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Currently 1.3 billion individuals globally engage in smoking, leading to significant morbidity and mortality, particularly among diabetic patients. There is urgent need for a better understanding of how smoking influences antidiabetic treatment efficacy. The review underscores the role of cigarette smoke, particularly polycyclic aromatic hydrocarbons (PAHs), in modulating the metabolic pathways of antidiabetic drugs, primarily through the induction of cytochrome P450 (CYP450) enzymes and uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), thus impacting drug pharmacokinetics and therapeutic outcomes. Furthermore, the review addresses the relatively uncharted territory of how smoking cessation influences diabetes treatment, noting that cessation can lead to significant changes in drug metabolism, necessitating dosage adjustments. Special attention is given to the interaction between smoking cessation aids and antidiabetic medications, a critical area for patient safety and effective diabetes management. This scoping review aims to provide healthcare professionals with the knowledge to better support diabetic patients who smoke or are attempting to quit, ensuring tailored and effective treatment strategies. It also identifies gaps in current research, advocating for more studies to fill these voids, thereby enhancing patient care and treatment outcomes for this at-risk population.

The Carte archéologique nationale (National Archaeological Map) is a digital inventory of archaeological heritage within French territory, under the responsibility of the Regional Directorates of Cultural Affairs (Direction Régionale des Affaires Culturelles: Drac) –and their Regional Archaeological Services (Services Régionaux de l’Archéologie: SRA). Managed by the Ministry of Culture, this inventory is linked both to a database called Patriarche, and to a GIS (Geographic Information System) providing the geographical location of the data. The Patriarche database is enriched mainly through the analysis of all the available archaeological reports (filed subsequent to completion of their related excavations), diagnostic operations and surveys prescribed by the SRA. For the former Rhône-Alpes region (Centre-Est of France), Patriarche currently includes 47,405 sites –called archaeological entities (EA)–, for an area that represents 12 departments and one metropolis.The database integrates a wide range of information, such as the types of remains, their chronology, the related artefacts, as well as information regarding context, operations, sources and protection. In total, Patriarche contains more than 500 archaeological features related to the aqueducts of the city of Lyon.Until now, only factual elements based on archaeological operation results were integrated into the National Archaeological Map. Results also mentioned by the archaeologist in the report , but based on broader reflection were not taken into account, even if they were crucial to understanding the aqueduct layouts.Accordingly, the person in charge of the Archaeological Map for the area in question undertook –in collaboration with Catherine Coquidé until 2015– the verification and enrichment of the data concerning the aqueducts of Lyon.This work, consisting of combining and analysing data related to the aqueducts, made it possible to verify the 475 archaeological entities known as "aqueducts" present in the Patriarche database. More precisely, the verification of an archaeological entity requires one to return to the original sources, the archaeological reports, inventories, or any other document, such as maps or other elements that would be archived within the SRA centre. The site is subsequently geolocated as accurately as possible on the land registry.This revision effort was carried out for the 180 archaeological operations related to four aqueducts, which were then integrated into the Patriarche database. It was found that almost 44% of the archaeological operations prescribed for the presumed presence of an aqueduct turned out to be “negative” in the archaeological sense, meaning no remains of the aqueduct in question were identified. This high percentage demonstrates that the knowledge of aqueducts’ layouts is still very partial and dispersed.This reconsideration of the data has enabled the SRA to acquire the general layouts for the four main aqueducts of Lyon, which are being updated as operations and archaeological research continues to progress. These new layouts allowed the SRA to be more efficient in the management of archaeological diagnostic surveys for the areas concerned by the aqueducts.Of the 52 communes concerned by Lyon’s aqueducts, only 22 have a so-called “Zone de Présomption de Prescription Archéologique (ZPPA)” which refers to a presumptive zone of archaeological preservation, directly linked to at least one aqueduct, and ten more ZPPA are currently being drafted. It is through these decrees that the majority of urban planning files reach the SRA and provide the opportunity to prescribe archaeological diagnostic surveys.The verification of aqueduct layouts allowed for the revision of 15 ZPPA “aqueduct”, which have been effective since 2016. This work now ensures better protection of this linear layout through more a precise targeting of archaeological operation prescriptions, which in turn engender improved knowledge of these vestiges.By changing the geometry of a ZPPA which has already been revised, new archaeological diagnostic surveys may thus also lead to changes, again related to the layout of the aqueduct. These cases are difficult for the SRA to handle, as the ZPPA decrees –weighty in their application–, cannot be repeatedly modified.Although the Archaeological National Map and the Regional Archaeological Service are at the centre of the inventory work related to the aqueducts of Lyon, the Map can only be enriched in collaboration with the entire scientific community. This cooperation leads to permanent revision of Lyon’s aqueducts layouts and of the archaeological knowledge of these remains in general.

