Objective: The purpose of the present study was to analyze the management of dental extractions in patients affected by coagulation disorders in order to prevent bleeding intraoperative and postoperative complications. Subjects and Methods: This study included 17 patients with a diagnosis of a coagulation disorder, who had been subjected to a single or multiple dental extraction. Recombinant activated Factor VII was administered in those patients who were affected by a deficit of factor VII ranged between 10,5% and 21%. The other patients were treated locally with tranexamic acid. Results: A total of 50 teeth were extracted, 7 by surgical extraction and 43 by simple extraction. Of the 17 patients included 9 of them suffering from factor VII deficiency, 5 from factor V deficiency, 1 from Glanzmann's thrombasthenia and 2 from Haemophilia A. Pretreatment with recombinant activated factor VII was performed on a total of 8 patients with factor VII deficiency; the remaining 9 patients underwent tranexamic acid treatment. 1 hemorragic postoperative complication was observed. Conclusions: Surgical and no surgical extractions appear to be a safe procedure for patients affected by coagulation disorders when appropriate prophylaxis is adopted.

Dyes, as indigo carmine have become indispensable to modern life being widely used in food, textile, pharmaceutical, medicine and cosmetic industries. Although indigo carmine is considered toxic and presents many adverse effects, it is heavily used in the food industry because the blue pigment is difficult to obtain from natural sources and is one of the most used dyes in the textile industry, especially for dyeing denim. Also, indigo carmine is one of the dyes used in medicine as diagnostic agent because it has impressive applicability in terms of diagnostic methods and surgical procedures. In the literature it is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, corneal and conjunctival disorders or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine, its use in various industries and medicine, the adverse effects of its ingestion, injection or skin contact, the effects on environmental pollution and its toxicity testing.

The majority of existing numerical simulations of the effect of bridge piers on water movement are based on a limited number of bridge piers at a laboratory scale. Furthermore, some 2D numerical simulations for actual bridge projects have deficiencies, including the use of overly large mesh sizes and an inadequate treatment of bridge piers. In this study, we compare three methods of structural mesh encryption, suspension mesh, and nonstructural mesh based on Delft3D, and apply the optimization scheme to a real bridge project. It is demonstrated that optimal results can be achieved by utilising a grid size comparable to the pier diameter (Dp) in the region away from the piers. In the vicinity of the piers, the grid cell size should be no larger than 1/9 Dp. The suspended grid technique (DD Boundary) can yield results consistent with those obtained using a full-area high-resolution grid, provided that the total number of grids can be reduced and the computational time is considerably reduced. In this study, the unstructured mesh (Deflt3D Flexible Mesh) scheme was unable to capture the oscillations of the wake flow behind the bridge piers. However, the application of the optimized scheme in bridge engineering has demonstrated its practical value. The findings of this study on mesh resolution and suspension mesh scheme can be applied to the Delft3D software and are also useful for other numerical simulation work.

The time series of daily new cases of Covid-19 infection in different zones of Italy, several European countries and New York City were analyzed in order to characterize the large fluctuations contained in them. The comparison shows that the time series share a similar evolution, although with delays of one or two weeks, with Italy that precedes the other countries. Correlation analysis indicates a strict resemblance between the time series of the first differences, which emphasize accelerations and slowdowns of the epidemic (e.g., correlation coefficient r=0.70 for Italian vs. worldwide data). According to Fourier analysis the signals have a dominant oscillatory component at a period of seven days, with minima located near the weekends. Some of the possible causes of this time modulation are discussed. In particular, it is hypothesized a delayed or missed recognition of a significant fraction of the new cases during the weekend, with possible consequences for the evolution of the epidemic.

Based on Chinese CDCP report on COVID-19, 14% of patients presented severe disease and 5% critical conditions. The average case-fatality rate was 2.3%, but mortality was as high as 49% in patients with critical illness. Serious life threatening thromboembolic complications have been found in 71·4% of non-survivors and micro/macro angiopathic coagulopathy has been found, also at autopsy, with highly increased neutrophil number, fibrinogen, concentrations of D-dimer and FDPs and NETs, ATIII decrease and normal number of platelets. A cytokine storm and interaction between inflammation and coagulation has been advocated as explanation of hypercoagulability. In this paper, it’s hypothesised that SARS-CoV-2 infection of alveolar cells induces recruitment of innate responder neutrophils, which release proteases and NETs inducing endothelial damage/endotheliopathy and imbalance of the four major proteolytic cascades (coagulation, complement, fibrinolysis and kallikrein) with prevalence of activators over inhibitors and consequent thrombotic complications. Platelets adhesion to damaged endothelium and the presence of ULVWF multimers, due to decreased ADAMTS13, contributes to the state of hypercoagulability. Neutrophil innate “unfriendly fire” response can be identified as the trigger of a “proteolytic storm”, responsible for subsequent well known prothrombotic condition and “cytokine storm”. The hypothesis explains also the pathology of recently described systemic “Kawasaki Disease like” vasculitis cases in Covid-19 young ill patients.

