Disturbo dell'Adattamento in ambito professionale: caratteristiche generali e aspetti psicopatologici dello stress occupazionale

La tesi si propone di valutare le caratteristiche del Disturbo dell’Adattamento nell’ambito professionale. Nella prima parte è descritto lo stress nei suoi aspetti storici, clinici e nelle sue conseguenze, in particolare la psicopatologia specifica da eventi stressanti. A questo quadro iniziale segue una descrizione dei rischi psicosociali quali lo stress occupazionale, il burnout e il fenomeno Mobbing. Nella seconda parte viene discusso lo studio effettuato. È stato esaminato un campione di 580 soggetti afferenti presso il Centro di disadattamento lavorativo della Medicina del Lavoro dell’AOUP e che hanno richiesto una valutazione in quanto ritengono di essere vittime di violenza psicologica sul luogo di lavoro. Da questo sono stati selezionati 275 soggetti suddivisi in due sottogruppi sulla base della Diagnosi di Disturbo di Adattamento (casi) e delle Diagnosi di Depressione Maggiore e/o Disturbo di Panico (controlli). Gli scopi sono stati quelli di definire se, in situazioni di stress lavorativo, coloro che presentano un disturbo reattivo agli eventi (DDA) hanno delle caratteristiche (demografiche, psicopatologiche, lavorative) che li distinguono rispetto a chi presenta altri disturbi di Asse I. Inoltre è stato valutato se esiste un profilo di personalità caratteristico in chi presenta un disturbo reattivo ad eventi rispetto a chi presenta altri disturbi di Asse I. Dalle analisi dei dati dello studio emerge che il Disturbo dell’Adattamento si caratterizza per la conservazione dell’autostima, l’assenza di rischio suicidario, mentre non si presentano differenze riguardo la vulnerabilità psicopatologica degli individui, indagata con la valutazione della presenza di una familiarità psichiatrica e con l’analisi dei profili di personalità. Un aspetto di rilievo è la differente correlazione nei due sottogruppi fra condizioni di stress lavorativo e spettro dell’umore. Nei soggetti con DDA un maggiore stress lavorativo si correla con una sintomatologia sottosoglia maniacale mentre nel sottogruppo Umore/Ansia con quella depressiva. Queste caratteristiche distintive depongono quindi per un’autonomia diagnostica del Disturbo dell’Adattamento e non per una forma quantitativamente minore degli specifici disturbi d’ansia e dell’umore, di cui non viene raggiunta la soglia diagnostica. Per quanto riguarda gli aspetti psicopatologici e i tratti di personalità non è possibile stabilire un rapporto lineare fra caratteristiche di personalità, vulnerabilità nei confronti delle situazioni ad alta intensità conflittuale e sviluppo di una sintomatologia, come conseguenza delle vessazioni in ambito lavorativo. Per far luce su questi aspetti può essere utile l’impiego di strumenti più sensibili per valutare la presenza di una familiarità psichiatrica e di situazioni stressanti nell’arco della vita (non solo in ambito lavorativo) nonché l’utilizzo di strumenti diagnostici per i disturbi di personalità, al fine di valutare più accuratamente la presenza di una maggiore vulnerabilità psicopatologica dei soggetti che sono sottoposti a stress occupazionale

EGFR inhibitor as second-line therapy in a patient with mutant RAS metastatic colorectal cancer: circulating tumor DNA to personalize treatment

A 47-year-old male patient presented in March 2016 to our unit with a palpable painless left supraclavicular mass. A whole-body contrastenhanced computed tomography (CT) scan revealed a left supraclavicular lymphadenopathy, transverse colon thickening (3 cm), multiple chest and abdominal lymphadenopathies, and peritoneal carcinomatosis. Colonoscopy revealed a bleeding area at 15 cm from the anal verge; biopsy was performed, and the result was negative for a primary cancer

