Editoriale

TranScript è una rivista internazionale che si propone di essere un luogo di discussione sul tema della traduzione, con particolare attenzione ai secoli fra l’XI e il XV. Accogliamo con favore contributi sulla ‘traduzione’ dall’oralità alla scrittura, fra diverse tradizioni culturali, dal latino ai volgari e alle lingue moderne. TranScript is an international journal providing a forum for discussion on the theme of translation, with a special focus on the centuries spanning from the 11th to the 15th. We welcome contributions on the translation of cultures from orality to script, on the ‘translation’ among different cultural traditions, from Latin into vernaculars, and across modern languages

Exchangeable Self-Assembled Lanthanide Antennas for PLIM Microscopy

This is the published manuscript version of the following manuscript: Exchangeable Self-Assembled Lanthanide Antennas for PLIM Microscopy, Angew. Chem. Int. Ed. 2023, e202314595 doi: https://doi.org/10.1002/anie.202314595 This article may be used for non-commercial purposes in accordance with Wiley Sharing Policies. Supplementary Materials accompanying this article can be found on-line at the publisher’s site.Lanthanides have unique photoluminescence (PL) emission properties, including very long PL life- times. This makes them ideal for biological imaging applications, especially using PL lifetime imaging micro- scopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lantha- nide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous-soluble, lanthanide antenna, 8-methoxy-2-oxo- 1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self-assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self-assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well- established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging.Grant PID2020-114256RB-I00 funded by AEI/10.13039/501100011033Grant PID2019- 104366RB-C22 funded by AEI/10.13039/501100011033/ FEDER “Una manera de hacer Europa”Grants P21_00212, A-FQM-386-UGR20 and 2021/00627/001-FEDER_UJA_ 2020 funded by FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y UniversidadesCSIC grant 202180E073Acción 1 from Universidad de JaénFunding for open access charge: Universidad de Granada/CBUASpanish Ministerio de Educación y Formación Profesional for the FPU Ph.D. scholarshi

Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic

Exchangeable Self-Assembled Lanthanide Antennas for PLIM Microscopy

This work was supported by grant PID2020-114256RB-I00 funded by AEI/10.13039/501100011033;grant PID2019-104366RB-C22fundedby AEI/10.13039/501100011033/FEDER“Una manera de hacer Europa”;grants P21_00212,A-FQM-386-UGR20 and 2021/00627/001-FEDER_UJA_2020 funded by FEDER/Junta de Andalucía-Consejería deTransformación Económica,Industria,Conocimiento y Uni-versidades; CSIC grant 202180E073; and Acción 1 from Universidad de Jaén. Funding for open access charge: Universidad de Granada/CBUA.A.R.-A.thanks the spanish Ministerio de Educación y Formación Profesional for the FPUPh.D. scholarship.Peer reviewe

TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m 2, oxaliplatin 85 mg/m 2, L-leucovorin 200 mg/m 2, 5-fluoruracil 2400 mg/m 2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract Background Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration CheckMate 017: NCT01642004; CheckMate 057: NCT01673867

Arginine and Lysine Supplementation Potentiates the Beneficial β-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, β-hydroxy β-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes

Le parole del male. Materiali per un lessico della violenza

Non sempre la violenza viene percepita come tale. Spesso si nasconde alle spalle di teorie capaci di legittimarla, altre volte si accompagna a retoriche in grado di celarla. E così viene accettata, normalizzata, alimentata. Scavando nella storia sociale e politica e nella struttura semantica di alcuni termini chiave, i saggi raccolti in questo libro esemplificano la pericolosa ambiguità di pratiche e parole utilizzate, in passato come oggi, in queste strategie dell'inganno. E suggeriscono l'urgenza di una sistematica ricognizione critica dei nostri lessici