In estimating the maximum and minimum index void ratios for mixtures of sand and silt, the values of several empirical constants must be determined based on the type of sand and silt involved. These empirical constants are the filling coefficient, a, and embedment coefficient, b, both of which can be determined either through lab testing or correlations. These constants are then used in equations to predict the maximum and minimum index void ratios of the sand-silt mixtures. The study reported here developed simple correlations for estimating the filling and embedment coefficients using readily obtained laboratory data. These models were found to be excellent in developing filling and embedment coefficients that accurately (R2 values typically of 0.94 or greater.) predicted values of the index void ratios for sand and silt mixtures.

In the last two centuries, land use change (LUC) has been the most important direct changes driver for terrestrial ecosystems. To contrast the consequent ecosystems degradation, forward-looking spatial policies and target landscape and land-use planning processes, promoting a sustainable land use change, are needed. The present paper proposes a framework of action including different landscape planning and ecological approaches: from the spatial modelling to recognize the LUC and build different scenarios, to the ecosystem services (ESs) assessment to evaluate the possible environmental impacts. Three different scenarios were built: Trend, No-Tillage and Energy crops. The Sediment Delivery Ratio and Carbon Storage and Sequestration ESs were assessed and compared for each scenario. The aim of the paper is to support decision-makers and local communities into the landscape planning process. Results show that a regional development in line with past trend could lead to further land degradation. Instead, the two scenarios proposed in compliance with EU policies, could bring benefits only if related to moderate LUCs and respecting the naturally grass-vegetated land. From the local to global scale, a guided and shared LUC management allows implementing sustainable development, basing on a deep knowledge of physical-environmental but also social and economic issues.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

Scour depth around bridge piers plays a vital role in the safety and stability of the bridges. Existing methods to predict scour depth are mainly based on regression models or black box models in which the first one lacks enough accuracy while the later one does not provide a clear mathematical expression to easily employ it for other situations or cases. Therefore, this paper aims to develop new equations using particle swarm optimization as a metaheuristic approach to predict scour depth around bridge piers. To improve the efficiency of the proposed model, individual equations are derived for laboratory and field data. Moreover, sensitivity analysis is conducted to achieve the most effective parameters in the estimation of scour depth for both experimental and filed data sets. Comparing the results of the proposed model with those of existing regression-based equations reveal the superiority of the proposed method in terms of accuracy and uncertainty. Moreover, the ratio of pier width to flow depth and ratio of d50 (mean particle diameter) to flow depth for the laboratory and field data were recognized as the most effective parameters, respectively. The derived equations can be used as a suitable proxy to estimate scour depth in both experimental and prototype scales.

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3′ untranslated or coding regions of genes. They have been reported to play key roles in a wide range of biological processes. The recent remarkable developments of transcriptomics technologies, especially next-generation sequencing technologies and advanced bioinformatics tools, allow more in-depth exploration of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) including miRNAs. These technologies have offered great opportunities for a deeper exploration of miRNA involvement in farm animal diseases, as well as livestock productivity and welfare. In this review, we provide an overview of the current knowledge of miRNA roles in farm animal diseases with a particular focus on diseases of economic importance. In addition, we discuss the steps and future perspectives of using miRNAs as biomarkers and molecular therapy for livestock disease management as well as the challenges and opportunities for understanding the regulatory mechanisms of miRNAs related to disease pathogenesis.