Lamin A/C Mechanotransduction in Laminopathies

Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Although the exact mechanisms governing laminopathies and gene expression are still not clear, a strong correlation has been found between cell functionality and nuclear behavior. New theories base on the direct effect of external force on the genome, which is indeed sensitive to the force transduced by the nuclear lamina. Nuclear lamina performs two essential functions in mechanotransduction pathway modulating the nuclear stiffness and governing the chromatin remodeling. Indeed, A-type lamin mutation and deregulation has been found to affect the nuclear response, altering several downstream cellular processes such as mitosis, chromatin organization, DNA replication-transcription, and nuclear structural integrity. In this review, we summarize the recent findings on the molecular composition and architecture of the nuclear lamina, its role in healthy cells and disease regulation. We focus on A-type lamins since this protein family is the most involved in mechanotransduction and laminopathies

Leveraging Non-negative Matrix Tri-Factorization and Knowledge-Based Embeddings for Drug Repurposing: an Application to Parkinson's Disease

Drug repurposing, which involves using already approved drugs for new clinical targets, represents a cost-effective alternative to the development of new drugs. In this study, we introduce an innovative computational strategy, which uses Non-negative Matrix Tri-Factorization (NMTF) to generate vector embeddings of given sizes for drugs and drug targets; vector embeddings are then employed to generate predictions for drug repurposing using conventional classifiers, like random forest, logistic regression, and multi-layer perceptron. Our approach leverages the NMTF method within a new approach to classification, named two-tower architecture, which is effective in solving complex tasks, such as the optimal prediction of targets for already approved drugs. This approach produces robust models, with AUROC reaching 0.90, which outperform traditional NMTF. We evaluate our method in the context of Parkinson's Disease; within the newly revealed drug-target predictions, we highlight compounds that exhibit potential in mitigating neurodegeneration, thereby revealing a potentially useful drug in relationships with a well-identified target

Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression, an effect amplified by interleukin-1β

The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling. We investigated the role of endothelial Notch1 in this IL-1β-mediated process. Brief treatment with IL-1β upregulated endothelial VCAM1 and Notch ligand Jagged1. IL-1β decreased Notch1 mRNA levels, but levels of the active Notch1ICD protein remained constant. IL-1β-mediated VCAM1 induction was downregulated in endothelial cells subjected to pretreatment with a pharmacological inhibitor of the γ-secretase, which activates Notch receptors, producing NotchICD. It was also downregulated in cells in which Notch1 and/or Jagged1 were silenced.Conversely, the forced expression of Notch1ICD in naïve endothelial cells upregulated VCAM1 per se and amplified IL-1β-mediated VCAM1 induction. Jagged1 levels increased and Notch4 signaling was downregulated in parallel. Finally, Notch1ICD and Jagged1 expression was upregulated in the endothelium of the liver in a model of chronic liver inflammation.In conclusion, we describe here a cell-autonomous, pro-inflammatory endothelial Notch1-Jagged1 circuit (i) triggering the expression of VCAM1 even in the absence of inflammatory cytokines and (ii) enhancing the effects of IL-1β. Thus, IL-1β regulates Notch1 and Notch4 activity in opposite directions, consistent with a selective targeting of Notch1 in inflamed endothelium

Many-body kinetics of dynamic nuclear polarization by the cross effect

Dynamic nuclear polarization (DNP) is an out-of-equilibrium method for generating nonthermal spin polarization which provides large signal enhancements in modern diagnostic methods based on nuclear magnetic resonance. A particular instance is cross-effect DNP, which involves the interaction of two coupled electrons with the nuclear spin ensemble. Here we develop a theory for this important DNP mechanism and show that the nonequilibrium nuclear polarization buildup is effectively driven by three-body incoherent Markovian dissipative processes involving simultaneous state changes of two electrons and one nucleus. We identify different parameter regimes for effective polarization transfer and discuss under which conditions the polarization dynamics can be simulated by classical kinetic Monte Carlo methods. Our theoretical approach allows simulations of the polarization dynamics on an individual spin level for ensembles consisting of hundreds of nuclear spins. The insight obtained by these simulations can be used to find optimal experimental conditions for cross-effect DNP and to design tailored radical systems that provide optimal DNP efficiency

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05–0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76–5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11–0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25–1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49–0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05–0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76–5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11–0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25–1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49–0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results