Longitudinal study of clinical and neurophysiological features in essential tremor

Background and purpose: Essential tremor (ET) is a common and heterogeneous disorder characterized by postural/kinetic tremor of the upper limbs and other body segments and by non-motor symptoms, including cognitive and psychiatric abnormalities. Only a limited number of longitudinal studies have comprehensively and simultaneously investigated motor and non-motor symptom progression in ET. Possible soft signs that configure the ET-plus diagnosis are also under-investigated in follow-up studies. We aimed to longitudinally investigate the progression of ET manifestations by means of clinical and neurophysiological evaluation. Methods: Thirty-seven ET patients underwent evaluation at baseline (T0) and at follow-up (T1; mean interval +/- SD = 39.89 +/- 9.83 months). The assessment included the clinical and kinematic evaluation of tremor and voluntary movement execution, as well as the investigation of cognitive and psychiatric disorders. Results: A higher percentage of patients showed tremor in multiple body segments and rest tremor at T1 as compared to T0 (all p-values < 0.01). At T1, the kinematic analysis revealed reduced finger-tapping movement amplitude and velocity as compared to T0 (both p-values < 0.001). The prevalence of cognitive and psychiatric disorders did not change between T0 and T1. Female sex, absence of family history, and rest tremor at baseline were identified as predictive factors of worse disease progression. Conclusions: ET progression is characterized by the spread of tremor in multiple body segments and by the emergence of soft signs. We also identified possible predictors of disease worsening. The results contribute to a better understanding of ET classification and pathophysiology

Intestinal Permeability is Increased in Children Born Preterm, with Persistent Growth Delay and Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a clinical condition in which foetus cannot develop its own growth potential..

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab. After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial results. Regarding adverse events, our cohort experienced a toxicity profile similar to the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival (PFS) was 7 months, shorter than that observed in the ELOQUENT-3, probably due to the different clinical characteristics of the two cohorts. Interestingly, the ISS stage III (HR:2.55) was associated with worse PFS. Finally, our series's median overall survival (OS) was shorter than that observed in the ELOQUENT-3 trial (17.5 versus 29.8 months). In conclusion, our real-world study confirms EloPd as a safe and possible therapeutic choice for RRMM who received at least two prior therapies, including lenalidomide and a PI

Why do you like Arcimboldo's portraits? Effect of perceptual style on aesthetic appreciation of ambiguous artworks

Visual aesthetic experience reflects the states of the mind and the brain when visual artworks are being viewed. In the present study, we investigated whether perceptual style affects the aesthetic appreciation of ambiguous artworks, such as those of Arcimboldo, which are characterized by part-whole ambiguity. Participants were classified as having a global or local perceptual style and were asked to aesthetically judge two different types of artworks: portraits by Arcimboldo and by Renaissance painters. We found that perceptual style affected both the aesthetic appreciation and the degree of perceived ambiguity in Arcimboldo's artworks. Our findings suggest that aesthetic judgment is a consequence of the interaction between individual personal perceptual style and the perceptual features of artworks

RAB7A Regulates Vimentin Phosphorylation through AKT and PAK

RAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin domains interacting with RAB7A. As several kinases could be responsible for vimentin phosphorylation, we investigated whether modulation of RAB7A expression affects the activity of these kinases. We discovered that RAB7A regulates AKT and PAK1, and we demonstrated that increased vimentin phosphorylation at Ser38 (Serine 38), observed upon RAB7A overexpression, is due to AKT activity. As AKT and PAK1 are key regulators of several cellular events, we investigated if RAB7A could have a role in these processes by modulating AKT and PAK1 activity. We found that RAB7A protein levels affected beta-catenin and caspase 9 expression. We also observed the downregulation of cofilin-1 and decreased matrix metalloproteinase 2 (MMP2) activity upon RAB7A silencing. Altogether these results demonstrate that RAB7A regulates AKT and PAK1 kinases, affecting their downstream effectors and the processes they regulate, suggesting that RAB7A could have a role in a number of cancer hallmarks

Cumulative radiation exposure from radiological imaging in patients with Hodgkin and diffuse large b-cell lymphoma not submitted to radiotherapy

Objective: To assess the cumulated exposure to radiation due to imaging in Hodgkin (HL) and diffuse large B-cell (DLBCL) lymphoma patients who were not submitted to radiotherapy. Methods: The study population included 51 and 83 adult patients with HL and DLBCL, with a follow-up duration >1 year. The cumulated exposure was expressed using patient-specific data as cumulated effective dose (CED). Results: Fifty-one HL patients (median age 47 years) were followed for a median of 3.5 years. The median total CED per subject was 104 mSv. CT and PET/CT examinations accounted for 75 and 25% of the total CED, respectively. 26 patients (49%) had a total CED ≥ 100 mSv and the maximum CED was 302 mSv. Eighty-three DLBCL patients (median age 66 years) were followed for a median of 3.7 years. The median total CED per subject over the study period was 134 mSv. CT and PET/CT for 86% and 13% of the total CED, respectively. 56 patients (67%) had a total CED ≥100 mSv. The maximum CED was 557 mSv. Conclusion: Our study demonstrated the large number of imaging procedures performed for patients with lymphoma. Overall, 61% of the patients accrued a CED ≥ 100 mSv. Imaging policies were only in a partial agreement with current international guidelines. Advances in knowledge: The cumulated exposure radiation exposure may be of concern in HL patients and the contribution of CT procedures to the total CED is significant. The standardisation of clinical guidelines for managing patients with lymphoma is warranted

