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Establishing Triple Chronotherapy as a fast-acting add-on treatment for unipolar and bipolar depression: evidence from an open-label randomized controlled trial in a real-world inpatient setting
No full textBackground Despite established treatments like cognitive-behavioral therapy and antidepressants, response rates remain suboptimal during depressive episodes, with delayed onset of action. Circadian rhythm disturbances are closely linked to mood disorders, and chronotherapeutic interventions, including Sleep Deprivation, Sleep Phase Advance, and Bright Light Therapy, have shown promise in rapidly alleviating depressive symptoms, though post-treatment relapse risks are notable. Methods This Randomized Controlled Trial (EUPAS30637) evaluates Triple Chronotherapy (TCT) as an adjunctive treatment for Major Depressive Episodes (MDEs) in a real-world hospital setting, comparing it to Treatment-As-Usual (TAU). The primary outcome was the longitudinal trajectory of Hamilton Depression Rating Scale (HDRS) scores assessed at several other timepoints. Secondary outcomes included changes in depressive symptoms at these timepoints, reductions in suicidality, length of hospitalization, and readmissions within three months post-discharge. Results Twenty-four patients were enrolled in the TCT and 20 in the TAU groups. Only one TCT participant withdrew because they could not tolerate sleep deprivation. At baseline, groups showed similar demographics and symptom severity. Compared with TAU, add-on TCT produced greater and more rapid reductions in depression scores by day 5 that persisted through day 12 and at discharge. Suicidality also decreased to a greater extent in the TCT group. Length of stay was shorter with TCT, but readmission rates did not differ significantly in the long term. Discussion These findings suggest that add-on TCT can rapidly reduce depressive symptoms and improve associated outcomes in hospitalized patients with moderate MDEs. Future research with larger samples and longer follow-ups should further explore TCT's efficacy and safety, aiming to optimize treatment strategies for depressive episodes
Modeling Mowat-Wilson syndrome with patient iPSCs reveals transcriptional and phenotypic defects in neural progenitors
No full textZinc finger E-box-binding homeobox 2 (ZEB2) is a key transcription factor involved in multiple aspects of nervous system development, including neuronal specification, migration, and differentiation. Loss-of-function variants in ZEB2 cause Mowat-Wilson syndrome (MWS), a severe neurodevelopmental disorder characterized by intellectual disability, epilepsy, and brain structural abnormalities. In this study, we generated and characterized induced pluripotent stem cell (iPSC) lines from MWS patients carrying pathogenic ZEB2 variants. Patient-derived iPSCs retained full pluripotency and were capable of differentiating into all three germ layers, including neural lineages. Upon directed differentiation into neural progenitor cells (NPCs) and early neurons, we identified distinctive transcriptional alterations affecting neuroepithelial-to-radial glia transition and lineage specification. RNA-seq analysis revealed dysregulation of genes involved in cytoskeletal remodeling, extracellular matrix organization, and cell motility. Functional holographic live imaging confirmed a significant increase in motility behavior in MWS NPCs and early neurons, suggesting that altered cell dynamics may underlie aberrant neural circuit formation. Despite these changes, early neuronal markers such as MAP2 were expressed at comparable levels in MWS and control cells. Together, these findings uncover novel cellular and molecular phenotypes associated with ZEB2 deficiency and provide insight into how disrupted progenitor behavior and transcriptional mis-regulation may contribute to the neurodevelopmental features of MWS
O direito sindical no sistema jurídico italiano e brasileiro