In view of the preparation for a post-LHC collider, the high-energy physics (HEP) community started from 2010 to discuss various options, including the use of HTS for very high field dipoles. Therefore, a small program was set in Europe aiming at exploring the possibility of using HTS for accelerator quality magnets. Based on various EU funded programs, though at modest levels, has enabled the European community of accelerator magnets to start getting experience in HTS and addressing a few issues. The program was based on use of REBCO tapes to form 10 kA Roebel cables, to be used to wind small dipoles of 30-40 mm aperture in the 5 T range. The dipoles are designed to be later inserted in a background dipole field (in Nb3Sn), to reach eventually a field level in the 16-20 T range, beyond the reach of LTS. The program is currently underway: more than 1 km tape of high performance (Je > 500 A/mm2 at 20 T, 4.2 K has been manufactured and characterized, various 30 m long Roebel cables have been assembled and validated up to 13 kA, a few dipoles have been wound and tested, reaching at present 4.5 T in stand-alone (while a dipole made from race track coils with no-bore exceeded 5 T using stacked tape cable) and a test in a background field is being organized.

This study investigates uranium solvent extraction under AMEX process conditions. The use of pure extractants without diluents or phase modifiers allows not only to reduce the use of volatile organic compounds, but also to provide higher extraction yields without third phase formation. Pure extractants are protonated amines or quaternary ammoniums with suitable counter ion, which act at the interface between ion pairs and protic ionic liquids. The mixture of sulfates anion (SO42-) and bis(trifluoromethanesulfonyl)imide anion (NTf2-) revealed unexpected nonlinear extraction behaviors, which appear highly important to rationalize for optimized application. Spectroscopic analysis (NMR, UV-vis, FT-IR, and EXAFS) showed that uranium extraction occurs via protonated amine and three sulphates. Nonlinear extraction could further be interpreted by considering water and acid transfer between the two phases: at lower sulphate ratios, the release of acid from the organic phase into the aqueous phase was shown to influence the number of protonated amines in the organic phase, affecting uranium extraction before its enhancement. Furthermore, the extraction loss at higher sulphate ratios, was assigned to the destabilization of bidentate uranium-sulphate complexes due to a competition between water and sulphates.

A huge part of corrosion failures and even of catastrophes takes origin from a trivial mistake in either choice or connection of different materials, as well as from an inaccurate evaluation of the compatibility between materials an environment. The example shown in the present paper summarizes several wrong solutions due to the lack of knowledge of the basic rules of corrosion control. By chance, either the consequences of such mistakes were so precocious that it was possible to find a remedy during the construction, or they were happily so venial as to be tolerated. This paper is third in a series devoted to enhancing the need of a professional corrosion control design for infrastructures.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

This paper is intended at highlighting the main mechanical parameters controlling the behavior of the so-called "acceleration-sensitive" Non-Structural Components (NSCs). In the first part a short review of the current state of knowledge and the critical issues related to the prediction of the seismic response of NSCs is reported. Then, the paper presents the results of a numerical parametric analysis intended to capture the key features of the dynamic response of a two-degree-of-freedom (2DOF) system which is supposed to be representative of both the main structure and the "non-structural" component (NSC). Particularly, it allows to simulate the coupled behaviour of both main structure and NSC and evaluating their response. The main parameters controlling the dynamic response of NSCs emerge from this study, which could pave the way towards formulating more mechanically consistent relationships for evaluating the maximum accelerations induced by seismic shakings on NSCs.

The generation of vortices around bridge piers can lead to removal of riverbed materials from around piers, especially during flood events and heavy rainfalls, which can compromise the stability of the bridge and consequently its failure, if not properly detected and mitigated. Bridge failures pose serious threats to the local socio-economic and public safety and can cost lives. As such, real-time monitoring and early warning systems for scour-induced bridge failure can serve as a vital tool to protect the community and civil infrastructure against disastrous events. Vibration-base monitoring of bridge scour is an attractive option due to its low cost and relatively easy installation without the need to block the road and close the bridge to traffic. While limited number of previous studies have shown the capabilities of acceleration-based monitoring techniques in this area of research, they generally lack a rigorous framework for data analysis within and relating those to evaluate scour. This paper is an attempt to provide such framework that would enable a fast and low-cost analysis of vibration data within a physical modelling study on a simplified bridge pier. To achieve this, three experiments were conducted on an ideal single-pier scaled model bridge in a hydraulic flume, where water flows at a velocity near the critical velocity for the sand bed which in turn generates a scour hole around the pier. Then, the vibration data recorded using two mounted wireless accelerometers, were used to conduct an operational modal analysis through which the natural frequencies are extracted. The extracted natural frequencies and measured scour depths are then used to provide a chart that relates these two parameters. The results of this study showed the promising capability of the vibration-based data analysis in finding this relationship, indicating an up to around 30-50% reduction in natural frequencies as a result of around 50% scour ratio (ratio of maximum scour depth to buried depth), and beyond 50% scour ratio the natural frequencies remain constant. While the data presented in this paper are preliminary, they clearly show a promising potential for application in real-time monitoring of bridge stability under the effect of local scour and further works are underway to enrich the experimental data and empower the proposed methodologies at the laboratory scale.

