Archivio istituzionale della Ricerca - Università degli Studi di Parma
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Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI)
No full textBackground: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment. Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR. Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement. Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment. Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714)
The role of organic acid counterions in modulating the in-vitro dissolution and permeability profiles of procaine salts
No full textProcaine, a widely used local anesthetic, suffers from slow onset and rapid degradation into para-aminobenzoic acid and diethylaminoethanol, resulting in a brief half-life and short duration of action. In this study, we investigate salification in order to modify dissolution rate and permeability without altering the chemical structure or using complex formulations. Six procaine salts with carboxylic acids and four with sulfonic acids were prepared and systematically evaluated in comparison with procaine hydrochloride, focusing on their in-vitro pharmacokinetic properties in two physiological conditions at pH 4.5 and 7.4. Dissolution rate studies showed that all procaine salts achieved complete dissolution within 30 min, while procaine reached 75 % dissolution and remained partially undissolved even after 2 h. In addition, permeability studies revealed a range of permeation values among the different procaine salts, in which sulfonate anions significantly improved the permeability of procaine by approximately 40 % to 70 %. Furthermore, a correlation between permeability and lipophilicity descriptors was assessed, with particular attention to ion pair stability, the lipophilicity of the counterion and the lipophilicity of procaine in its neutral form. Notably, salts with higher permeability, primarily sulfonates, exhibited less stable ion pairs, contributing to a more effective drug diffusion and a potential for faster onset and absorption of procaine. On the other side, carboxylic acids tend to confer a higher ion pair stability, inhibiting the membrane permeation. Our findings support the canonical model of passive permeability, suggesting that the neutral form of the drug can form in response to local environmental conditions near the membrane or within the transmembrane compartment. In this context, both the neutral form and the ion pair could contribute and play a role as a part of the equilibrium of partitioning across the membrane
FEM-Assisted Design and Characterization of a New Lithium Battery Pack-Heatsink Assembly
No full textThis work focuses on the design - driven by thermal simulations based on the finite element method (FEM) - and characterization of an assembly for temperature regulation of lithium battery packs. In this study we aim at developing a solution to achieve uniform temperature control over the cells of the battery pack. To this end, we included an aluminum plate featuring pins that thermally connect the battery pack to heat exchangers. To set the desired cell temperature, we considered thermal management systems with either air- or liquid-cooled heatsinks. Our findings indicate that a traditional serpentine liquid heatsink is particularly effective. Within the module, the heat transfer relies mainly on the aluminum plate and pins, which are designed to minimize the thermal resistance towards the heatsinks and to provide large thermal capacitance. This paper shows the main details of the FEM model, together with some validation results obtained using a dedicated test bench
Artificial intelligence in resuscitation: a scoping review
No full textBackground: Artificial intelligence (AI) is increasingly applied in medicine, with growing interest in its potential to improve outcomes in cardiac arrest (CA). However, the scope and characteristics of current AI applications in resuscitation remain unclear. Methods: This scoping review aims to map the existing literature on AI applications in CA and resuscitation and identify research gaps for further investigation. PRISMA-ScR framework and ILCOR guidelines were followed. A systematic literature search across PubMed, EMBASE, and Cochrane identified AI applications in resuscitation. Articles were screened and classified by AI methodology, study design, outcomes, and implementation settings. AI-assisted data extraction was manually validated for accuracy. Results: Out of 4046 records, 197 studies met inclusion criteria. Most were retrospective (90%), with only 16 prospective studies and 2 randomised controlled trials. AI was predominantly applied in prediction of CA, rhythm classification, and post-resuscitation outcome prognostication. Machine learning was the most commonly used method (50% of studies), followed by deep learning and, less frequently, natural language processing. Reported performance was generally high, with AUROC values often exceeding 0.85; however, external validation was rare and real-world implementation limited. Conclusions: While AI applications in resuscitation demonstrate encouraging performance in prediction and decision support tasks, clear evidence of improved patient outcomes or routine clinical use remains limited. Future research should focus on prospective validation, equity in data sources, explainability, and seamless integration of AI tools into clinical workflows
Development of a contraction-based pain index (CONPAIN) to evaluate labor epidural analgesia effectiveness: a pilot proof-of-concept study
No full textBackground: Assessment of labour pain is essential to guide neuraxial analgesia, yet current tools such as the Numeric Rating Scale (NRS) are influenced by subjective variability. We developed and tested the Contraction Pain Index (CONPAIN), calculated as the percentage ratio of self-reported pain duration to contraction duration measured on external cardiotocography. We hypothesised that CONPAIN would show an early relative change from baseline than NRS in the first 10 minutes after dosing. Methods: In this exploratory, single-center pilot study, CONPAIN and NRS were recorded in 27 nulliparous women in active labor before and after initiation of epidural analgesia. Data collection started five minutes before the initial epidural bolus and continued for 20 min thereafter. The primary outcome was the temporal trend of CONPAIN relative to baseline; secondary outcome was the comparison of percentage change from baseline between CONPAIN and NRS and their correlation over time. Results: Both metrics decreased within the first five minutes. Median percentage change at 0–5 minutes was −27.96 % for CONPAIN vs. −7.14 % for NRS (P < 0.001); at 6–10 minutes, −48.99 % vs. −40.00 % (P = 0.027). Differences were not significant after 10 minutes. Conclusions: In this proof-of-concept study, CONPAIN showed greater relative changes compared to NRS during the first 10 minutes following initiation of labour analgesia, suggesting potential value in characterising the early dynamics of analgesic response. While these findings offer preliminary support for its clinical relevance, validation in larger populations is required
Validation in four-point bending tests of a viscoelastic model for laminated glass based on fractional calculus
No full textWe present a one-dimensional viscoelastic finite element model for laminated glass, employing fractional calculus to effectively capture the shear-coupling behavior of the polymeric viscoelastic interlayer between glass plies. The polymer relaxation curve is approximated using four power-law branches, which are sufficient to represent both the short-and long-term responses of most commercial materials. This ensures that Boltzmann's integral aligns with Caputo's definition of a fractional time derivative. The spatial FE discretization is incorporated into the weak formulation of the dynamic viscoelastic problem derived from Hamilton's principle. Time integration is performed using finite differences, with fractional derivatives approximated through the L1 formula. This allows to use a variable time-step, progressing in logarithmic scale, to balance the representation across the different power-law branches of the relaxation curve. The model is validated through four-point bending experiments on laminated glass specimens, involving loading at various strain rates and relaxation tests at different temperatures. Comparisons between experimental results and model predictions show strong agreement across a wide range of loading conditions, time scales, and temperatures. This demonstrates the model's ability to accurately simulate the coupled viscoelastic response of laminated glass under bending loads, establishing it as a valuable tool for structural analysis and design in building engineering
Mechanochemical Aerobic Activation of Metallic Copper for the Synthesis of 1,4‐Allenynes
No full textMechanical activation of zero-valent metals is emerging as a new paradigm in sustainable synthesis, opening up a broad swath of chemical space under more practical conditions than solution-phase methods. Contrary to its neighboring elements in the periodic table, copper has been significantly overlooked in this domain, especially for C.C bond formation. Herein, a mechanochemical method for synthesizing >25 previously unreported conjugated allenynes—a valuable scaffold in organic synthesis is presented—through copper-catalyzed homocoupling of propargylic esters. This approach utilizes ball milling to activate inexpensive zero-valent copper under solvent-minimized conditions, sourced from both powders and recycled waste materials, including wires and bolts, into catalytically active CuI species under aerobic conditions. The synthetic utility of the synthesized compounds is showcased through an unprecedented rhodium-catalyzed cyclocarbonylation and a gold-catalyzed cyclization reaction
E SE LA “COMMEDIA” AVESSE AVUTO UN'ALTRA LINGUA: Inf. I, 1-3 nella Translatio Dantis di Giovanni Bertoldi da Serravalle e di Matteo Ronto
No full textNel campo delle traduzioni latine della Commedia di Dante Alighieri durante l'era umanistica, Giovanni Bertoldi da Serravalle e Matteo Ronto incarnano due approcci distinti all'opera originale, pur condividendo lo stesso intento: universalizzare la Divina Commedia, ampliandone l'accessibilità a un pubblico sempre più vasto, affinché potesse trarne insegnamenti morali e politici. Allo stesso tempo, i loro sforzi miravano a promuovere la fama del sommo poeta oltre i confini italiani. Un'analisi dei primi tre versi dell'Inferno rivela che Giovanni Bertoldi da Serravalle attua una vera e propria translatio, essenziale nella forma: riproduce fedelmente il testo di Dante in prosa latina ritmica, riducendo al minimo gli abbellimenti retorici. Al contrario, Matteo Ronto crea un'opera letteraria, un'interpretatio che si pone in debito con la letteratura classica, a partire dall'uso dell'esametro. La sua traduzione si distingue per la raffinatezza stilistica e retorica, che si traduce in un tono elevato, a volte difficile da interpretare. Questo contributo si propone di mettere a confronto questi due risultati traduttivi, per evidenziarne le somiglianze e le differenze