Nel saggio si è cercato di evidenziare gli elementi di attrazione del convento agostiniano riformato di S. Maria del Popolo di Roma e i rapporti che i frati lombardi – di cui si sono messe in luce le ...personalità più eminenti che vi risiedettero – seppero intrecciare da una parte con gli ambienti ecclesiastici e curiali e dall’altra con le diverse realtà della società cittadina, che a vario titolo si trovarono a gravitare intorno ad esso e alla chiesa posta sotto la loro cura.
The de novo synthesis of piperidine nucleosides from our homologating agent 5,6-dihydro-1,4-dithiin is herein reported. The structure and conformation of nucleosides were conceived to faithfully ...resemble the well-known nucleoside drugs Immucillins H and A in their bioactive conformation. NMR analysis of the synthesized compounds confirmed that they adopt an iminosugar conformation bearing the nucleobases and the hydroxyl groups in the appropriate orientation.
The current study aims at examining the relationship between the perfectionism two-factor model (i.e., concerns and strivings) and burnout dimensions measured by using the BAT (Burnout Assessment ...Tool) through a longitudinal study. A two-wave cross-lagged study was conducted using path analysis in SEM (Structural Equation Modeling) of 191 workers. Results confirmed the predictive role of perfectionistic concerns on the burnout dimensions, whereas perfectionistic strivings were not significantly related, suggesting that perfectionism should be monitored by employers and clinicians to prevent employee burnout. Limitations and future research directions are envisaged.
Iminosugars are sugar analogues endowed with a high pharmacological potential. The wide range of biological activities exhibited by these glycomimetics associated with their excellent drug profile ...make them attractive therapeutic candidates for several medical interventions. The ability of iminosugars to act as inhibitors or enhancers of carbohydrate-processing enzymes suggests their potential use as therapeutics for the treatment of cystic fibrosis (CF). Herein we review the most relevant advances in the field, paying attention to both the chemical synthesis of the iminosugars and their biological evaluations, resulting from in vitro and in vivo assays. Starting from the example of the marketed drug NBDNJ (
-butyl deoxynojirimycin), a variety of iminosugars have exhibited the capacity to rescue the trafficking of F508del-CFTR (deletion of F508 residue in the CF transmembrane conductance regulator), either alone or in combination with other correctors. Interesting results have also been obtained when iminosugars were considered as anti-inflammatory agents in CF lung disease. The data herein reported demonstrate that iminosugars hold considerable potential to be applied for both therapeutic purposes.
The present paper, in the framework of a search for a computer-aided method to detect depression, deals with experimental data of various types, with their correlation, and with the way relevant ...information about depression delivered by different sets of data can be fused to build a unique body of knowledge about individuals’ mental states facilitating the diagnosis and its accuracy. To this aim, it suggests the use of a recently introduced «limiting form» of the kinetic-theoretic language, at present widely used to describe complex systems of objects of the most diverse nature. In this connection, the paper mainly aims to show how a wide range of experimental procedures can be described as examples of this «limiting case» and possibly rendered by this description more effective as methods of prediction from experience. In particular, the paper contains a simple, preliminary application of the method to the detection of depression, to show how the consideration of statistical parameters connected with the analysis of speech can modify, at least in a stochastic sense, each diagnosis of depression delivered by the Beck Depression Inventory (BDI-II).
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease ...(GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues. Since the impairment of MSC functions could pose profound consequences on body physiology, we evaluated whether GBA and GLA silencing could affect the biology of MSCs isolated from bone marrow and amniotic fluid. Those cell populations were chosen given the former's key role in organ physiology and the latter's intriguing potential as an alternative stem cell model for human genetic disease. Our results revealed that GBA and GLA deficiencies prompted cell cycle arrest along with the impairment of autophagic flux and an increase of apoptotic and senescent cell percentages. Moreover, an increase in ataxia–telangiectasia‐mutated staining 1 hr after oxidative stress induction and a return to basal level at 48 hr, along with persistent gamma‐H2AX staining, indicated that MSCs properly activated DNA repair signaling, though some damages remained unrepaired. Our data therefore suggest that MSCs with reduced GBA or GLA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity.
Gaucher disease (GD) and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha‐galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected; thus, we evaluated whether GBA and GLA silencing could affect the biology of mesenchymal stem cells (MSCs) isolated from bone marrow and amniotic fluid. Our data suggest that MSCs with reduced GBA or GLA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity.
In this research, we analyse data obtained from sensors when a user handwrites or draws on a tablet to detect whether the user is in a specific mood state. First, we calculated the features based on ...the temporal, kinematic, statistical, spectral and cepstral domains for the tablet pressure, the horizontal and vertical pen displacements and the azimuth of the pen's position. Next, we selected features using a principal component analysis (PCA) pipeline, followed by modified fast correlation-based filtering (mFCBF). PCA was used to calculate the orthogonal transformation of the features, and mFCBF was used to select the best PCA features. The EMOTHAW database was used for depression, anxiety and stress scale (DASS) assessment. The process involved the augmentation of the training data by first augmenting the mood states such that all the data were the same size. Then, 80% of the training data was randomly selected, and a small random Gaussian noise was added to the extracted features. Automated machine learning was employed to train and test more than ten plain and ensembled classifiers. For all three moods, we obtained 100% accuracy results when detecting two possible grades of mood severities using this architecture. The results obtained were superior to the results obtained by using state-of-the-art methods, which enabled us to define the three mood states and provide precise information to the clinical psychologist. The accuracy results obtained when detecting these three possible mood states using this architecture were 82.5%, 72.8% and 74.56% for depression, anxiety and stress, respectively.