The total lipid and protein content of the invasive caprellid amphipod Caprella scaura, from the biofouling communities of fish farm cages in the Pagasitikos Gulf were analyzed and compared among seasons. Proteins were the most abundant component (48.5 – 49.3%). Lipid content was relatively lower, with a wider range (6.7 – 34%) and showed a distinct seasonal fluctuation with high values in the winter population and a gradual decrease in spring and summer, with the lowest values in Autumn. Composition of the fatty acids profile was consistent among the seasons, with palmitic (16:0), Oleic (18:1n-9), Eicosapentanoic (20:5n-3)(EPA) and Docosahexanoic acid (22:6n-3 )(DHA) being the most abundant fatty acids. The presence of high levels of EPA and DHA fatty acids makes the species a potential candidate for use of these organisms in aquaculture.

In many instances paints interlayers delamination is attributed either to environmental or to application reasons. The composition as well as the structure, including morphology are always given for granted. The resin to pigment ratio, the surfactants, the quality of pigments and fillers (dimensions, shape, wettability, reactivity, homogeneity of distribution…) are not clearly required, defined and consequently checked. A fundamental article appeared in 1949 defining PVC and CPVC. In the following, it was quoted several times but not many improvements in the subject were shown: the subject was considered as obvious and unquestionable. We have tested some cases of coating delamination from big steel structures where other causes were either absent or not dominating if paint features were not taken into account. Many features of paint composition and structure were analyzed with both SEM and EDAX and a comparison with a carefully formulated paint was carried out.

In many instances paints interlayers delamination is attributed either to environmental or to application reasons. The composition as well as the structure, including morphology are always given for granted. Extended interlayer delamination was observed on two huge structures (>50000m2 each) causing more than $10 M damages. Overcoating time, UV exposure, Solvent retention and other possible environmental possible causes were considered. However, a careful morphological analysis showed that substantial differences existed in terms of the resin to pigment ratio, the surfactants, the quality of pigments and fillers (dimensions, shape, wettability, reactivity, homogeneity of distribution…) with respect to the sample used to certify suitability of the systems to climatic conditions C4 – C5 (ISO12944). The need to avoid any either voluntary or casual modification in both PVC and the kind and size of pigments to be used should be made evident as well as shown in some paragraph of existing Standards.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Hearing dysfunctions can be classified by type, degree, configuration, time of onset, aetiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and sensorineural. Conductive hearing loss (CHL) results from interference with the mechanical transmission of sound through the external and middle ear; it can be congenital, as a consequence of anatomic abnormalities, but it can commonly be acquired following middle ear inflammatory pathologies. Sensorineural hearing loss (SNHL) results from failure to transduce vibrations to neural impulses in the cochlean and is a consequence of an irreversible damage to the differentiated cells which make up the organ of hearing and the acoustic paths at various levels. Mixed hearing loss involves a combination of these two types in the same ear. Studies in neuroscience field have shown that the prevention of cell degeneration is only possible if all the factors taken at the different stages of stem cells’ multiplication and differentiation are administered together. We have demonstrated this in a recent study on the ability of SCDSFs to prevent neurodegeneration in hippocampal cells of the CA1 zone in mice. This study confirms previous findings demonstrating that early developmental zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues. These findings have open a promising way for the approaches promoting the rejuvenation and regeneration of different tissues, by-passing stem cell transplantation. In the present clinical trial we have used SCDSFs to study the possible reversion of neurosensory hearing loss, until now considered an irreversible condition.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

