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The integration of renewable energy sources into the electricity system can contribute to the development of a low-carbon economy. However, due to the intermittency and non-programmability of these sources, problems related to the management of local electricity grids may occur. A possible solution or limitation to these issues is given by the electrical storage. In addition, in the next future, domestic micro-grids are expected to play a fundamental role in electric power networks, driving both the academic and industrial research interests in developing highly efficient and reliable conversion and storage technologies. In this study, the behavior of a small-scale hybrid energy system for hydrogen production and storage has been predicted, by means of a developed calculation model, and the operational strategy of the system has been optimized with the aim to maximize the hydrogen production. In addition, with the aim to maximize the overall solar-to-hydrogen chain efficiency, the whole system model has been applied to different operating scenarios, to identify the optimal management strategy to control it.

The worrying effects of climate change have led, in the last decades, to the improvement of innovative solutions for low greenhouse emission energy conversion, among which, is the use of micro-ORC (Organic Rankine Cycle) systems for distributed generation, in the framework of combined heat and power applications and renewables exploitation. However, micro-ORCs environmental impact, due to high GWP (global working potential) working fluid leak rate, is an issue still to overcome. Neverthless the interest in using new low GWP refrigerants and their blends is increasing, new fluids have not yet been properly tested into ORC. Numerical studies reveal that low GWP fluids do not always guarantee the same performance of typically used fluids, leading to indirect emissions related to the use of fossil fuels to compensate the lower power production. This study proposes to investigate performance and impact of an innovative micro-ORC test bench when working with HFCs (HydroFluoroCarbons), low GWP fluids and mixtures, with the main aim of comprehensively evaluating its impact due to both direct and indirect greenhouse gas emissions produced in a typical annual operation.

In the last years, international programs in diverse sectors and national frameworks have been driven by the need of a sustainable growth, in a green economy perspective. In order to reduce the energy losses/dissipations, as well as the fossil fuels employment and related pollutant emissions, indeed, the spread of combined heat and power units and/or renewable sources generators is promoted into both the electrical grids and the thermal networks but are often in conflict with the economic aspects. In this context, the optimal management of complex energy networks – including, in particular, smart district heating – may lead to the achievement of important goals from the environmental and sustainability viewpoints. The aim of this paper is to develop a preliminary methodology for the complete evaluation of complex energy networks, considering energy, economic and environmental aspects. With this purpose, a case study consisting in a network for the fulfillment of electrical and thermal needs of the connected users will be analyzed, considering different scenarios in terms of energy generation mix and operation and applying different optimization software. In addition, the carried out evaluations will allow to set the basis for the discussion about the future of energy policies and possible incentives towards the sustainable development of the energy sector.

In order to pursue the goals of de-carbonization and renewable sources exploitation, an efficient, cost-effective and environmental friendly employment of energy systems is mandatory. In this context, the ERA-Net funded Project ZEHTC (Zero Emission Hydrogen Turbine Center) has been developed, aimed at the realization of a pilot plant consisting in the world first gas turbine test facility making use of the power produced during turbine tests – along with renewables (solar in particular) – for hydrogen production and batteries storage. The produced hydrogen will be locally used to run the gas turbine, thus reducing its environmental impact. The aim of this paper is to present the results of the first steps of the project, consisting in the definition of an optimized grid and in the development of a calculation model for the optimal energy systems design. To this respect, the typology of energy systems to be included into the grid (in addition to the current set-up of the existing turbine test center) will be presented. In addition, the mathematical models specifically developed for each component, as well as the developed operational logic of the entire grid, will be presented and discussed in order to set the optimal size of each systems.

Abstract Background Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT. Results All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5–59.3] and 9 [6.7–11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8–20.6] and 3.9 mcg/mL [3.3–4.4], respectively. Median area under the time–concentration curve (AUC0 − 24) and average steady-state concentration (Css, avg) were 193.9 mcg h/mL [170.6–208.6] and 8.07 mcg/mL [7.1–8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC0 − 24/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of Css, avg 3–4 mcg/mL. Conclusions In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC90, but exceeding the safety Css, avg. limit. Trial registration This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133).

Abstract Background Despite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk–benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique. Methods The panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1–3 (disagreement) or 7–9 (agreement). Results Overall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described. Conclusions ATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged.

Proline-rich antimicrobial peptides (PrAMPs) have gained attention due to their antimicrobial properties and low cytotoxicity. B7-005, a small optimized PrAMP, exhibits a broader spectrum of activity than native PrAMPs, due to an antimicrobial mechanism based on inhibiting prokaryotic protein synthesis and destabilizing bacterial membranes. However, the toxicity and the in vivo efficacy of B7-005 remain poorly understood, so in vitro and in vivo microbiology and toxicology experiments were used to assess its suitability as an anti-infective agent. The incidence of resistance towards B7-005 by E. coli was lower than for other PrAMPs and antibiotics; moreover, it maintained antimicrobial activity in the presence of human serum. B7-005 exerted its antimicrobial effect at a much lower concentration than those causing harmful effects on four different cell types, such as membrane permeabilization or non-lytic depolarization of mitochondria. The latter effect may be related to the inhibition of eukaryotic protein synthesis by B7-005 observed in vitro. In a zebrafish embryo model, B7-005 was well tolerated and reduced mortality from pre-existing E. coli bacteraemia. Overall, B7-005 was safe for human cells and effective against systemic infection in vivo, making it a promising lead for developing new antibiotics.

