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Background and Objectives: Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Methods: Three case–control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Results: Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84–0.91)], hospitalization [0.90 (0.88–0.93)] and mortality [0.48 (0.47–0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84–0.90), 0.86 (0.83–0.90), 0.55 (0.54–0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13–2.78) for short-acting DHPs; 1.19 (1.07–1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96–3.51) and 1.23 (1.08–1.42)]. Conclusions: The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Background and Objective: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality. Methods: The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008–2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012–2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates. Results: Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3–14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (− 1–38), 14% (7–20), 20% (13–26) and 13% (7–19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively. Conclusions: Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.

Deep analysis of regulative mechanisms of transcription and translation in eukaryotes could improve knowledge of many genetic pathologies such as retinitis pigmentosa (RP). New layers of complexity have recently emerged with the discovery that 'junk' DNA is transcribed and, among these, miRNAs have assumed a preponderant role. We compared changes in the expression of miRNAs obtained from whole transcriptome analyses, between two groups of retinal pigment epithelium (RPE) cells, one untreated and the other exposed to the oxidant agent oxidized low-density lipoprotein (oxLDL), examining four time points (1, 2, 4 and 6 h). We found that 23 miRNAs exhibited altered expression in the treated samples, targeting genes involved in several biochemical pathways, many of them associated to RP for the first time, such as those mediated by insulin receptor signaling and son of sevenless. Moreover, five RP causative genes (KLHL7, RDH11,CERKL, AIPL1 and USH1G) emerged as already validated targets of five altered miRNAs (hsa-miR-1307, hsa-miR-3064, hsa-miR-4709, hsa-miR-3615 and hsa-miR-637), suggesting a tight connection between induced oxidative stress and RP development and progression. This miRNA expression analysis of oxidative stress-induced RPE cells has discovered new regulative functions of miRNAs in RP that should lead to the discovery of new ways to regulate the etiopathogenesis of RP.

We report on an orbital and temperature dependent study of the onset of coherent quasiparticles in V2O3 single crystal. By using polarized infrared spectroscopy we demonstrate that the electronic coherence temperature is strongly orbital dependent, being about 400K for [Formula: see text] orbitals and 500K for the [Formula: see text]. This suggests that V2O3 low energy electrodynamics can be described in terms of two electron liquids differently renormalized by electronic correlations.

OBJECTIVE This study aims to evaluate the frequency of off-label use of ketorolac in Italy and the related suspected adverse drug reactions (ADRs) reported. METHODS All the suspected cases associated with ketorolac recorded in the Italian Pharmacovigilance database were retrieved. Case evaluations were carried out in order to identify the off-label use of ketorolac. Moreover, an analysis of the inappropriate use of ketorolac was conducted using the 'Arianna' database of Caserta local health unit. RESULTS Up to December 2014, 822 reports of suspected ADRs related to ketorolac were retrieved in the database. The use of ketorolac was classified as off-label for 553 reports and on-label for 269. Among the off-label cases, 58.6% were serious compared to 39.0% of on-label cases. Gastrointestinal events were more frequently reported with off-label use. The analysis of Arianna database showed that 37,729 out of 61,910 patients, were treated off-label. CONCLUSIONS The off-label use of ketorolac is widespread in Italy. This use increases the risk of serious ADR, especially in in case of prolonged duration of treatment and in elderly patients. The Italian Medicine Agency has decided to accurately monitor the appropriate use of the drug in Italy and, if necessary, take measures in order to minimize the risks.

The optical properties of a V4O7 single crystal have been investigated from the high temperature metallic phase down to the low temperature antiferromagnetic insulating one. The temperature dependent behavior of the optical conductivity across the metal-insulator transition (MIT) can be explained in a polaronic scenario. Charge carriers form strongly localized polarons in the insulating phase as suggested by a far-infrared charge gap abruptly opening at T_MIT = 237 K. In the metallic phase instead the presence of a Drude term is indicative of fairly delocalized charges with a moderately renormalized mass m* = 5m_e. The electronic spectral weight is almost recovered on an energy scale of 1 eV, which is much narrower compared to VO2 and V2O3 cases. Those findings suggest that electron-lattice interaction rather than electronic correlation is the driving force for V4O7 metal-insulator transition., 5 pages, 3 figures

Sulla scorta del libro di Claude Calame intitolato "Prometeo genetista" e di cui l'A. ha curato parte della traduzione italiana, viene indagata l'ampia gamma di significati propri del termine greco "techne" e della corrispondente radice. La ricerca riguarda in particolare il valore semantico proprio del termine, che si contraddistingue, alla luce dell'analisi condotta sulle più antiche attestazioni nella letteratura greca sino al IV secolo a.C., come una vera e propria "vox media". Il carattere sostanzialmente medio del termine, evidente nell'uso linguistico di autori quali Eschilo e Sofocle, si connota più o meno positivamente a seconda della valutazione del singolo autore, e in primo luogo rispetto alla possibilità di un uso socialmente e politicamente utile, nonché eticamente compatibile con i valori della comunità sociale e politica, delle arti tecniche.