Mass mortality events and anthropogenic impacts were increasingly documented affecting Paramuricea clavata (Risso, 1826) during the last decades. These impacts enhance the settling of epibiontic organisms on the injured colonies. The epibiosis was studied by photographic sampling carried out on the granitic outcrops of the Tavolara Channel within the Tavolara-Punta Coda Cavallo Marine Protected Area (NE Sardinia) between 2017-2023 at 35-55 m. The number of colonies and percent surface involved in epibiosis, the specific richness of the epibiontic community and the temporal evolution of the phenomenon were investigated. Almost all the investigated gorgonians (93%) showed parts involved in epibiosis, with a high percentage of covering (one-third of the surface). Out of the 37 epibiontic species recorded, the most recurrent described an ecological succession dominated by hydrozoans, sponges, bryozoans, serpulids and the parasitic soft coral Alcyomiun coralloides. Nevertheless, single colonies studied through time revealed the unpredictability of the colonization process. The peculiar habitat of a high naturalistic value of the granitic outcrops hosting the P. clavata forests demonstrates a widespread suffering condition, supported both by environmental and anthropogenic sources of stress. Such considerations make it necessary to review the current zonation of the area, where the actual vulnerability and usability evaluations are based on obsolete information.

Trees, often referred to as the "lungs of the Earth," hold immense significance for both the natural world and human society. Their contributions span a multitude of ecological, environmental, economic, and social domains, making them essential components of a healthy and thriving planet. Phytoplasma association not only compromise tree aesthetics but also reduce photosynthetic capacity and overall vigour. Phytoplasma diseases also lead to increased tree mortality, altering ecosystem dynamics.This review article provides an in-depth exploration of phytoplasma diseases affecting trees worldwide, encompassing their epidemiology, symptomatology, impact and management strategies.

The aim of this study was to find a correlation between in vivo NIR scan patterns, oxidative status, and blood serum metabolites in rabbits fed diets protected or unprotected against oxidation. Rabbits does in groups of eight were fed for 9 weeks with diets containing linseed, rich in polyunsaturated fatty acids (LS), or linseed plus hazelnut skins, with antioxidant function (LS+HS), and palm oil, rich in saturated fatty acids (PO). The animals were examined at days 1, 31, and 63 using a smart SCÏO molecular sensor, a new miniaturized web-based wireless device, applied to the internal ear flap (NIR range 740-1070 nm). The hazelnut peels integrated diet protected the rabbits from the oxidative stress induced by the addition of unprotected polyunsaturated fats. NIR tomoscopy was variously correlated with serum parameters, lysozyme (R2=0.71), ROMs (0.47), cholesterol (0.49), triglycerides (0.40), and a multivariate Index of Oxidative Risk (0.67 [IOR]). The correlations suggested a close connection between the clustering of the diets according to the laboratory variables and the NIRS scan pattern clustering at the ending trial day, as shown by the highly significant odds ratios. Advantageous use of this simple, painless technique was evident in the planning phase, with no difference among the groups at the beginning of the study, but an effect size that evolved differently over time until the end of the study. In a practical validation of the SCÏO model in 92 commercial rabbit does, the average spread of the predicted IOR was 33% in lactating does (2.54±0.05) vs. dry does (1.91±0.07).

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

This paper discusses the development process regarding a group of four Augustana College seniors' research. The project is a mobile app for Android built-in Android Studio called Augustana Health and Dining. This application will improve the dining experience at Augustana College, provide additional health metrics for personal use and promote healthier lifestyles. The app features the menus of various on-campus dining areas, with calories, allergens, and other essential food information. It also includes a profile section that will display campus meal credits and a calorie counting metric that can be used to track calories consumed to display this information to users so they can make more informed choices on their meals and health.

Italian Directives recommends the good quality of natural mineral waters but literature data assert a potential risk from several microorganisms colonizing wellsprings and mineral water bottling plants. Aim of study is the identification of microorganisms from spring waters (SW) and bottled mineral waters (BMW) samples. Methods: Routine microbiological indicators, Legionella spp., Nontuberculous mycobacteria (NTM), protozoa (FLA) and physical-chemical parameters were assessed in 24 SW and 10 BMW samples performing culture methods and molecular tests as PCR and qPCR. Results: In 33 out of 34 samples no cultivable bacteria were isolated with the exception of 83 CFU/L of Mycobacterium gilvum, detected in one warm rich-mineralized SW. qPCR showed the presence of Legionella genomic units in 24% of samples (mean 2,9x10²±1,7x10² GU/L) and NTM genomic units in 18% of samples (mean 5,7x10^3±4,1x10³ GU/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1,3x10³ to 1,2x10⁵) and 42% of SW samples (counts from 1,1x10³ to 1,3x10⁴). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (mean 1,3x10⁴ ±2,9x10³ GU/L). Conclusion: The study highlights a low rate of microbial risk and the importance of risk assessment in natural mineral waters.

