Overestimation of Phonological Judgments on the Right Side of Space

Spatial attentional biases can be observed during the processing of linguistic material. For example, we previously reported that healthy subjects overestimate the semantic distance between word stimuli in the right vs. left space. Here, we explored whether or not attentional biases are also observed in tasks requiring an evaluation of phonological distance between words in the right and left hemifield. Forty-one healthy subjects were presented with triplets of words arranged in space and were asked to indicate the side of the space in which the phonological distance between the middle word and an outer word was smaller. In Experiment 1, real words and pseudowords were used, while in Experiment 2, only pseudowords and consonant strings were used. Subjects overestimated the phonological distance between the middle and outer words in the right space. These findings were specific to word stimuli. These results are consistent with the idea that semantic and phonological information may be internally mapped onto spatial representations

Role of pitrm1 in mitochondrial dysfunction and neurodegeneration

Mounting evidence shows a link between mitochondrial dysfunction and neurodegenerative disorders, including Alzheimer Disease. Increased oxidative stress, defective mitodynamics, and impaired oxidative phosphorylation leading to decreased ATP production, can determine synaptic dysfunction, apoptosis, and neurodegeneration. Furthermore, mitochondrial proteostasis and the protease-mediated quality control system, carrying out degradation of potentially toxic peptides and misfolded or damaged proteins inside mitochondria, are emerging as potential pathogenetic mechanisms. The enzyme pitrilysin metallopeptidase 1 (PITRM1) is a key player in these processes; it is responsible for degrading mitochondrial targeting sequences that are cleaved off from the imported precursor proteins and for digesting a mitochondrial fraction of amyloid beta (Aβ). In this review, we present current evidence obtained from patients with PITRM1 mutations, as well as the different cellular and animal models of PITRM1 deficiency, which points toward PITRM1 as a possible driving factor of several neurodegenerative conditions. Finally, we point out the prospect of new diagnostic and therapeutic approaches.publishedVersio

Macchine del Tempo/Time Machines Concept per la realizzazione di una grande mostra INAF nella città di Roma

La Mostra “Macchine del Tempo/Time Machines” sarà inaugurata a fine 2023, si chiuderà a Primavera del 2024 e verrà ospitata nel secondo piano del Palazzo delle Esposizioni di Roma, in Via Nazionale, gestito dall’Azienda Speciale Palaexpo, una partecipata del Comune di Roma, con cui sarà siglata una specifica convenzione. Il progetto ha un duplice obiettivo, da un lato realizzare una mostra pop che parli a tutti e che metta al centro l’Istituto Nazionale di Astrofisica, le sue persone e le sue ricerche, dall’altro dar vita a qualcosa di unico, che faccia parlare di sé e che incentivi il pubblico a informarsi sulle tematiche affrontate per ampliare il proprio sapere e conoscere INAF e i suoi osservatori distribuiti sul territorio italiano. Un percorso che vuole giocare tra il vecchio e il nuovo, con uno stile anni ’80, ma con contenuti che parlano dell’oggi e del domani e che usa il gioco come meccanismo per suscitare interesse ed emozione positiva. Le “Macchine del Tempo” sono strumenti dell’ingegno italiano, frutto della ricerca condotta negli osservatori dell’Istituto Nazionale di Astrofisica dalle donne e dagli uomini che ogni giorno mettono impegno e passione per portare le conoscenze umane sempre più distanti. Questa mostra vuole diffondere la conoscenza attuale facendo però vedere chi c’è “dietro l’oculare”. Un’esperienza immersiva che comincia da noi stessi e subito passa a Galileo, l’italiano che - inventando il cannocchiale - posò l’occhio sulla nostra prima “macchina del tempo”. Sarà importante realizzare un catalogo della mostra e sono stati avviati contatti per rendere l’esposizione fruibile al pubblico in modo quanto più possibile inclusivo. Nel corso del periodo in cui sarà visitabile la mostra saranno organizzati incontri scientifici di alto livello, con nomi di primo piano della Ricerca astrofisica e spaziale mondiale, ma anche aperitivi scientifici più informali, durante i quali i cittadini potranno conversare direttamente con i ricercatori. Verranno proposti dei progetti di public engagement che utilizzano format nuovi come il Poetry Slam abbinato a uno stage scientifico o rassegne cinematografiche che propongono film nei quali sono presenti strutturei INAF. Si intende inoltre realizzare uno show per planetario, in collaborazione con il Planetario di Roma, sul tema “Macchine del Tempo”, da programmare in un periodo vicino a quello della della mostra e da diffondere in seguito, anche sotto forma di film per planetario, sia in italiano che in altre lingue, per la fruizione da parte di un pubblico internazionale. La mostra “Macchine del Tempo” ha per INAF molteplici aspetti di ritorno in campo sociale, comunicativo e relazionale. La mostra vuole stimolare le giovani generazioni allo studio di materie STEM, ma con “contaminazioni” anche di altre discipline non solo scientifiche. Questo determinerà in futuro per INAF anche la possibilità di avere giovani risorse da inserire nell’organico di ricerca. L’astrofisica italiana è un'eccellenza internazionalmente riconosciuta e deve essere maggiormente valorizzata anche in Italia, per potenziare l’immagine che INAF trasmette ai cittadini, alle istituzioni e agli stakeholders, attraverso i finanziamenti pubblici rivolti alla ricerca, incentivando ad esempio le collaborazioni, o anche le donazioni, con altre realtà pubbliche o private. Questa mostra vuole essere un mezzo per offrire alle scuole del territorio, e non solo, la possibilità di accedere a un patrimonio culturale che unisce scienza, tecnologia e storia. Un patrimonio davvero unico nel suo genere. L’ambizione è di riuscire a realizzare un contenitore di eventi e di dibattiti che ruotino attorno ai temi più attuali dell’astrofisica, ma che non temono e che anzi cercano forti legami con l’arte tutta, dal teatro alla pittura, dalla musica alla letteratura

