Age-dependent changes in TDP-43 levels in a mouse model of Alzheimer disease are linked to Aβ oligomers accumulation

<p>Abstract</p> <p>Background</p> <p>Transactive response DNA-binding protein 43 (TDP-43) is the pathological protein found in frontotemporal lobar degeneration with ubiquitin positive inclusions and in amyotrophic lateral sclerosis. In diseased tissue, TDP-43 translocates from its physiological nuclear location into the cytoplasm, where it accumulates. Additionally, C-terminal fragments of TDP-43 accumulate in affected brain regions and are sufficient to cause TDP-43 mislocalization and cytoplasmic accumulation <it>in vitro</it>. TDP-43 also accumulates in 30% of Alzheimer disease (AD) cases, a finding that has been highly reproducible. The role of TDP-43 in AD and its relation with Aβ and tau pathology, the two neuropathological hallmarks of AD, remains to be elucidated.</p> <p>Results</p> <p>Here we show that levels of TDP-43 and its ~35 kDa C-terminal fragment are significantly increased in the 3×Tg-AD mice, an animal model of AD that develops an age-dependent cognitive decline linked to the accumulation of Aβ and tau. We also report that the levels of TDP-43 and its C-terminal fragment correlate with the levels of soluble Aβ oligomers, which play a key role in AD pathogenesis. Notably, genetically reducing Aβ₄₂production restores the levels of TDP-43 and its ~35 kDa C-terminal fragment to control levels.</p> <p>Conclusions</p> <p>These data suggest a possible relation between Aβ oligomers and TDP-43.</p

The Benefit of Sleeve Gastrectomy in Obese Adolescents on Nonalcoholic Steatohepatitis and Hepatic Fibrosis

Objective To determine whether bariatric surgery is effective for the treatment of nonalcoholic steatohepatitis (NASH) in adolescence, we compared the efficacy of laparoscopic sleeve gastrectomy (LSG) with that of lifestyle intervention (nonsurgical weight loss [NSWL]) for NASH reversal in obese adolescents. Study design Obese (body mass index ≥ 35 kg/m2) adolescents (13-17 years of age) with biopsy-proven NAFLD underwent LSG, lifestyle intervention plus intragastric weight loss devices (IGWLD), or only NSWL. At baseline and 1 year after treatment, patients underwent clinical and psychosocial evaluation, blood tests, liver biopsy, polysomnography, and 24-hour ambulatory blood pressure estimation. Results Twenty patients (21%) underwent LSG, 20 (21%) underwent IGWLD, and 53 (58%) received lifestyle intervention alone (NSWL). One year after treatment, patients who underwent LSG lost 21.5% of their baseline body weight, whereas patients who underwent IGWLD lost 3.4%, and patients who underwent NSWL increase 1.7%. In patients who underwent LSG, NASH reverted completely in all patients and hepatic fibrosis stage 2 disappeared in 18 patients (90%). After IGWLD, NASH reverted in 6 patients (24%) and fibrosis in 7 (37%). Patients who received the NSWL intervention did not improve significantly. Hypertension resolved in all patients who underwent LSG with preoperative hypertension (12/12) versus 50% (4/8) of the patients who underwent IGWLD (P = .02). The cohort-specific changes in impaired glucose metabolism were similar: 100% (9/9) of affected patients who underwent LSG versus 50% (1/2) of patients who underwent IGWLD (P = .02). LSG was also more affective in resolving dyslipidemia (55% [7/12] vs 26% [10/19]; P = .05) and sleep apnea (78% [2/9] vs 30% [11/20]; P = .001). Conclusion LSG was more effective than lifestyle intervention, even when combined with intragastric devices, for reducing NASH and liver fibrosis in obese adolescents after 1 year of treatment

A Virtual Reality Etruscan Museum Exhibition–Preliminary Results Of The Participants’ Experience

The current global health emergency has posed the need to reflect upon how to guarantee high standard of quality in 100% virtual exhibition. In this case study, we present one of the possible solutions to design a VR museum exhibition for educational purposes. The Centre for Museum Studies designed “The E-Trouria App”, a VR exhibition which is aimed at providing participants with personalised learning path based on an Etruscan museum collection in Rome. The App was designed by combining different pedagogical methods such as Digital Storytelling and Reflective Questioning. The goals of the research were to understand visitors' evaluation of their experience. 20 postgraduate students (F = 17; M = 3; Average age = 36 years) in Museum Education took part in the pre-pilot experimentation. Participants expressed very positive evaluation on the visit and their features (narratives, soundtrack and multimodality). Participants were emotionally engaged during the visit and the most reported emotions were “pleasure” and “wondering”. Future research steps are illustrated