Hydration and fluids detected with bioimpdance can be confounderdby ecw expansion and overload. to estimates with sufficient accuracy body fat A confrontation with imaging and dxa is confirmatory

Current lines of research into mood disorders indicate that immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions, even when these mediators are produced in peripheral tissues. Elevated levels of circulating immune molecules have been consistently associated with depressive symptoms in a number of clinical populations and experimental models, to the extent that major depressive disorder (MDD) is now seen, at least in part, as a disorder of immunity. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy with the hope to improve treatment efficacy, particularly in those cohorts that do not respond well to standard medication. Such new practice requires the availability of biomarkers to tailor these new therapies to those most likely to benefit but also clear mechanisms of action describing the interaction between peripheral immunity and brain function. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease through peripherally induced sickness behaviour as the model for immune-induced MDD. After an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we propose a modified model of periphery-brain interaction that goes beyond the currently established view of interaction between peripheral cytokines and microglia cells as the driver of depression. Instead, we suggest that brain barriers are primary actors in the communication between body and brain and, as a consequence, in the pathophysiology of the disease. This model suggests novel biomarkers, novel targets for therapies as well as a novel mechanism for resistance to standard treatments.

The emergence of new plant diseases is an increasingly important concern. Climate change is likely to be among the factors causing most of the emerging diseases endangering forest and tree heritage around the world. Such diseases may be caused by latent pathogens or microorganisms cryptically associated with plants. The shift from a non-pathogenic to a pathogenic stage may depend on physiological alterations of the host, environmental changes and/or stress factors. In some woods of the Salento peninsula (Apulia region, Italy) sudden declines of holm oak plants (Quercus ilex L.) have been observed since 2016. The morphological and molecular characterization of representative fungal isolates associated with canker and necrosis in declining plants indicated that these isolates belong to the Botryosphaeriaceae family, and the most frequent species were Diplodia corticola and Diplodia quercivora, followed by Neofusicoccum vitifusiforme. In artificially inoculated young holm oak plants, both D. corticola and D. quercivora species produced intense and severe subcortical and leaf margin necrosis. N. vitifusiforme, although less aggressive, induced the same symptoms. Our research in addition to confirm the involvement of D. corticola in olm oak decline, represents the first report of D. quercivora as a new pathogen on Quercus ilex in Italy. Furthermore, to the best of our knowledge, we also found N. vitifusiforme as a new pathogen on Q. ilex for the first time.

In this work the general problem of the characterization of the topological phase of an open quantum system is addressed. In particular, we study the topological properties of Kitaev chains and ladders under the perturbing effect of a current flux injected into the system using an external normal lead and derived from it via a superconducting electrode. After discussing the topological phase diagram of the isolated systems, using a scattering technique within the Bogoliubov-de Gennes formulation, we analyze the differential conductance properties of these topological devices as a function of all relevant model parameters. The relevant problem of implementing local spectroscopic measurements to characterize topological systems is also addressed by studying the system electrical response as a function of the position and the distance of the normal electrode (tip). The results show how the signatures of topological order affect the electrical response of the analyzed systems, a subset of such signatures being robust also against the effects of a moderate amount of disorder. The analysis of the internal modes of the nanodevices demonstrates that topological protection can be lost when quantum states of an initially isolated topological system are hybridized with those of the external reservoirs. The conclusions of this work could be useful in understanding the topological phases of nanowire-based mesoscopic devices.

A maxillary totally edentulism was rehabilitated with one-piece implants starting from pre-existing totally removable denture. A 3D digital scan of the removable denture and upper and lower arches was performed. On this basis, a prototype with optimal esthetic and functional outcomes was re-alized and turned into a custom-made radiological stent with markers. The superimposition of STL and DICOM files allowed the virtual planning of one-piece implants ideal position. The stackable templates composed of a fixed component, namely base template, and removable components, were realized. The fixed component, once secured with anchor pins to the bone, was no longer removed. The removable components, screwed to the fixed component, were used to perform the implant surgery and the immediate prosthetic loading. A base template allowed for maintaining a fixed reference during the entire workflow, improving the transition between the digital project, the surgical procedure, and the prosthetic rehabilitation.

