor muscle exercise and Group C: UUI: 37 patients who underwent antimuscarinic treatment with 5 mg solifenacin daily. The cost utility ratio (CUR) was estimated as saving more than €1200 per QALY for surgery and physiotherapy and as costing under € 100 per QALY for drug therapy. Conclusions: This study shows that appropriate diagnosis and treatment of a patient with incontinence lowers National Health Service costs and improves the benefits of treatment and quality of life

Can daily intake of aspirin and/or statins influence the behavior of non-muscle invasive bladder cancer? A retrospective study on a cohort of patients undergoing transurethral bladder resection

Background: This study aimed to evaluate the behavior of non-muscle-invasive bladder cancer (NMIBC) in patients submitted to transurethral bladder resection (TURB) comparing subjects in chronic therapy with aspirin, statins, or both drugs to untreated ones. Methods: This retrospective study was conducted on 574 patients diagnosed with NMIBC who underwent TURB between March 2008 and April 2013. The study population was divided into two main groups: treated (aspirin and/or statins) and untreated. The treated group was further divided into three therapeutic subgroups: Group A (100 mg of aspirin, daily for at least two years); Group B (20 mg or more of statins, daily for at least two years); and Group C (100 mg of aspirin and 20 mg of statins together). The mean follow-up of patients was 45.06 months. Results: No significant differences were observed among the different groups at baseline. On multivariate analysis, statin treatment, smokers and high stage disease (T1) achieved the level of independent risk factor for the occurrence of a recurrence. When patients were stratified according to the different treatment; patients treated with statins (Group B) presented an higher rate of failure (56/91 patients; 61.5%) when compared to Group A (42/98 patients; 42.9%), Group C (56/98; 57.1%) and (133/287 patients; 46.3%). This difference corresponds to a significant difference in recurrence failure free survival (p = 0.01). Conclusions: Our results suggest that long-term treatment with aspirin in patients with NMIBC might play a role on reducing the risk of tumor recurrence. In contrast, in our investigation data from statins and combination treatment groups showed increased recurrence rates. A long-term randomized prospective study could definitively assess the possible role of this widely used drugs in NMIBC

Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder

The historical view that Amyotrophic Lateral Sclerosis (ALS) as a pure motor disorder has been increasingly challenged by the discovery of cognitive and behavioral changes in the spectrum of Frontotemporal Dementia (FTD). Less recognized and still significant comorbidities that ALS patients may present are prior or concomitant psychiatric illness, such as psychosis and schizophrenia, or mood disorders. These non-motor symptoms disturbances have a close time relationship with disease onset, may constitute part of a larger framework of network disruption in motor neuron disorders, and may impact ALS patients and families, with regards to ethical choices and end-of-life decisions. This review aims at identifying the most common psychiatric alterations related to ALS and its prognosis, looking at a common genetic background and shared structural brain pathology

Case report: p.Glu134del SOD1 mutation in two apparently unrelated ALS patients with mirrored phenotype

With upcoming personalized approaches based on genetics, it is important to report new mutations in amyotrophic lateral sclerosis (ALS) genes in order to understand their pathogenicity and possible patient responses to specific therapies. SOD1 mutations are the second most frequent genetic cause of ALS in European populations. Here, we describe two seemingly unrelated Italian patients with ALS carrying the same SOD1 heterozygous c.400_402 deletion (p.Glu134del). Both patients had spinal onset in their lower limbs, progressive muscular weakness with respiratory involvement, and sparing bulbar function. In addition to the clinical picture, we discuss the possible pathogenic role of this unfamiliar SOD1 mutation