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Echocardiographic Assessment of Right Ventricular–Pulmonary Arterial Coupling in Heart Failure: Prognostic Insights from a Systematic Review
No full textBackground: Prognostic heterogeneity in heart failure (HF) is substantial and not fully
captured by conventional left-sided echocardiographic parameters. Growing evidence
highlights the importance of right ventricular–pulmonary arterial (RV–PA) interaction in
HF pathophysiology and outcomes. The echocardiographic tricuspid annular plane systolic
excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio has been proposed
as a simple noninvasive surrogate of RV–PA coupling, yet its prognostic value across the
HF spectrum remains incompletely defined. Methods: This systematic review followed
PRISMA guidelines and was registered in INPLASY. PubMed, Scopus, and EMBASE were
searched from inception through January 2026 for observational studies evaluating the
prognostic value of TAPSE/sPAP in adult patients with HF. Study selection, data extraction,
and risk-of-bias assessment were performed independently by two reviewers. Owing to
substantial heterogeneity, a qualitative synthesis with weighted pooled descriptive statis-
tics was performed. Results: Fifteen observational studies including 5389 patients were
analyzed, with a median follow-up of approximately 1.9 years, ranging from in-hospital
outcomes to long-term follow-up of up to 15 years. Study populations encompassed a wide
range of HF phenotypes and clinical settings, including acute and chronic HF, preserved
and reduced ejection fraction, valvular heart disease, infiltrative cardiomyopathies, and
advanced HF. Across studies, reduced TAPSE/sPAP was generally associated with adverse
outcomes, including all-cause mortality and HF-related events, with reported hazard ratios
ranging from approximately two- to five-fold. Prognostically relevant TAPSE/sPAP cut-off
values tended to cluster within a relatively narrow range, with most thresholds between
0.36 and 0.40 and a weighted median of approximately 0.36. When reported, TAPSE/sPAP
showed favorable discriminative performance for adverse outcomes. Overall methodologi-
cal quality was predominantly fair. Conclusions: Across heterogeneous HF populations,
impaired TAPSE/sPAP appears to be a consistent marker of adverse prognosis. These
findings support TAPSE/sPAP as a practical, noninvasive indicator of RV–PA uncoupling
that may contribute to risk stratification and phenotyping in heart failure. Prospective
studies focusing on specific HF phenotypes are needed to clarify its role in longitudinal
monitoring and therapeutic decision-making
IL CANONE DELLA RIDUCIBILITÀ ALLA PROVA DEI FATTI: CRITICITÀ PERSISTENTI NEL MECCANISMO DI LEGITTIMAZIONE DELLA PENA PERPETUA
No full textThe dissertation examines the compatibility of life imprisonment with the constitutional and conventional principles governing the function of punishment in the Italian legal system, focusing in particular on the principle of reducibility as a structural condition for the legitimacy of life sentences. Starting from an analysis of the normative framework and the constitutional foundations of punishment, the work traces the emergence of reducibility as an essential criterion to prevent life imprisonment from degenerating into mere incapacitation. The core of the study lies in assessing the actual effectiveness of parole (liberazione condizionale) through an examination of statistical data concerning its application to life-sentenced prisoners, which highlights a significant divergence between the formal legal structure and its concrete implementation. This discrepancy risks emptying the rehabilitative function of its substantive meaning, turning life imprisonment into a sentence devoid of any real prospect of release. The analysis then turns to “ergastolo ostativo”, showing how, despite the reform introduced by Law no. 199/2022, reducibility remains, in practice, a residual and conditional outcome. The thesis argues that a reform of the parole mechanism is necessary, introducing periodic and substantive judicial assessments of the prisoner’s personal transformation, in order to restore coherence between the constitutional model of punishment and the actual dynamics of its execution
The effectiveness of high-intensity interval training (HIIT) in adults with psychiatric disorders: a scoping review
No full textBackground Psychiatric disorders are associated with significant disability, and patients sometimes respond partially to conventional therapies. Objectives Purpose of the present manuscript is to summarize the available literature on the effectiveness of high-intensity interval training (HIIT) in patients affected by mental conditions. The primary research question is whether HIIT can improve the symptoms of various psychiatric conditions, possibly in augmentation to standard therapies. Methods The review was conducted following the PRISMA guidelines adapted for scoping reviews. A bibliographic search was conducted on the following database sources: Pubmed, Embase and Scopus. English-language publications about HIIT intervention in adult patients with mental disorders were reviewed. Fourteen studies met the inclusion criteria and were finally included in this review. Results HIIT contributes to reduce the global severity of illness of several psychiatric conditions, with an effectiveness at least comparable to other non-pharmacological approaches (effect size d range: 0.36-2.10). Most studies regard patients affected by schizophrenia or depressive disorders. Conclusions HIIT may be considered a complementary option to improve symptoms of several psychiatric conditions. More studies are needed to identify the best patient profile for this protocol
La posizione ordinamentale della magistratura contabile rispetto a quella amministrativa, alla luce della recente riforma
No full textAttraverso l’intervento si cercherà di offrire una riflessione sul ruolo della
magistratura amministrativa nel sistema politico-istituzionale, concentrandosi sul
giudice amministrativo, precipuamente sul piano dell’organizzazione e sulle
implicazioni del suo operato sul controllo del potere pubblico.
