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Aim In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting.Methods A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact.Results The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305euro: 14,521,464euro in the first year, 33,007,064euro in the second and 55,163,777euro in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potenti

Objectives: To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE. Methods: A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017-2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied. Results: From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren's syndrome. Conclusions: The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition.

The neuropsychological characteristics of the cerebellar cognitive affective syndrome (CCAS) in congenital, non-progressive malformations of the cerebellum have been scarcely investigated, and even less is known for Joubert syndrome (JS), an inherited, non-progressive cerebellar ataxia characterized by the so-called molar tooth sign. The few studies on this topic reported inconsistent results about intellectual functioning and specific neuropsychological impairments. The aim of this research is to examine the neuropsychological profile of JS compared to other congenital cerebellar malformations (CM), considering individual variability of intellectual quotient (IQ) in the two groups. Fourteen patients with JS and 15 patients with CM aged 6-25 years were tested through a comprehensive, standardized neuropsychological battery. Their scores in the neuropsychological domains were inspected through descriptive analysis and compared by mean of MANOVA and ANOVA models, then replicated inserting IQ as covariate. The two groups showed a largely overlapping neuropsychological profile, consistent with CCAS. However, the JS group showed worse performance in visual-spatial memory compared to CM patients, although this difference was mitigated when considering IQ. These findings highlight a divergence between JS and other CM in visual-spatial memory, which might suggest a critical role of the cerebellum in recalling task-relevant memories and might inform rehabilitative interventions.

In the cognitive assessment of Schizophrenia Spectrum Disorders (SSD), the standard scoring method for Verbal Fluency (VF) tasks is the number of correct words produced. Finer-grained measures, such as the size of semantic clusters and the number of transitions between them, have been proposed to characterise the cognitive functions involved, but results based on human ratings are heterogeneous. The objective of this study was to develop a computational procedure based on Vector Space Models (VSMs) to assess the predictive ability of these fine-grained measures for class membership in SSD. A semantic VF task was administered to thirty-five people with SSD and a matched group of healthy participants, and their VF productions were characterised manually and using a set of ad-hoc algorithms. Computational estimates consistently showed higher predictive accuracy than models built on VF measures computed by a human rater and models built on the sole total number of words.

On September 15, 2022, Ethereum changed its consensus algorithm, moving from Proof-of-Work (PoW) to Proof-of-Stake (PoS). This event is commonly known as “The Merge”. While this change has considerably reduced the overall energy consumption, it has been observed that 40% of the first 1,000 blocks since then have been validated by a very limited amount of cryptocurrency holders. This raises serious questions about the decentralized nature of the system. To address this concern, and to mitigate the potential negative externalities of current Maximal Extractable Value (MEV) extraction strategies, the community has agreed to implement a permissionless, transparent, and fair ecosystem for MEV extraction. In this paper, after describing the new ecosystem, we perform an analysis of the blocks validated after Ethereum's “The Merge”. In particular, we analyze the actual distribution of validators by accounting for their activity both inside and outside the MEV ecosystem, and discuss how the scenario has changed in recent months.

Urban gardens are focal in metropolitan social-ecological infrastructure and yet they are spaces often threatened by urban development. In Berlin and Warsaw, major urban changes have prompted citizens to alter their attitudes toward the use of existing garden areas. This study tackles the socio-spatial phenomena of emerging grassroots projects and practices jointly implemented by groups of allotment and community gardeners, which are instrumental in envisioning new forms of common management and protection of garden spaces along urban transformations. The article investigates how cooperation between gardeners of different backgrounds influences allotments’ patterns of property and public accessibility. The focus is on a possible change of perspective regarding the use of closed allotment structures and the conceptualisation of a new form of hybrid urban landscape: an integrated garden. Our findings fit into the general debate on gardens as commons and new forms of green space selfgovernance.

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The DNA damage response (DDR) coordinates DNA metabolism with nuclear and non-nuclear processes. The DDR kinase Rad53CHK1/CHK2 controls histone degradation to assist DNA repair. However, Rad53 deficiency causes histone-dependent growth defects in the absence of DNA damage, pointing out unknown physiological functions of the Rad53-histone axis. Here we show that histone dosage control by Rad53 ensures metabolic homeostasis. Under physiological conditions, Rad53 regulates histone levels through inhibitory phosphorylation of the transcription factor Spt21NPAT on Ser276. Rad53-Spt21 mutants display severe glucose dependence, caused by excess histones through two separable mechanisms: dampening of acetyl-coenzyme A-dependent carbon metabolism through histone hyper-acetylation, and Sirtuin-mediated silencing of starvation-induced subtelomeric domains. We further demonstrate that repression of subtelomere silencing by physiological Tel1ATM and Rpd3HDAC activities coveys tolerance to glucose restriction. Our findings identify DDR mutations, histone imbalances and aberrant subtelomeric chromatin as interconnected causes of glucose dependence, implying that DDR kinases coordinate metabolism and epigenetic changes.

This article tries to analyze the musical interpretation focusing on the specific condition of the performer. Vulnerability plays a key role, as a manifold condition leading towards different fields of experience: the text, the Other, and the look of the others. The analysis of these three dimensions allows to delineate the first segments of a chain of vulnerability linked to some constitutive features of the musical interpretation. It thus becomes possible to deal with issues such as fear of the public or stage fright, meaning them as revelatory phenomena of a condition, that of the performer, which sheds light on our own humanity, rather than as individual psychodynamic problems.