Partendo dalla categoria politica di “eccezionalismo”, che è stata utilizzata per descrivere la politica estera degli Stati Uniti, soprattutto nel XX secolo, questo paper propone una analisi comparata con la politica ateniese di V secolo, soprattutto durante il suo impero marittimo: in tale contesto la nozione di “eccezionalismo” sembra adatta per comprendere alcuni aspetti della sua politica e i rapporti tra “eccezionalismo” e democrazia. Starting with the political category of 'exceptionalism', which has been used to describe US foreign policy, especially in the 20th century, this paper proposes a comparative analysis with 5th century Athenian policy, especially during its maritime empire: in this context, the notion of 'exceptionalism' seems suitable for understanding certain aspects of its politics and the relationship between 'exceptionalism' and democracy.

L’analisi della tradizione storiografica greca e di quella latina tardoantica sul soprannome imperiale Caracalla, legato alla veste di foggia barbarica introdotta dall’imperatore, indica due differenti spiegazioni dell’origine della denominazione, la prima legata agli eventi della campagna germanica del 213 ed alla successiva distribuzione alla plebs urbana delle vesti portate dalla spedizione, la seconda alla spedizione partica del 217 in occasione della quale l’imperatore avrebbe indossato un mantello ispirato a fogge barbariche. Le due tradizioni riflettono due originarie diverse connotazioni del soprannome, le quali tuttavia rispecchiano proprio le ambizioni ecumeniche dell’imperatore, che si alimentavano anche di forme di scambio interculturale. The analysis of the Greek historiographical tradition and that Late Antiquity Latin on the nickname imperial Caracalla, linked to the introduced barbaric style by the emperor, indicates two different ones explanations of the origin of the denomination, the first linked to the events of the German campaign of 213 and to subsequent distribution to the urban plebs of the clothes brought by the expedition, the second to the Parthian expedition of 217 on the occasion of which the emperor would have worn a cloak inspired by barbaric styles. The two traditions reflect two originating different connotations of the nickname, which however reflect precisely the ecumenical ambitions of the emperor, which also fed on forms of intercultural exchange.

Il saggio studia i problemi dell’ecologia a livello macro, meso e micro, nella Grecia antica, e illustra in particolare casi di inquinamento olfattivo e bellico, mostrando anche come le ‘grandi opere’ siano, per una tradizione di pensiero, segno di mentalità tirannica e arrogante. Mette in evidenza, inoltre, l’‘inquinamento’ della vita sociale e individuale, prodotto da un’economia fondata sull’arricchimento tendenzialmente infinito e considerata innaturale, in contrapposizione al benessere offerto da un’economia rispettosa dell’ambiente e delle esigenze comunitarie e individuali, considerata “conforme a natura”. Infine, presenta il modello politico delle Leggi di Platone e della Politica di Aristotele alla luce della nozione di limite in essi operante e confrontabile con quella che si trova oggi sia in qualche progetto politico occidentale sia nella visione del mondo dei popoli andini.

Si tratta di traduzione della Premessa all'edizione italiana del volume di Claude Calame, L'uomo e il suo ambiente. Al di là dell'opposizione natura/cultura