Al centro dell’analisi vi sono i limiti del sindacato giurisdizionale sulle
scelte discrezionali dell’amministrazione, il delicato equilibrio tra tutela
giurisdizionale effettiva e autonomia dell’azione amministrativa, e la posizione
delle magistrature ‘speciali’ rispetto agli altri poteri dello Stato.
Il contributo andrà a confrontare la posizione ordinamentale della
magistratura amministrativa rispetto alla magistratura contabile. In particolare, per
quanto concerne la seconda, si presterà attenzione alle innovazioni introdotte dalla
legge n. 1 del 2026, la quale ha delegato il Governo a ridefinire l’organizzazione e
le funzioni della Corte dei conti. Tra le novità principali, a fini esemplificativi,
figurano l’integrazione delle funzioni consultive, di controllo e giurisdizionali, il
rafforzamento degli effetti nomofilattici delle Sezioni riunite, il potenziamento del
coordinamento della Procura generale e nuovi strumenti per assicurare uniformità
ed efficacia dell’azione requirente.
I citati cambiamenti offrono spunti per riflettere sulle conseguenze
organizzative della concentrazione delle competenze, sulla gestione dei carichi di
lavoro e sulla rotazione tra funzioni.
Si presterà particolare attenzione al ruolo del pubblico ministero contabile,
quale ruolo peculiare, che permette di riflettere – anche in chiave comparata – su
quanto tale ruolo possa influire sull’esercizio dello ius dicere da parte dei giudici
contabili.
Il confronto tra i due ordini di magistrature evidenzia sia questioni comuni,
quali la gestione di funzioni eterogenee, le tensioni tra legalità e discrezionalità, la
responsabilità, sia differenze organizzative e procedurali significative.
In conclusione, si offriranno alcune riflessioni sulla possibilità di
individuare categorie interpretative condivise per le magistrature ‘speciali’ e sui
limiti sistematici di tale approccio, nel contesto delle riforme recenti della Corte dei
conti, contribuendo al dibattito più ampio sulle trasformazioni del controllo
giurisdizionale e istituzionale sull’amministrazione
Biophysical Signatures of IGLV1-44 Light Chains in AL, POEMS, and MM: Uncovering Pathogenic Determinants
No full textOverexpression of immunoglobulin light chains (LCs) is observed in various diseases, including
Multiple Myeloma (MM), Light Chain Amyloidosis (AL), and POEMS syndrome. LCs play
different pathological roles across these conditions, leading to distinct clinical manifestations.
In AL, circulating LCs may either aggregate and deposit as amyloid fibrils in various organs or
cause cardiotoxicity in their soluble form [1,2]. In contrast, POEMS syndrome is characterized
by poorly understood toxic effects of LCs, even in the absence of fibril formation [3]. In MM,
however, LCs do not exhibit toxic effects despite their abundant presence in circulation. Due to
genetic rearrangement and somatic hypermutation, each patient expresses unique LC sequences.
Nonetheless, certain germline genes are more frequently represented. Notably, the IGLV1-44
gene is commonly observed in patients with MM, AL, and POEMS, encoding LCs that, despite
sharing high structural similarity and approximately 85% sequence conservation, display
different pathological behaviors and associated clinical outcomes. To date, the specific
sequence patterns responsible for LC pathogenicity remain unidentified, hindering the
establishment of a reliable sequence–disease correlation [4,5]. Such a correlation would be
valuable for early diagnosis and the development of potential LC-targeting therapies. In this
context, this project aims to perform a comprehensive biophysical analysis of a large set of
IGLV1-44 LCs derived from AL and POEMS patients, to identify characteristic biophysical
features within each group. In parallel, four non-toxic IGLV1-44 LCs from MM patients will be
analyzed as a reference for comparison with toxic LCs. To this end, LCs from AL, POEMS, and
MM patients have been recombinantly purified and biophysically characterized to assess and
compare their thermodynamic and kinetic stability, flexibility, and susceptibility to proteolysis.