Transient Waterhouse-Friderichsen Syndrome in a Child: A Case Report

Waterhouse-Friderichsen syndrome (WFS) is a rare but usually fatal disease characterized by adrenal insufficiency associated to bilateral adrenal hemorrhage. It can be associated both to non-infection and a variety of infectious diseases, among which sepsis from Neisseria meningitidis accounts for more than 80% of cases. We report the case of an otherwise healthy 2-year-old child who had a WFS as a consequence of Neisseria meningitidis infection and in which we witnessed a complete recovery of adrenal function a few months after the event. The case highlights not only the difficulty of diagnosing this syndrome but also, at the same time, the extreme importance of high suspicion, early treatment, a multidisciplinary approach and, most of all, the importance of verifying the restoration of adrenal function in order to achieve a better quality of life. Int J Clin Pediatr. 2021;10(1):28-33 doi: https://doi.org/10.14740/ijcp42

Hereditary Transthyretin Amyloidosis: How to Differentiate Carriers and Patients Using Speckle-Tracking Echocardiography

Background: Hereditary transthyretin amyloidosis is a rare disease caused by transthyretin (TTR) gene mutations. The aim of our study was to identify early signs of cardiac involvement in patients with a TTR gene mutation in order to differentiate carriers from patients with neurological or cardiac disease. Methods: A case-control study was carried out on 31 subjects with the TTR mutation. Patients were divided into three groups: 23% with cardiac amyloidosis and polyneuropathy (group A), 42% with only polyneuropathy (group B) and 35% carriers (group C). Speckle-tracking echocardiography (left-ventricular global longitudinal strain-GLS, atrial stiffness) was performed in all patients. The apical/basal longitudinal strain ratio (SAB) and relative apical sparing (RAS) were assessed in all subjects. Results: Analyzing groups C and B, we only found a significant difference in the SAB (p-value 0.001) and RAS (p-value 0.039). These parameters were significantly more impaired in group A compared to group B (SAB p-value 0.008; RAS p-value 0.002). Also, atrial stiffness was significantly impaired in groups A and B compared to group C. Conclusions: Our study suggests the diagnostic role of the SAB and RAS in cardiac amyloidosis. The SAB and RAS showed a gradual increase from carriers to patients with neurological and cardiac diseases. Thus, these parameters, in addition to atrial stiffness, could be used to monitor carriers. More extensive data are needed

Methylene blue reduces aβ levels and rescues early cognitive deficit by increasing proteasome activity

Promising results have emerged from a phase II clinical trial testing methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduces Aβ levels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin- and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action

Sollecitare il Pensiero critico al museo attraverso la realizzazione di infografiche. L’esperienza del progetto INTERACT

La ricerca di seguito descritta è stata condotta in seno al progetto INTERACT (Percorsi INTERattivi per l’Accessibilità museale e la fruizione del patrimonio culTurale), realizzato nell’ambito del Dipartimento di Scienze della Formazione dell’Università degli Studi Roma Tre e mirato a promuovere la creazione di nuovi sistemi d’inclusione sociale e di sviluppo della cittadinanza attiva all’interno dei musei, attraverso il coinvolgimento di diverse categorie di visitatori, in particolare studenti della scuola primaria e secondaria di secondo grado. Nelle varie fasi delle attività sono stati coinvolti, con ruoli diversi, tutti gli attori e i destinatari principali del progetto: ricercatori, studenti universitari dei Master “Didattica museale generale” e “Studi avanzati di educazione museale”, docenti di scuola primaria e secondaria di secondo grado, e, ovviamente, bambini e ragazzi delle scuole aderenti. In particolare, nel presente contributo vengono illustrate le attività svoltesi presso il Museo Nazionale Etrusco di Villa Giulia di Roma, con gli alunni dell’I.C. Mario Lodi, e presso il Museo Diocesano di Genova e in classe, con gli alunni dell’IC Santa Marta, volte alla creazione di infografiche in un contesto museale