Background The incretin-based medicines GLP1 analogues (GLP1a) and dipeptidyl peptidase-4 inhibitors (DPP4i) are hypoglycaemic agents licensed for the treatment of type 2 diabetes mellitus (T2DM). Although these drugs possess comparable efficacy and low risk of hypoglycaemia, differences in terms of route of administration (subcutaneous versus oral), effect on body weight and gastrointestinal tolerabily can impact their actual use in clinical practice. This study aimed to describe the real-world utilization of incretin-based medicines in the Italian clinical practice. Methods A multi-database, population-based, descriptive, cohort study was performed using administrative data collected between 2008 and 2014 from three Italian geographic areas. Subjects aged ≥18 were selected. New users were defined as those with ≥1 dispensing of GLP1a or DPP4i during the year of interest and none in the past. Trends of cumulative annual incidence of use in the general adult population were observed. New users of GLP1a or DPP4i were respectively described in terms of demographic characteristics and use of antidiabetic drugs during 1 year before and after the first incretin dispensing. Results The overall study population included 4,943,952 subjects. A total of 7357 new users of GLP1a and 41,907 of DPP4i were identified during the study period. Incidence of use increased between 2008 (0.2‰ for both GLP1a and DPP4i) and 2011 (GLP1a = 0.6‰; DPP4i = 2.5‰) and slightly decreased thereafter. In 2014, 61% of new GLP1a users received once-daily liraglutide while 52% of new DPP4i users received metformin/DPP4i in fixed-dose. The percentage of new DPP4i users older than 65 years of age increased from 30.9 to 62.6% during the study period. Around 12% of new users had not received any antidiabetic before starting an incretin. Conclusions During the study period, DPP4i rapidly became the most prescribed incretin-based medicine, particularly among older new user. The choice of the specific incretin-based medicine at first prescription appeared to be directed towards those with higher convenience of use (e.g. oral DPP4i rather than subcutaneous GLP1a, once-daily liraglutide rather than twice-daily exenatide). The non-negligibile use of incretin-based medicines as first-line pharmacotherapy for T2DM warrants further effectiveness and safety evaluations to better define their place in therapy. Electronic supplementary material The online version of this article (10.1186/s12902-019-0334-y) contains supplementary material, which is available to authorized users.

All'interno delle opere biologiche, Aristotele disegna con frequenza le tappe dell'ontogenesi umana servendosi di immagini naturali e del confronto con altre forme di vita. L'embrione, ad esempio, «vive la vita della pianta» (Gen. an. II 2, 738 b 34-739 a 3; 739 b 34-740 a 4; 740 a 24-28). Il bambino condivide conformazione, maturità cognitiva ed esperienze degli animali privi di logos, e tanto più quanto minore è la sua età. Il bambino piccolo, ad esempio, strilla e gattona, e il suo corpo è ancora fuori asse rispetto alle dimensioni dell'universo (Part. an. IV, 10, 686 a 27-687 b 5); solo successivamente si approssima alla stazione eretta e migliora lentamente le sue abilità espressive e cognitive. Intorno all'età di quattordici anni maturano nell'individuo umano il seme, la più perfetta forma di residuo biologico; e la sua mente si apre ad accogliere un'intelligenza «divina» che proviene «dal di fuori». Se ne deduce che, per Aristotele, le tappe dell'ontogenesi umana ripercorrono in dettaglio le tappe della filogenesi naturale. Da ciò non dobbiamo dedurre un antropocentrismo della biologia di Aristotele. Le caratteristiche fisiche (stazione eretta, intelligenza, pollici opponibili) e psichiche dell'uomo (intelligenza intesa come nous, logos come espressione vocale) sono infatti non privilegi esclusivi, ma proprietà che derivano all'individuo umano dall'universo. La stazione eretta infatti orienta il corpo dell'uomo secondo i luoghi naturali nel cosmo (cfr. Preus 1975, 1990); e l'intelligenza attiva «è divina» e «viene dal di fuori» ma non appare perciò disincarnata (Gen. an. II, 3 736 b 22-731 a1). Esistono inoltre, in natura, forme di vita e di intelligenza superiori: gli astri (De Caelo II, 12, 292 a 18-21) e il cosmo (cfr. Laspia 2016), l'intera natura e il suo principio (Metaph. XII 7-9). L'intelligenza divina stessa è rappresentata da Aristotele come una forma di vita biologica (Laspia 2018). Da tutto ciò si desume che: 1. Aristotele è estraneo a ogni forma di dualismo mente/corpo. 2. la biologia aristotelica non è antropocentrica. 3. l'uomo è una forma di vita integrata nel cosmo e nella natura. 4. Per questa ragione le tappe dell'ontogenesi umana ricapitolano in sé tutte le forme di vita naturale sublunare, e culminano nella maturazione del seme e della facoltà riproduttiva da una parte, dell'intelligenza passiva, capace di rispecchiare in sé l'universo intero dall'altra. La vita umana si realizza dunque all'interno di un più vasto progetto, che coincide con il dispiegarsi della natura; solo al suo interno l’uomo può dirsi davvero felice.

C'è una grande confusione nela valutare il ruolo che le piante aliene invasive giocano nel ridurre la biodiversità. Vengono chiariti alcuni concetti spesso oggetto di mistificazioni.

IntroductionAnalgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use.MethodsThe Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID).ResultsFrom a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided.ConclusionAnalgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.