Intestinal Permeability in Children with Functional Gastrointestinal Disorders: The Effects of Diet

Functional gastrointestinal disorders (FGIDs) are very common and life-impacting in children and young adults, covering 50% of pediatric gastroenterologist consultations. As it is known, FGIDs may be due to alterations in the gut–brain axis, dysbiosis and dysregulation of intestinal barrier, causing leaky gut. This may enhance increased antigen and bacterial passage through a damaged mucosa, worsening the impact of different medical conditions such as FGIDs. Little is known about the role of nutrients in modifying this “barrier disruption”. This narrative review aims to analyze the clinical evidence concerning diet and Intestinal Permeability (IP) in FGIDs in children. We searched the PubMed/Medline library for articles published between January 2000 and November 2021 including children aged 0–18 years old, using keywords related to the topic. Since diet induces changes in the intestinal barrier and microbiota, we aimed at clarifying how it is possible to modify IP in FGIDs by diet modulation, and how this can impact on gastrointestinal symptoms. We found that) is that small changes in eating habits, such as a low-FODMAP diet, an adequate intake of fiber and intestinal microbiota modulation by prebiotics and probiotics, seem to lead to big improvements in quality of life

Progetto Nazionale PRIN - Qualit\ue0 della ricerca e documentazione scientifica nelle scienze pedagogiche

Caldin R. fa parte dell'unit\ue0 coordinata da Luigi d'Alonzo La discussione internazionale in corso sulla ricerca scientifica in educazione, istruzione e formazione chiede di collegare sempre pi\uf9 visibilmente l'impostazione di politiche e pratiche scolastiche a prove fondate scientificamente, che possano essere verificate e confutate. Il miglioramento della qualit\ue0 della ricerca nelle scienze pedagogiche si consegue, infatti, fornendo risultati probanti di natura causale, comunque rigorosamente argomentati; nonch\ue9 assicurando la diffusione e l'utilizzo sistematico di indicatori di qualit\ue0 comparabili e interfacciabili con quelli adottati da altri settori della ricerca scientifica sia nazionale che internazionale. Da tempo, in ambito internazionale, si \ue8 proceduto a standardizzare l'adozione di metodologie di ricerca e di intervento impostati in funzione di questo obiettivo, privilegiando in particolare protocolli multivariati e multireferenziali di ricerca nonch\ue9 l'analisi comparata e sistematica delle ricerche condotte sullo stesso tema (meta-analisi). Con questo progetto si avvia, per la prima volta, nella storia della ricerca pedagogica italiana, un'azione di sistema che intende attivare una rete nazionale intersettoriale delle scienze pedagogiche con l'obiettivo di porre a disposizione della comunit\ue0 scientifica pedagogica nazionale sistemi di documentazione e di metadatazione nonch\ue9 motori di ricerca, comparabili ed interfacciabili con quelli in uso in altri ambiti disciplinari, in modo da assicurare accessibilit\ue0, comparazione sistematica delle qualit\ue0 e ricerca pubblica sui risultati della ricerca scientifica. Si intende avviare, cio\ue8, una operazione di ricostruzione delle ontologie delle Scienze della Educazione e della Formazione che consenta di acquisire rappresentazioni e mappe concettuali dei diversi domini implicati dalla ricerca, sperimentando peraltro e ottimizzando risultati e strumentazioni Open Access e Open Culture gi\ue0 acquisite da singoli Gruppi locali in precedenti attivit\ue0 di ricerca sul web semantico e sui motori di metadatazione . Gli aspetti metodologici, costitutivi del dialogo tra ricerca empirica e ricerca storico-teorica, rendono urgente e inderogabile la stipulazione di protocolli di indagine condivisi per favorire la critica e la crescita della conoscenza pedagogica e per fertilizzare il miglioramento delle pratiche educative e formative

The incidence of cardiovascular events in Italian patients with systemic lupus erythematosus is lower than in North European and American cohorts: Implication of disease-associated and traditional risk factors as emerged by a 16-year retrospective GIRRCS study

Previous study from our group has pointed out a lower number of cardiovascular (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Clinical charts of SLE patients consecutively admitted to 5 Italian rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV events at baseline were retrospectively studied. CV cumulative incidence (ie, the proportion of patients who experienced a new CV event over the follow-up period) and CV incidence rate (ie, the number of events in the cohort divided by the total number of years at risk) were evaluated. The detected incidences were compared with those reported in SLE cohorts from other countries. The median duration of follow-up was 6 years (IQR=3-11). During the observational period, 37 (cumulative incidence=7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years. The CV cumulative incidence and incidence rate detected in our Italian cohort were lower than those from most North European and American cohorts, characterized by a high impact of traditional risk factors. Nevertheless, the cumulative incidence was similar to that reported in a Spanish cohort with a high frequency of traditional risk factors (geographic impact), while the incidence rate was only slightly higher than that in the Baltimore cohort, which is characterized by a strict follow-up of patients (medical impact). Our results confirmed that Italian lupus patients have a low incidence of CV events. Moreover, the geographic origin, traditional risk factors, and medical approach appear to have an impact on CV disease in SLE. Abbreviations: ACR = American College of Rheumatology, aPL = antiphospholipid antibody, ASA = aspirin, CV = cardiovascular, HCQ = hydroxychloroquine, SCORE = Systematic COronary Risk Evaluation, SLE = systemic lupus erythematosus