Summary: Background: Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9. It was investigated if this mechanism may be an independent sepsis endotype. Methods: In this cohort study, 14 patient cohorts from Greece, Germany and Italy were studied. The cohorts were 2:1 randomly split into discovery and validation sets. Sepsis was defined by the Sepsis-3 definitions and blood was sampled the first 24 h from meeting the Sepsis-3 definitions. Concentrations of IFNγ, CXCL9, IP-10 (IFNγ induced protein-10), soluble CD163 and ferritin were measured. The endotype of IFNγ-driven sepsis (IDS) was defined in the discovery set as the combination of a) blood IFNγ above a specified cut-off associated with the minimal risk for immunoparalysis (defined as ≥8000 HLA-DR receptors on CD45/CD14-monoytes); and b) increase of CXCL9. Results were compared to the validation set. Findings: 5503 patients were studied; 3670 in the discovery set and 1833 in the validation set. IDS was defined as IFNγ more than 3 pg/ml and CXCL9 more than 2200 pg/ml. The frequency of IDS in the discovery set was 19.9% (732 patients; 95% confidence intervals-CIs 18.7–21.3%) and in the validation set 20.0% (366 patients; 95% CIs 18.2–21.9%). Soluble CD163, a marker of macrophage activation, was greater in IDS and IDS had features distinct from MALS. The mortality in IDS patients was 43.0% (315 patients; 95% CIs 39.5–46.6%) in the discovery set and 40.4% in the validation set (148 patients; 95% CIs 35.5–45.5%) (p = 0.44 compared to patients of the discovery set). IDS was an independent risk factor for death in the presence of other endotypes, severity scores and organ dysfunctions of the multivariate model [hazard ratio 1.71 (95% CIs 1.45–2.01) in the discovery set and 1.70 (95% CIs 1.34–2.16) in the validation set]. Decreases of IFNγ and CXCL9 blood levels within the first 72 h were associated with better outcome. Interpretation: IDS is a new sepsis endotype independently associated with unfavorable outcome. Funding: Hellenic Institute for the Study of Sepsis; Horizon 2020 project ImmunoSep; Swedish Orphan BioVitrum AB (publ) and German Federal Ministry of Education and Research.

This study examines the relationships between ascribed responsibility, uses and gratifications, behavioural involvement, and visit intentions among Sicilian tourists using virtual reality (VR) to explore Romanian rural ecotourism destinations. Utilizing the Uses and Gratifications theory, it investigates how VR content's informativeness, playfulness, and social interactivity impact user engagement and behavioural intentions. Findings reveal that higher ascribed responsibility enhances gratifications from VR experiences, which increases behavioural involvement, essential for ecotourism. However, ascribed responsibility alone does not directly influence visit intentions, indicating the role of additional factors. A significant contribution of this research is the identification of a serial mediation model where uses and gratifications and behavioural involvement totally mediate the ascribed responsibility-visit intention relationship. This model highlights the complex interplay between cognitive, affective, and behaviouralresponses, demonstrating that ascribed responsibility enhances uses and gratifications, leading to increased behavioural involvement and, ultimately, visit intentions. The study extends the Uses and Gratifications theory into VR and ecotourism, emphasizing environmental responsibility in media engagement. Practical implications include strategies for tourism marketers to foster environmental responsibility and for VR developers to create engaging, informative, and interactive experiences. Policymakers can use these insights to promote sustainable tourism through supportive VR content development.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Abstract Background In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. Methods A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. Results The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. Conclusions Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

Unlocking the potential of sustainable agriculture relies on innovative approaches such as recycling crop waste and exploiting wastewater. Herewith, human urine derivatives were integrated into the fertigation of soilless-grown lettuce. The effects were remarkable: not only did they impact primary metabolites such as amino acids, proteins, and sugars, but they also influenced secondary metabolites such as polyphenols and anthocyanins, along with antioxidant enzyme activity. K-struvite, a urine precipitate with CaO and NaOH, elicited responses comparable to those of the control NPK and correlated with high biometric values. Interestingly, urine precipitate–CaO and electrodialysis (ED) concentrate stimulated accumulation of leaf polyphenols and anthocyanins, while urine precipitate–CaO induced high ABTS antioxidant capacity, highlighting their potential to enhance antioxidant activity and nutritive quality. Moreover, hydrolyzed urine and aurin induced a significant boost of essential amino acid content, underlining their role in increasing the nutritive value of lettuce. However, they also correlated with higher levels of MDA, a marker of lipid peroxidation, and reduced APX activity, indicating the need for further optimization. These findings underscore the promising role of human urine as an organic component in soilless lettuce fertilization, paving the way for more sustainable and resource-efficient agricultural practices.