Abstract Aims Heart failure is a chronic progressive condition, with considerable burden on patients' quality of life and economic burden for the healthcare systems. Before the approval of empagliflozin, there were no proven effective treatments for patients with heart failure with left ventricular ejection fraction (HF LVEF) > 40%. The aim of this study was to evaluate the cost‐effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone for patients with HF LVEF > 40%, from the perspective of the healthcare systems of the United Kingdom (UK), Spain, and France, and to quantify the healthcare costs for these patients. Methods and results A lifetime Markov cohort state‐transition model was developed based on discrete health states defined by Kansas City Cardiomyopathy Questionnaire‐Clinical Summary Score quartiles to track disease severity. Model inputs relied primarily on the EMPEROR‐Preserved trial data or obtained from published literature or country‐specific databases, as well as local guidelines for the requirements for the conduct of the economic evaluation of healthcare technologies. The total lifetime cost of receiving SoC per patient was £10 092, €15 765, and €14 958 in the UK, Spain, and France, respectively, which increased by £1407, €1148, and €1485, respectively, with the addition of empagliflozin to the SoC. Empagliflozin + SoC was associated with significantly reduced number of hospitalization for HF or cardiovascular death compared with SoC alone, which was a key driver offsetting its drug acquisition costs. The incremental cost‐effectiveness ratio per quality‐adjusted life year (QALY) gained was consistently favourable at £14 851, €11 706, and €15 447 in the UK, Spain, and France, respectively. Scenario analysis using the New York Heart Association functional class showed similar results. Probabilistic sensitivity analyses showed more than 50% probability for cost‐effectiveness for a willingness‐to‐pay (WTP) threshold of £/€20 000/QALY for the three countries. Conclusions Empagliflozin was found to be the first targeted treatment option that is clinically effective and cost‐effective for patients with HF LVEF > 40%. Prescribing empagliflozin with SoC to patients with HF LVEF > 40% is expected to improve clinical outcomes and patients' quality of life and substantially below accepted WTP threshold for the healthcare systems in the UK, Spain, and France.

ABSTRACTThis paper proposes a new interpretation of place brand as a multilevel threshold public good (MTPG) produced by the interaction of narratives from different geographical levels. Using an original dataset of Google trends and tweets from Italian provinces and regions, we test the hypothesis that place branding has a multilevel structure. We further test the MTPG framework applied to place branding, showing that place branding is influenced by different geographical levels which can trigger a spillover in terms of attractiveness if they contribute to crossing a threshold point. The results confirm the presence of a provision point in place branding, showing that the proposed MTPG framework fits the phenomenon. This article contributes to the literature on place branding and brands by providing a new lens through which to interpret the phenomenon, which may be useful for a better understanding and measuring of the interaction of branding strategies operating at different spatial scales.

Introduction: Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Due to the multifactorial nature of the disease, involving impairment of cholinergic neurotransmission and immune system, previous attempts to find effective treatments have faced challenges.Methods: In such scenario, we attempted to investigate the effects of alpha-glyceryl-phosphoryl-choline (α-GPC), a cholinomimetic molecule, on neuroinflammation and memory outcome in the triple transgenic mouse model of AD (3xTg-AD). Mice were enrolled at 4 months of age, treated orally with α-GPC dissolved in drinking water at a concentration resulting in an average daily dose of 100 mg/kg for 8 months and sacrificed at 12 months of age. Thereafter, inflammatory markers, as well as cognitive parameters, were measured.Results: Chronic α-GPC treatment reduced accumulation of amyloid deposits and led to a substantial re-balance of the inflammatory response of resident innate immune cells, astrocytes and microglia. Specifically, fluorescent immunohistochemistry and Western blot analysis showed that α-GPC contributed to reduction of cortical and hippocampal reactive astrocytes and pro-inflammatory microglia, concurrently increasing the expression of anti-inflammatory molecules. Whereas α-GPC beneficially affect the synaptic marker synaptophysin in the hippocampus. Furthermore, we observed that α-GPC was effective in restoring cognitive dysfunction, as measured by the Novel Object Recognition test, wherein 3xTg-AD mice treated with α-GPC significantly spent more time exploring the novel object compared to 3xTg-AD untreated mice.Discussion: In conclusion, chronic treatment with α-GPC exhibited a significant anti-inflammatory activity and sustained the key function of hippocampal synapses, crucial for the maintenance of a regular cognitive status. In light of our results, we suggest that α-GPC could be exploited as a promising therapeutic approach in early phases of AD.

Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.

Abstract Background Heart failure (HF) is associated with high morbidity and mortality, yet data on HF subtype (HF with reduced ejection fraction [HFrEF] and preserved ejection fraction [HFpEF]) in broad populations are lacking. Additionally, it is unknown whether current HF incidence and prevalence rates are consistent with historical data. Here, we estimate the incidence and prevalence of HF in England and describe the characteristics of patients with HF, both overall and by subtype. Methods This was a non-interventional cohort study based on data from the UK Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics data and Office for National Statistics mortality data. Patients aged ≥ 18 years who were registered in the CPRD Aurum database between 1st January 2015 and 31st December 2019 formed the base cohort, from which patients with a recorded chronic HF diagnosis (historical or incident) from 2015–2019 contributed to the incidence and prevalence calculations. Results The eligible denominator over the study period comprised 11,414,490 patients, from which 383,896 patients with HF were included as prevalent or incident HF cases. From 2015 to 2019, the incidence rate of newly diagnosed HF increased from 4.1/1,000 person-years to 4.9/1,000 person-years, and HF prevalence increased from 2.1% to 2.4%. Phenotype data were available for 100,224 (26.1%) patients, of which 68,780 patients had HFrEF and 31,444 had HFpEF (HFrEF/HFpEF ratio: 70.1%/29.9%). Comorbidity levels were high and broadly similar across HF subgroups. Conclusions Primary care recording of HF subtype is suboptimal, with more than 7/10 patients with HF lacking subtype data. In patients with a recorded subtype (n = 100,224), a HFrEF/HFpEF ratio of 70%/30% was observed. Comorbidity levels were high regardless of subtype. Between 2015 and 2019, we observed modest but consistent increases in the incidence and prevalence of chronic HF in adults, in line with historical data.

The “Vichy parenthesis” marked a turning point in the career of Jean Thibaud (1901-1960). He took over posts left vacant by the dismissals of Jean Perrin and Paul Langevin, two prominent figures in French physics whose political commitments were incompatible with the new regime. These posts taking were blamed by academics involved in the Resistance who saw Thibaud as a “collaborator”. We propose to follow Thibaud’s career path as closely as possible in the light of a personal “accommodation” strategy—a concept proposed by the historian Philippe Burrin to describe various forms of adaptation to the circumstances of the Occupation that we revisit in the context of this study.

Alzheimer’s disease (AD), marked by cognitive impairment, predominantly affects the brain regions regulated by cholinergic innervation, such as the cerebral cortex and hippocampus. Cholinergic dysfunction, a key contributor to age-related cognitive decline, has spurred investigations into potential therapeutic interventions. We have previously shown that choline alphoscerate (α-GPC), a cholinergic neurotransmission-enhancing agent, protects from Aβ-mediated neurotoxicity. Herein, we investigated the effects of α-GPC on the microglial phenotype in response to Aβ via modulation of the nicotinic alpha-7 acetylcholine receptor (α7 nAChR). BV2 microglial cells were pre-treated for 1 h with α-GPC and were treated for 24, 48, and 72 h with Aβ1–42 and/or α-BTX, a selective α7nAchR antagonist. Fluorescent immunocytochemistry and Western blot analysis showed that α-GPC was able to antagonize Aβ-induced inflammatory effects. Of note, α-GPC exerted its anti-inflammatory effect by directly activating the α7nAChR receptor, as suggested by the induction of an increase in [Ca2+]i and Ach-like currents. Considering that cholinergic transmission appears crucial in regulating the inflammatory profiles of glial cells, its modulation emerges as a potential pharmaco-therapeutic target to improve outcomes in inflammatory neurodegenerative disorders, such as AD.