Leber's Hereditary Optic Neuropathy: A Report on Novel mtDNA Pathogenic Variants

Leber's hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA); 90% of cases harbor the m.3460G>A, m.11778G>A, and m.14484T>C primary mutations. Here, we report and discuss five families with patients affected by symptomatic LHON, in which we found five novel mtDNA variants. Remarkably, these mtDNA variants are located in complex I genes, though without strong deleterious effect on respiration in cellular models: this finding is likely linked to the tissue specificity of LHON. This study observes that in the case of a strong clinical suspicion of LHON, it is recommended to analyze the whole mtDNA sequence, since new rare mtDNA pathogenic variants causing LHON are increasingly identified

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non -responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy

Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis.

Biallelic mutations in NDUFAF6 have been identified as responsible for cases of autosomal recessive Leigh syndrome associated with mitochondrial complex I deficiency. Here we report two siblings and two unrelated subjects with Leigh syndrome, in which we found the same compound heterozygous missense (c.532G>C:p.A178P) and deep intronic (c.420+784C>T) variants in NDUFAF6. We demonstrated that the identified intronic variant creates an alternative splice site, leading to the production of an aberrant transcript. A detailed analysis of whole-exome sequencing data together with the functional validation based on mRNA analysis may reveal pathogenic variants even in non-exonic regions

Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Evaluation of Mitochondrial Dysfunction and Idebenone Responsiveness in Fibroblasts from Leber’s Hereditary Optic Neuropathy (LHON) Subjects

Leber’s hereditary optic neuropathy (LHON) is a disease that affects the optical nerve, causing visual loss. The diagnosis of LHON is mostly defined by the identification of three pathogenic variants in the mitochondrial DNA. Idebenone is widely used to treat LHON patients, but only some of them are responders to treatment. In our study, we assessed the maximal respiration rate (MRR) and other respiratory parameters in eight fibroblast lines from subjects carrying LHON pathogenic variants. We measured also the effects of idebenone treatment on cell growth and mtDNA amounts. Results showed that LHON fibroblasts had significantly reduced respiratory parameters in untreated conditions, but no significant gain in MRR after idebenone supplementation. No major toxicity toward mitochondrial function and no relevant compensatory effect in terms of mtDNA quantity were found for the treatment at the tested conditions. Our findings confirmed that fibroblasts from subjects harboring LHON pathogenic variants displayed impaired respiration, regardless of the disease penetrance and severity. Testing responsiveness to idebenone treatment in cultured cells did not fully recapitulate in vivo data. The in-depth evaluation of cellular respiration in fibroblasts is a good approach to evaluating novel mtDNA variants associated with LHON but needs further evaluation as a potential biomarker for disease prognosis and treatment responsiveness