Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography

A focused library of newly designed monomeric and dimeric naphthalene diimides (NDIs) was analyzed in its ability to recognize specific G-quadruplex (G4) structures discriminating duplex DNA. The best G4 ligands—according to an affinity chromatography-based screening method named G4-CPG—were tested on human cancer and healthy cells, inducing DNA damage at telomeres, and in parallel, showing selective antiproliferative activity on HeLa cancer cells with IC50 values in the low nanomolar range. CD and fluorescence spectroscopy studies allowed detailed investigation of the interaction in solution with different G4 and duplex DNA models of the most promising NDI of the series, as determined by combining the biophysical and biological assays’ data

PDMS ring-spring soft probe for nano-force biosensing

We present an innovative design for a flexible probe to study mechanisms of biological force sensing and force generation in the piconewton to micronewton range. Made of polydimethylsiloxane (PDMS) and employing a novel ring-spring section with adjustable size, the device works both as a force sensor and force actuator by precise calibration of its tunable stiffness and optical measurement of ring deformation. In addition, the tip geometry of the probe can be properly shaped to fit the anatomical profile of the sensory receptor of interest and to reproduce the in vivo stimulation. Finally, use of Finite Element Method (FEM) modal analysis confirms that the resonance frequencies of probes are outside the frequency range of interest for many sensory systems. © 2015 IEEE

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug-Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

Purpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017-March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with >= 2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool.Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients >50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with >= 2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with >= 2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients).Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/ VEL regimen was more frequently detected on elderly patients and on those with >= 2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy

Real-World Analysis of Outcomes and Economic Burden in Patients with Chronic Kidney Disease with and without Secondary Hyperparathyroidism among a Sample of the Italian Population

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p p p p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT

Tutela multilivello dell'ambiente ed economia circolare nell'industria alimentare

La raccolta di contributi dal titolo “Tutela dell’ambiente ed economia circolare nell’industria alimentare” a cura di F.E. Celentano, R. De Meo, M. Robles, si inserisce nelle attività del progetto “Valorizzazione dei sottoprodotti dell’industria alimentare ai fini dell’innovazione dei processi produttivi di mangimi tra benessere animale e sviluppo sostenibile” (Codice identificativo S18 - CUP: H99J21017650006) finanziato dall’Unione europea. L’«ambiente», lungi dal designare etimologicamente un asettico spazio circostante nel quale si trova una persona o un oggetto, diviene situazione «giuridica», poiché (antropica) «proiezione» della «persona», ove la «qualità» del primo rappresenta un infungibile attributo «esistenziale» inerente al «diritto alla qualità di vita» di quest’ultima. Ripensare, così, sub specie juris l’«ecologicamente impattante» comporta farsi carico anzitutto dell’inquadramento del fenomeno nell’attuale quadro costituzionale, riconoscendo che l’attore socialmente «eco-responsabile» da “contadino” dissodatore ma, per ciò stesso, sfruttatore «esclusivo» è chiamato a divenire “imprenditore” attento ad orientare lo sviluppo, in funzione del benessere collettivo. Di qui, l’opportunità di suddividere i contributi raggruppandoli in due sottoinsiemi. Il primo si focalizza sulle fonti di approvvigionamento alimentare, con la riscoperta – si direbbe «fisiocratica» à la Cantillon – del “valore-terra”, che impone un netto passo in avanti dal “dominicale” «diritto soggettivo» di natura ad una “adespota” «soggettività giuridica» della natura per via degli esseri che ne formano la biodiversità, come tale tutelabile secondo le sue plurime manifestazioni (purché) nei limiti di quanto «utilmente gestibile». Il secondo affronta la questione “valoriale”, posta con forza, e da ultimo, dall’Agenda O.N.U. 2030 per lo Sviluppo Sostenibile – i cui obiettivi strategici sono stati ampiamente ripresi dalle istituzioni euro-unitarie – nell’indicare la direzione di perseguire sempre più un consumo «critico», al fine precipuo di creare un mercato economicamente (e fiscalmente) «razionale» nella misura in cui sia, al contempo, promozionalmente «equo e solidale»