No full textIl confronto tra diversi modelli nazionali di regolazione dei rapporti collettivi di lavoro costituisce un’operazione di indubbio interesse sul piano comparatistico soprattutto ove tra i sistemi dedotti in comparazione sussista un preciso rapporto di derivazione storica. Attraverso l’approfondita analisi dei diversi aspetti del diritto sindacale i volumi intendono dare conto delle profonde differenze che intercorrono tra la disciplina italiana che, una volta caduto l’ordinamento corporativo, ha adottato un modello di regolazione stabilmente improntato alla libertà sindacale, e l’ordinamento brasiliano, il quale, al contrario, si contraddistingue tuttora per una disciplina largamente ispirata proprio al modello corporativo italiano. La pubblicazione del volume in duplice versione italiana e portoghese mira ad agevolare, in coerenza con la finalità della Collana, il confronto e il dibattito tra gli studiosi di entrambi i Paesi
Apathy and Depression Impact on Cognitive Decline: Neuropsychological Specificities across Neurodegenerative Diseases
No full textObjective Apathy is a common symptom across neurodegenerative diseases with origins still debated. “Vascular apathy hypothesis” by Van der Mast suggests vascular pathologies precede apathy. Other evidence points to dysfunction in dopamine pathways, driving apathy by impairing goal-directed behaviour. The impact of apathy on cognitive decline and autonomy, particularly with coexisting depression, remains unclear. This cross-sectional study aimed to (1) characterize apathy in vascular dementia, Parkinson’s disease (PD), and Mild Cognitive Impairment-Alzheimer Disease (MCI-AD) regarding incidence, severity, and cognitive specificity; (2) differentiate effects of apathy and depression on cognitive impairment and daily autonomy (Activities of Daily Living [ADL]). Method Fifty-three patients underwent neuropsychological testing and completed the Geriatric Depression Scale, Starkstein’s Apathy Scale, and ADL questionnaire at a clinical neuropsychology outpatient setting in Milan. Results 56% patients had cardiovascular pathologies, 20% had PD, and 22% had MCI-AD. Neither prevalence nor severity of apathy or depression differed significantly across diseases. Hierarchical regression showed apathy predicted language initiative controlling for depression (R2=0.249; F(2)=4.144; p=.028), and inversely correlated with working memory, language and frontal functioning, while depression predicted autonomy controlling for apathy (R2=0.234; F (2)=3.821; p=.036). Conclusions Apathy is prevalent across different neurodegenerative diseases and exacerbates specific cognitive impairments. Distinguishing vascular apathy from other forms remains challenging
LE RAGIONI DI UNA RINUNCIA: IGOR MARKEVITCH COMPOSITORE DA PARIGI ALL¿ITALIA DELLA RESISTENZA
No full textThe dissertation investigates the figure of Igor Markevitch, from his early years as a composer in Paris in the late 1920s, to the period of World War II, when he completely abandoned composition in favor of a full dedication to orchestral conducting. The objective of the research is to shed light on the causes of this "moult," retracing the artistic and personal trajectory of the musician within his historical and social context
Le autorità nazionali per l'IA tra vigilanza, coordinamento e sviluppo : Commento all’art. 20
No full textUnravelling the function of chromatin remodellers in response to environmental stress
No full textLight is an essential cue for plants, effectively regulating multiple molecular and
physiological mechanisms (Li et al., 2021). Phytochrome B (PhyB) is the photoreceptor
specialised in perceiving high red:far red-light ratio, which in turn also activates PhyB and
allows its translocation to the nucleus (Kim et al., 2023). In the nucleus, upon light, PhyB
notably interacts with PHYTOCHROME INTERACTING FACTOR 4 (PIF4), a transcription
factor involved in hypocotyl elongation, triggering its degradation and allowing the process
known as photomorphogenesis (Pham et al., 2017). Epigenetic marks and chromatin
regulation are deeply tied with transcriptional regulation, playing a fundamental role in
environmental cues perception. Among those, histone deacetylase complexes formed by
catalytic subunits Histone Deacetylase 6 (HDA6) and HDA19 are known to participate to
abiotic stress perception and photoperiodic flowering (Ning et al., 2019; Chen et al., 2010).