Bacterial prostatitis infections are described as infections that are difficult-to-treat, due to prostate anatomic characteristics along with clinical difficulty in terms of diagnosis and management. Furthermore, the emergence of multidrug resistant (MDR) bacteria, such as extended-spectrum beta-lactamase (ESBL) producer Escherichia coli, also representing the main causative pathogen in prostatitis, poses major problems in terms of antibiotic management and favorable clinical outcome. Oral fosfomycin, an antibiotic commonly used for the treatment of uncomplicated urinary tract infections (UTIs), has been recently evaluated for the treatment of bacterial prostatitis due to its favorable pharmacokinetic profile, its activity against MDR gram-positive and gram-negative bacteria, safety profile, and multiple synergic effect with other antibiotics as well as the low resistance rate. This review addresses fosfomycin pharmacokinetics and pharmacodynamics and discusses the latest clinical evidence on its clinical use to treat acute and chronic bacterial prostatitis in hospitalized patients and in outpatients. As described in several reports, oral fosfomycin may represent a valid therapeutic option to treat susceptible germs commonly causing prostatitis, such as E. coli and other Enterobacterales as well as Enterococcus faecium, even as a first-line regimen in particular clinical settings (patients with previous treatment failure, with allergies or outpatients). Stronger data from further studies, including randomized controlled trials, would be helpful to establish the proper dosage and specific indications.

Two years have passed since WHO declared a pandemic state for SARS-CoV-2 infection. COVID-19 pathogenesis consists of a first viral phase responsible for early symptoms followed by an inflammatory phase, cytokine-mediated, responsible for late-onset manifestations up to ARDS. The dysregulated immune response has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through the induction of pro-inflammatory chemokines and cytokines, plays a key role in the development and maintenance of inflammation, acting as a pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, drugs targeting both IL-6 and IL-6 receptors have been evaluated in order to blunt the abnormal SARS-CoV-2-induced cytokine release. Sarilumab, a high-affinity anti-IL-6 receptor antibody, may represent a promising weapon to treat the fearsome hyperinflammatory phase by improving the outcome of patients with moderate-to-severe COVID-19 pneumonia. Further prospective and well-designed clinical studies with larger sample sizes and long-term follow-up are needed to assess the efficacy and the safety of this therapeutic approach to achieve improved outcomes in COVID-19.

The European Medicine Agency (EMA) has defined Adverse Drug Reactions (ADRs) as “a noxious and unintended response to a medicine”, not including poisoning, accidental, or intentional overdoses. The ADR occurrence differs based on the approach adopted for defining and detecting them, the characteristics of the population under study, and the research setting. ADRs have a significant impact on morbidity and mortality, particularly among older adults, and represent a financial burden for health services. Between 30% and 60% of ADRs might be predictable and preventable, emerging as a result of inappropriate prescription, drug chemistry inherent toxicity, cell-specific drug toxicity, age- and sex-related anomalies in drug absorption, distribution, metabolism, and elimination (ADME), and drug–drug interactions (DDIs) in combination therapies or when a patient is treated with different drugs for concomitant disorders. This is particularly important in chronic diseases which require long-term treatments. Rapid developments in pharmacogenetics/genomics have improved the understanding of ADRs accompanied by more accurate prescriptions and reduction in unnecessary costs. To alleviate the burden of ADRs, especially in the elderly, interventions focused on pharmaceutical principles, such as medication review and reconciliation, should be integrated into a broader assessment of patients’ characteristics, needs, and health priorities. Digital health interventions could offer valuable solutions to assist healthcare professionals in identifying inappropriate prescriptions and promoting patient adherence to pharmacotherapies.

Nowadays, many wireless applications require the exchange of electromagnetic waves through propagation environments that look like to stratified media to some extent. This may concern both natural scenarios, e.g., air/vegetation/ground, and artificial structures, like meta-materials, photonic devices, solar cells or systems-on-chip. The characterization of the layered propagation channel is therefore important for the design and deployment of effective devices and systems. To this aim, the Dyadic Green Function method has been often leveraged, although its use is usually limited to simple sources, like short dipoles or current elements. Furthermore, it seems unsuited to assess the dispersive properties of the channel, which are known to become important when high data-rate must be conveyed. In this paper, a ray-based approach to propagation inside layers is proposed. As the layered environment can be quite reverberating, a great number of rays may be needed, to the extent that the corresponding computational burden might be hardly afforded by general purpose ray tracing tools. Therefore, the ray tracing engine here presented is specifically conceived for the layered case, and mostly relies on analytical formulation. The accuracy of the model is checked against measurement carried out at chip scale at optical frequency, as a reference study case.