Overall, this study will support the correlation of specific IGLV1-44 germline mutations with
LC overproduction-related diseases, offering new perspectives for diagnosis and therapeutic
development
Commentario tematico del Regolamento (UE) 2024/1689 e della legge italiana 23 settembre 2025, n. 132
No full textIl Commentario tematico nasce con l’obiettivo di fornire agli studiosi, ai professionisti e agli operatori istituzionali uno strumento di lettura sistematica delle risposte normative – europea e nazionale – all’intelligenza artificiale, capace di coniugare rigore teorico, attenzione ai diritti fondamentali e sensibilità per le ricadute applicative delle nuove tecnologie. Il volume raccoglie i contributi di giuristi e giuriste dell’Università degli Studi di Milano e dell’Universidad de Granada, con riferimento alle previsioni del Regolamento UE 1689/24 e della legge italiana, n. 132/2025, valorizzandone snodi problematici e profili di coordinamento
Fitting a Square Peg in a Round Hole? : Challenges and Prospects of Inter-State Human Rights Complaints as (Overlapping) Avenues for Individual Reparations
No full textThis article examines the evolving role of inter-state human rights complaints as a procedural avenue for reparations, particularly where they intersect with individual claims. Traditionally regarded as diplomatic instruments or tools of strategic litigation, inter-state applications increasingly serve as mechanisms for addressing large-scale human rights violations. This study analyses the legal framework governing such proceedings and examines whether and to what extent human rights bodies reconcile State responsibility with individual reparations. It further investigates the complexities of quantifying and allocating reparations in overlapping claims, particularly concerning res judicata, lis pendens, and the prohibition of double recovery. Additionally, it evaluates the potential of friendly settlements as a flexible mechanism for balancing sovereign interests with victims’ rights. Ultimately, the article advocates for a cohesive and integrated framework that harmonizes judicial adjudication with alternative reparative mechanisms, reinforcing accountability and strengthening human rights protection in inter-state litigation
Z-boson quantum tomography at next-to-leading order
No full textWe investigate the origin of the unusually large electroweak (EW) radiative effects
observed in the extraction of the spin-density matrix and related observables at colliders,
focusing on leptonic Z-boson decays. We compute the Z-boson decay spin-density matrix at
next-to-leading order (NLO) and find that, while its analytic structure remains essentially
unchanged with respect to leading order, the EW corrections induce a sizeable −35% shift
in the spin-analysing power parameter ηl. This effect alone accounts for the striking size
of the corrections. For boosted Z bosons, we further show that the treatment of photon
radiation in lepton-dressing algorithms significantly affects the extraction of spin-density-
matrix coefficients at NLO and must be carefully controlled. To address these challenges, we
propose a quantum tomography procedure that is applicable to any final state with one or
more on-shell Z bosons that is robust under higher-order corrections. We illustrate its validity
and limitations in pp → ZZ → 4l and in heavy (MH > 2MZ) Higgs boson decay H → ZZ → 4l
DpaA and Lpp affect LD-cross-link formation in Escherichia coli
No full textPeptidoglycan (PG) is an essential component of the cell envelope, required to mechanically sustain the turgor pressure of the cytoplasm. In Escherichia coli, the PG consists of glycan chains with attached stem peptides mainly cross-linked via DD-cross-links formed between Alanine (D-Ala4) and meso-diaminopimelic acid (DAP3) by DD transpeptidases (Vollmer et al., 2008). A small amount of LD-cross-links occurs between two DAP3 residues, formed by LD-transpeptidases members of the YkuD family of proteins (Magnet et al., 2008). Although not essential under standard laboratory conditions, LD-cross-links become crucial for β-lactam resistance, PG homeostasis and survival under stress conditions (Hugonnet et al., 2016, Morè et al., 2019, Alvarez et al., 2024). E. coli has two LD transpeptidases, LdtD and LdtE for LD-cross-link formation (Magnet et al., 2008). LdtD is the cell envelope-stress-induced LDT and LdtE is the housekeeping LDT active under non-stress conditions (Morè et al., 2019). Interestingly, the formation of LD-cross-links by LdtE requires DpaA, another YkuD protein family member, which detaches the outer membrane (OM)-anchored lipoprotein Lpp from the PG (Badour et al., 2021; Winkle et al., 2021). Lpp (Braun lipoprotein) is the most abundant OM lipoprotein which is attached to PG via its terminal Lys and a DAP3 residue in the PG. This is the only covalent linkage between the PG and OM and is needed to maintain a robust cell envelope. By analysing the PG composition of wild type and mutants lacking ldt genes, dpaA, and/or lpp, we found that DpaA and Lpp are both required for LD-cross-link formation by LdtE, highlighting the unexpected functional interaction between Lpp detachment dynamics and LD-cross-link formation