Search

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis. Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria. Methods: The patient was referred to neurological and neuropsychological examination. She underwent 3 Tesla magnetic resonance imaging (MRI) and genetic studies. Results: The neuropsychological examination revealed profound deficits in all cognitive domains and 3T brain MRI showed marked fronto-temporal atrophy. A mutation in the GRN gene further confirmed the diagnosis. Conclusions: The present case documents an unusual onset of bvFTD and highlights the problematic nature of the differential diagnosis between prodromal psychiatric features of the disease and primary psychiatric disorders. Early recognition and diagnosis of bvFTD can lead to appropriate management and support for patients and their families. This case highlights the importance of considering neurodegenerative diseases, such as bvFTD, in the differential diagnosis of psychiatric disorders, especially when exacerbations of behavioral traits manifest in adults. [ABSTRACT FROM AUTHOR]

Background and Aims Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. Methods Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. Results Data for 840 consecutive patients treated in 2014–2021 at a median age of 29.2 (19.0–41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%–99.2%] of patients. Median follow-up was 20.3 (7.1–38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P =.009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%–1.0%), 0.9% (0.2%–1.6%), and 3.8% (0.0%–8.4%); pulmonary valve replacement, 0.4% (0.0%–0.8%), 1.3% (0.2%–2.4%), and 8.0% (1.2%–14.8%); and pulmonary valve thrombosis, 0.4% (0.0%–0.9%), 0.7% (0.0%–1.3%), and 0.7% (0.0%–1.3%), respectively. Conclusions Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs. [ABSTRACT FROM AUTHOR]

Since SARS-CoV-2 emerged in 2019, strict monitoring of post-COVID-19 patients in order to ensure the early detection of sequelae and/or chronic organ damage that could been associated with the infection has been essential. Potential involvement of the NO pathway in the development of post-COVID-19 lung fibrotic alterations is feasible, since the majority of respiratory cells can produce NO, and fractional exhaled NO (FeNO) represents a biomarker of airway inflammation. The aim of this study was to investigate the potential utility of multiple-flow FeNO parameters in a post-COVID-19 population and to compare it with other indicators of lung damage proposed in the literature. We enrolled 20 patients hospitalized for COVID-19, who underwent clinical, respiratory functional (including PFTs and FeNO) and radiological follow-up after discharge. Compared with age- and sex-matched healthy controls, post-COVID-19 patients showed significantly higher FeNO 350 mL/s and CaNO levels. Moreover, among the parameters included in the follow-up, CaNO showed the best accuracy in indicating predominant fibrotic changes and GGO at CT scan. To our knowledge, this preliminary study has investigated for the first time multiple-flow FeNO parameters in a post-COVID-19 population. The evidence of increased CaNO values may imply the persistence of alveolar and bronchiolar inflammation and/or a mild impairment of the alveolar-capillary membrane in these patients.

Abstract The horizon quantum mechanics is an approach that was previously introduced in order to analyze the gravitational radius of spherically symmetric systems and compute the probability that a given quantum state is a black hole. In this work, we first extend the formalism to general space-times with asymptotic (ADM) mass and angular momentum. We then apply the extended horizon quantum mechanics to a harmonic model of rotating corpuscular black holes. We find that simple configurations of this model naturally suppress the appearance of the inner horizon and seem to disfavor extremal (macroscopic) geometries.

Mesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvironment. Recently, the role of extracellular vesicles (EVs) in mediating the therapeutic effects of MSCs has been recognized. Nevertheless, the molecular mechanisms responsible for the immunomodulatory properties of MSC-derived EVs (MSC-EVs) are still poorly characterized. Therefore, we carried out a molecular characterization of MSC-EV content by high-throughput approaches. We analyzed miRNA and protein expression profile in cellular and vesicular compartments both in normal and inflammatory conditions. We found several proteins and miRNAs involved in immunological processes, such as MOES, LG3BP, PTX3, and S10A6 proteins, miR-155-5p, and miR-497-5p. Different in silico approaches were also performed to correlate miRNA and protein expression profile and then to evaluate the putative molecules or pathways involved in immunoregulatory properties mediated by MSC-EVs. PI3K-AKT signaling pathway and the regulation of actin cytoskeleton were identified and functionally validated in vitro as key mediators of MSC/B cell communication mediated by MSC-EVs. In conclusion, we identified different molecules and pathways responsible for immunoregulatory properties mediated by MSC-EVs, thus identifying novel therapeutic targets as safer and more useful alternatives to cell or EV-based therapeutic approaches.

Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage.