University of Udine
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Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence
No full textSpinal muscular atrophy is a severe neuromuscular disorder caused by mutations in the survival motor neuron 1 gene, leading to progressive motor neuron degeneration. Over the past decade, disease-modifying therapies targeting the survival motor neuron pathway—nusinersen, onasemnogene abeparvovec, and risdiplam—have significantly transformed the clinical landscape of spinal muscular atrophy. Despite their common therapeutic goal of restoring functional survival motor neuron protein levels, these agents differ markedly in their molecular design, route of administration, pharmacokinetic behavior, and population-specific efficacy. This narrative review provides a comprehensive synthesis of pre- and post-approval pharmacokinetic data from pivotal trials, real-world studies, and population-based modeling. Nusinersen, an intrathecal antisense oligonucleotide, demonstrates prolonged cerebrospinal fluid exposure and slow systemic clearance. Onasemnogene abeparvovec, a single-dose gene therapy, shows sustained survival motor neuron expression mediated by adeno-associated virus 9 vector delivery and episomal persistence in nondividing neurons. Risdiplam, an orally administered survival motor neuron 2 splicing modifier, exhibits systemic bioavailability with reliable central nervous system penetration and predictable pharmacokinetics across age groups. Elimination of gene products and oligonucleotides is a multifaceted process involving enzymatic degradation, immune responses, and excretion through the kidneys or liver. We further discussed how interindividual variability, age, survival motor neuron 2 copy number, and immunological factors influence pharmacokinetic–pharmacodynamic relationships. Personalized treatment strategies for spinal muscular atrophy are increasingly being guided by advances in pharmacokinetic modeling. As the field evolves, biomarker-based monitoring and combination therapies are emerging as promising complementary approaches. With growing clinical experience and an expanding body of pharmacokinetic research on targeted therapies, there is strong potential to further refine treatment strategies—ultimately making spinal muscular atrophy care more effective, safer, and more accessible for patients worldwide
Circulating tumor DNA in the diagnosis of ovarian cancer: a systematic review
No full textObjective: Ovarian cancer (OC) remains a leading cause of gynecologic cancer mortality worldwide, largely due to late-stage diagnosis and limited early detection tools. Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker with the potential to improve diagnostic accuracy through detection of tumor-specific genetic and epigenetic alterations. Methods: This systematic review aimed to evaluate the diagnostic accuracy of ctDNA in detecting OC compared to healthy controls or benign conditions. A comprehensive literature search was conducted across PubMed, Web of Science, and EBSCO databases through April 2024, including studies that assessed sensitivity, specificity of ctDNA assays in plasma or serum samples. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. PROSPERO registration number: CRD42024590089. Results: Nineteen studies met inclusion criteria, employing a variety of molecular techniques including polymerase chain reaction-based methylation assays (73.7%) and sequencing methods (whole genome sequencing/next-generation sequencing) (21%), targeting single genes or multi-gene panels. Diagnostic accuracy of ctDNA varied, with sensitivity (40.6%-94.7%) and specificity (56%-100%) ranging broadly, but often outperforming CA125, particularly in early-stage. Concordance between ctDNA and tumor tissue ranged from moderate (r = 0.428) to strong (r = 0.771). Conclusions: Although heterogeneity across studies precluded meta-analysis, narrative synthesis suggests that ctDNA may offer an improved early detection capability over CA125, through methylation and copy number variation analyses. Further controlled prospective studies are needed to validate the clinical utility of ctDNA as a complementary tool in OC detection
"Lallazioni" in musica. Dimensioni educative della libera improvvisazione vocale/musicale, dalla glossolalia alla poesia.
No full textL’articolo esplora un’area di confine tra educazione linguistica ed educazione musicale, proponendo attività che valorizzano una vocalità primaria, non necessariamente semantica, come terreno propedeutico alla poesia e alla musica. Muovendo dalle Nuove Indicazioni Nazionali (primo ciclo), l’autore osserva che l’insegnamento dell’italiano tende a privilegiare chiarezza, grammatica e razionalità, mentre le sezioni dedicate alla musica aprono esplicitamente a pratiche corporee, improvvisative e cooperative. In questo spazio educativo la vocalità glossolalica—fatta di lallazioni, fonemi, suoni, ritmo—diventa un controbilanciamento a un eccesso di astrazione, integrando e arricchendo l’educazione linguistica.
Il quadro teorico intreccia musicologia, filosofia del linguaggio e pratiche poetiche.
La proposta didattica si concretizza in un percorso di cinque giochi progressivi
A study to investigate the potentiality of a biostimulant made by Fabaceae tissues and rich in triacontanol (long-chain alcohol) to enhance grapevine resilience under drought stress
No full textThe primary objective of this research was to investigate the potential benefits of a Fabaceae-based product rich in triacontanol (a long-chain alcohol) applied to Vitis vinifera cv. Merlot, on key physiological and productive parameters of grapevines under controlled water stress conditions. Specifically, the study focused on evaluating parameters such as photosynthetic activity, water use efficiency, and yield quality, while also monitoring the grapevines' physiological responses to water stress. By elucidating the effects of this treatment, the findings aim to contribute to developing innovative and sustainable solutions for modern viticulture. The experiment involved 40 Merlot grapevines grafted onto Kober 5BB rootstock. The vines were divided into two experimental groups: untreated control (NT) and treatment (T1), with 20 plants per group (4 replicates per group; 52 m2 per plot) following a randomized block design.
Net photosynthetic rate (A), stomatal conductance (gs), transpiration rate (E), and internal CO2 concentration (ci) were measured on three replicates per treatment (8 leaves per treatment) between 8:30 and 10:30 a.m. on fully expanded, healthy leaves between the 5th and 10th internodes of a central shoot. A portable photosynthesis system (Li-6400XT, Li-Cor Inc.) was used with a photosynthetic photon flux density (PPFD) of 1,200 μmol m−2 s−1, CO2 concentration set to 400 μmol mol−1, and relative humidity (RH) maintained at 65%. The qualitative parameters of the grape skin were also evaluated with rapid field spectroscopic and rheological systems.
T1 showed a significant improvement in WUE compared to NT, while NT recorded higher evapotranspiration (E), indicating greater water loss in untreated plants. Furthermore, all analysed genes exhibited significantly higher activation in T1 plants compared to NT. This suggests that the treatment triggered molecular mechanisms associated with water stress resistance. Finally, no differences were observed in total polyphenol concentration in grape skins between T1 and NT during the phenolic ripening curve, suggesting the treatment did not influence secondary metabolite accumulation under the tested conditions.
In conclusion, T1 (Fabaceae-based product rich in triacontanol) appears to offer significant advantages in managing water stress by improving WUE and activating stress-response genes, making it a promising tool for sustainable viticulture. However, its neutral impact on polyphenol content warrants further investigation to understand its broader implications for fruit quality and marketability
Repair Versus Replacement in Mitral Valve Papillary Muscle Rupture: A Multicenter Study
No full textObjectives Papillary muscle rupture (PMR) is a rare but potentially fatal mechanical complication after acute myocardial infarction (AMI). Although surgery is considered the gold-standard treatment for post-AMI PMR, the optimal surgical strategy remains unclear. Methods Data from post-AMI PMR patients submitted to mitral valve replacement (MVR) or mitral valve repair (MVr) surgery in the period between 2001 and 2019, from 20 international centres, were collected in the CAUTION study database. In-hospital and long-term post-discharge mortality were the endpoints. A multivariable logistic regression model was used to determine mortality independent factors. Results The patient cohort available included 218 patients. MVR was the most frequent type of surgery (81.6%). Complete PMR was more common in the MVR group (71.9%, . 008), while partial PMR was more frequent in MVr patients (75%, . 008). In-hospital mortality rate was 25.8% in the MVR subgroup and 20% in MVr subjects (. 440). In MVR subgroup, concomitant coronary artery bypass grafting (CABG) was associated with lower in-hospital mortality (n = 20/96, 21%) than no concomitant CABG (31.7%, . 035). Survival at 1, 3, 5, and 10 years was 59.3%, 55.9%, 53.1%, 46.9% in the MVR group and 59.9%, 56.8%, 54.1%, and 43.2% in MVr patients, respectively, with no statistical differences (. 474). Patients underwent MVr surgery, and 1-, 3-, 5-, and 10-year survival was 79.8%, 75.4%, 68.5%, and 37.5%, respectively, when CABG revascularization was performed, while no CABG survival was 16.7%, 16.7%, 8.3%, and 8.3% (P <. 001). Conclusions MVR is the most commonly performed in complete post-AMI PMR and MVr in partial PMR. No differences were observed regarding in-hospital and long-term mortality in the 2 surgical groups, and no independent factors were associated with overall mortality. Concomitant CABG was associated with higher in-hospital survival. Clinical Registration Number Clinicaltrials.gov, NCT03848429
Revisiting Yttrup and Abramsson’s Limit Analysis Model for Steel Screw Piles in Sand
No full textThis work stems from the curiosity stimulated by a paper by Yttrup and Abramsson, which appeared in the journal Australian Geomechanics in 2003. Their work proposes a kinematic limit analysis method to compute the ultimate strength of steel screw piles in sand when first the bending and then the plastic collapse of the pile helix occurs. It is accompanied by insightful comments drawn from geotechnical design experience. The paper has both academic and professional impact as it is cited in scientific journals and used in engineering practice in Australia and New Zealand. However, the original paper is quite brief in its exposition. Here, Yttrup and Abramsson’s model is critically reconstructed, providing guidance that can help avoid potential pitfalls in its application. A variation of the model is proposed. Then, the calculated results are discussed and compared with experimental results, starting with those of the original paper. This work hopes to contribute to enhancing the appraisal, adoption, and utility of Yttrup and Abramsson’s model in design practice and in subsequent studies
Tailor-made protein-rich bread for the elderly: integrating sensory preferences with nutritional and technological goals
No full textThis study aimed to evaluate the mechanical and sensory characteristics of a functional bread, and secondarily examined the attitudes and consumption habits of elderly people toward legumes to assess the potential acceptance of pea protein–based bread in this group. Experimental breads were made by replacing 5% of wheat flour with pea protein concentrate, either untreated or processed via high-pressure homogenization. The breads showed a homemade, heterogeneous appearance, which was appreciated by elderly consumers. They qualified as a “source of protein,” had lower sodium content, and featured a darker crust due to the Maillard reaction while keeping acceptable sensory attributes. Textural analysis indicated that breads with untreated pea protein were firmer and chewier than commercial ones. However, sensory tests showed that the experimental breads received higher liking scores, highlighting their appeal. Overall, adding pea protein enhanced nutritional value without affecting sensory quality, supporting its use to promote elderly nutrition and sustainability