In this paper we want to describe current as well as heritage classifications and their effectiveness as tools to protect and preserve heritage sites in the official documents that have being written in those years. We want to emphasize that there is no inherent difference between the heritage values concealed in movable, immovable and intangible heritage assets. We are dealing with the same values differently expressed, interwoven with values of other sectors within development in one and the same spatial concept. Moreover, all heritage exists “somewhere”. Festivities, narratives, habits and customs are undertaken “somewhere” by a local population and locations that are meaningful for it. Local population makes no difference between the perception of landscape, town or village, or of movable heritage items in their churches, mosques, temples and museums, or of festivals, customs, habits and tales which live on in. They perceive this as a single synthetic whole, not segmented into analytic, rational categories of “immovable”, “movable” and “intangible”. This leads us to the insight that the interpretation and implementation of heritage values needs to take place across all heritage sectors together in an integral heritage approach, in which the responsables make take a common approach and forge the necessary synergies.

The root causes of the Italian decline lie in the distortions of collective action, which enhance the perverse behavior of both the elite and the people. The elites are “packs of wolves” that extract income and wealth to the detriment of society, shaping formal institutions. The people cultivate myriads of small special interests, operating as “swarms of locusts”, by circumventing and emptying formal institutions. The dualism of wolves and locusts derives from the many atavistic national dualisms and strengthens them.

Abstract In spite of machine learning has been successfully used in a wide range of healthcare applications, there are several parameters that could influence the performance of a machine learning system. One of the big issues for a machine learning algorithm is related to imbalanced dataset. An imbalanced dataset occurs when the distribution of data is not uniform. This makes harder the implementation of accurate models. In this paper, intelligent models are implemented to predict the hematocrit level of blood starting from visible spectral data. The aim of this work is to show the effects of two balancing techniques (SMOTE and SMOTE+ENN) on the imbalanced dataset of blood spectra. Four different machine learning systems are fitted with imbalanced and balanced datasets and their performances are compared showing an improvement, in terms of accuracy, due to the use of balancing.

Optical Wireless Networks on-Chip are an emerging technology recently proposed to improve the interconnection between different processing units in densely integrated computing architectures. In this work, we propose a 4 × 4 optical wireless switch (OWS) based on optical phased arrays (OPAs) for broadband reconfigurable on-chip communication. The OPA and OWS design criteria are reported. Moreover, the performances of the OWS are analyzed and optimized considering the electromagnetic propagation in on-chip multilayer structures, with different thicknesses of the cladding layer. The effect on the OWS behavior of a non-ideal distribution of the power in input to the OPA is also investigated by designing a 1 × 7 beam splitter, based on a single-stage multi-mode interference (MMI) device to be used as a single element of the OWS. Then, the MMI output signals are considered in input to the transmitting OPAs and the OWS performances are evaluated.

Currently 1.3 billion individuals globally engage in smoking, leading to significant morbidity and mortality, particularly among diabetic patients. There is urgent need for a better understanding of how smoking influences antidiabetic treatment efficacy. The review underscores the role of cigarette smoke, particularly polycyclic aromatic hydrocarbons (PAHs), in modulating the metabolic pathways of antidiabetic drugs, primarily through the induction of cytochrome P450 (CYP450) enzymes and uridine diphosphate (UDP)- glucuronosyltransferases (UGTs), thus impacting drug pharmacokinetics and therapeutic outcomes. Furthermore, the review addresses the relatively uncharted territory of how smoking cessation influences diabetes treatment, noting that cessation can lead to significant changes in drug metabolism, necessitating dosage adjustments. Special attention is given to the interaction between smoking cessation aids and antidiabetic medications, a critical area for patient safety and effective diabetes management. This scoping review aims to provide healthcare professionals with the knowledge to better support diabetic patients who smoke or are attempting to quit, ensuring tailored and effective treatment strategies. It also identifies gaps in current research, advocating for more studies to fill these voids, thereby enhancing patient care and treatment outcomes for this at-risk population. [ABSTRACT FROM AUTHOR]