Interestingly, both complexes share a non-catalytic subunit known as HISTONE
DEACETYLASE COMPLEX 1 (HDC1), which mimics their deacetylating function in these
processes (Perrella et al., 2024). Here, we aim to explore the involvement of HDC1 in
photomorphogenesis and its interplay with downstream light signalling components. Our
findings suggest that HDC1 is a negative regulator of photomorphogenesis that primarily
responds to red light (Fang et al., 2025). HDC1 does not only act through deacetylation,
but it also directly interacts with PIF4 and promotes its accumulation. Moreover, ChIP
analyses reveal that HDC1-mediated deacetylation is a requisite for PIF4 binding to its
targets. ATAC-seq experiments show that HDC1 is not determinant for chromatin
accessibility, while loss of PIF4 greatly affects its dynamics. Meta-analysis of publicly
available datasets suggest that PIF4-dependent DNA accessibility may be required for the
recruitment of the bZIP transcription factor ABRE-binding factor 3 (ABF3), thus revealing a
novel interplay between chromatin remodelling and transcription in plants
Il divieto di categorizzazione biometrica sulla base della vita sessuale e dell'orientamento sessuale : Commento all’art. 5, par. 1, lett. g)
No full textTranslating Syrian Politics: Teaching Activities Based on Dima Wannous’s Writings
No full textContemporary Syrian literature is an interesting case study for both the translation of political discourse and the politics of translation. Many literary works describe the political context of the past decades, and some of them also cover the scenario after the 2011 uprisings. In terms of global circulation, some recent novels and memoirs have been translated into several languages and are read as an account from within, sometimes overlooking their aesthetic features.
This chapter investigates the possibility of teaching the language of Syrian politics through the analysis and translation of the novel al-Khāʾifūn (2017; The Frightened Ones 2021) by Dima Wannous (Dīma Wannūs, b. 1982). This novel stages two conflicting political discourses: official slogans circulating in public spaces, such as schools and television, and the language of the demonstrations that breaks imposed silence. This battle over words reflects the resurgence of some identity-related divisions fuelled by sectarianism. These three axes of political discourse (slogans, oppositional discourse vs. imposed silence, and battle over words) are examined by looking at the character’s interiorization of politics, their lexical choices, and linguistic variation with a focus on the Alawite accent. Each topic is accompanied by a translation activity to train the students in searching secondary sources to understand the political references, foster debate on the relation between language and ideology, and experience translation as a creative process
Robotics vs. laparoscopy in spleen-preserving distal pancreatectomy in the IGOMIPS registry: when glitter does not equal superiority
No full textSpleen-preserving distal pancreatectomy (SPDP) reduces the risks associated with splenectomy and can be performed laparoscopically (Lap-SPDP) or robotically (Rob-SPDP). Whether robotic assistance improves spleen preservation compared with laparoscopy remains unclear. A retrospective cohort study was conducted using the prospective Italian Registry of Minimally Invasive Pancreatic Surgery (IGOMIPS). All consecutive patients scheduled for SPDP between September 2019 and July 2024 were analyzed according to an intention-to-treat protocol. Primary endpoint was intraoperative deviation from planned SPDP; secondary endpoints included intra- and postoperative outcomes. Propensity score matching was performed to adjust for baseline variables, with a second propensity score matching including center volume and surgeon experience. Of 3045 procedures, 270 were planned SPDP (Rob-SPDP n = 138, Lap-SPDP n = 132). Overall intraoperative deviation occurred in 22.6% of cases, most commonly conversion to distal pancreatectomy with splenectomy. Spleen-vessel preservation rates were similar for Rob-SPDP (87.9) and Lap-SPDP (90.6%; p = 0.5561). Robotic procedures had longer operative time but lower stapler use. No significant differences were observed in severe complications, mortality, length of stay, or other postoperative outcomes in unmatched or matched cohorts. Robotic use increased significantly over time and was predominant in centers with robotic platforms and higher volumes. In a prospective national registry, Lap-SPDP and Rob-SPDP achieved comparable spleen preservation rates and perioperative outcomes. Robotic assistance did not confer measurable clinical advantages, though its adoption is increasing, particularly in high-volume, well-equipped centers