Over the years, the Egyptian temples at Luxor city have been intensely investigated, but most of these studies just focused on the classical sides of the archaeological and historical descriptions. Many of the environmental problems are inevitable results of the unplanned urban crawling around the monuments temples. This paper aims at assessing the environmental changes around some temples of Luxor City using Remote sensing and GIS techniques. In particular, a historical database made up of Corona and Landsat TM data have been investigated along with the new acquisitions of Quickbird2 and Sentinel2. Results from our investigation highlighted rapid changes in urban and agricultural areas, which adversely affected the Egyptian monumental temples causing serious degradation phenomena. Using the information obtained from our RS&GIS based analysis, mitigation strategies have been also identified for supporting the preservation of the archaeological area.

Nutrigenetics concerns individual differences in the reaction to food based on the genetic factors. Nutrigenomics analyses direct influences of nutrients on gene expression. Both terms are explained in our review article. Nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and of new ‘omic’ technologies. It is often difficult to appreciate their relevance in the practice of preventive approaches for optimizing health, delaying onset of disease and diminishing its severity. This paper represents a review about the current research on Nutrigenomics and Nutrigenetics, and provide scientific data for a new integrated clinical approach.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

Chronic wounds remain a significant clinical challenge, necessitating the exploration of novel therapeutic agents. Sedum telephium L. (syn. Hylotelephium telephium (L.) H. Ohba) leaf juice, known for its traditional medicinal uses, was evaluated for its wound healing properties. This study aimed to chemically characterize the leaf juice and assess its efficacy in promoting wound healing in vitro. Fresh leaves were collected and processed to obtain the juice, which was analyzed for polyphenols, flavonoids, polysaccharides, and proteins. Key bioactive compounds, including flavonols such as kaempferol glycosides and quercetin glycosides, were identified. The juice and its polysaccharidic fraction were tested on human keratinocytes (HaCaT) and fibroblasts (HFF-1) to assess cell viability, wound closure, and the production of growth factors and pro-collagen I. Our results indicated that the whole juice significantly enhanced wound closure in both cell types, with a marked increase in fibroblast growth factor (FGF) and LAP(TGF-β1) production in keratinocytes, highlighting its potential mechanisms of action. The polysaccharidic fraction alone showed limited efficacy, emphasizing the importance of the complete phytocomplex. These findings suggest that Sedum telephium L. represents a promising candidate in the setting of skin regeneration and repair.

Many apps have been created for food and health-related purposes, given our app’s secondary focus on calorie metrics and health, surveying existing apps, and previous approaches to curtailing the dining experience and promoting health will be helpful. An important aspect to consider when designing an app is a user engagement and how many people one can expect to use an app. Research has been done to study usage metrics and user experiences and opinions regarding mobile app usage, particularly in the health and diet app sector, which pertains to our app’s health features. Even with high user engagement, an app's overall utility and benefit also need to be considered and measured in some qualitative and quantitative sense. Numerous studies have been conducted to determine the effectiveness of food and diet apps on personal behavior. Although the app that is the subject of this proposal is not mainly a “dieting” app, its features, such as the calorie counter, can help facilitate these use cases for users inclined to do so.

The study takes into account different classes of tunnel boring machines (TBMs), with the aim of identifying correlation models which are meant to estimate, at a preliminary design phase, the construction time of a tunnel and to evaluate the mechanical and operational parameters of the TBMs, starting from the knowledge of the tunnel length and/or the excavation diameter. To achieve this goal, first of all a database was created, thanks to the collection of the most meaningful technical parameters from a large number of tunnels; afterward, it was statistically analysed through Microsoft Excel. In a first phase, forecasting models were identified for the three types of machines investigated, separately for compact rocks (open TBM) and fractured rocks (single and double shield TBM). Then, the mechanical parameters collected through the database were analysed, with the aim of obtaining models that take into account, in addition to the type of TBM, the geological aspect, and the type of rock characterising the rock mass. Finally, the validation of the study was proposed in a real case, represented by the Moncenisio base tunnel, a work included in the new Turin–Lyon connection line. The estimated values were compared with the real ones, in order to verify the accuracy of the experimental models identified.

Timely processing of observations from hyper-spectral imagers, such as SEVIRI (Spinning Enhanced Visible and Infrared Imager), largely depends on fast radiative transfer calculations. This paper mostly concerns the development and implementation of a new forward model for SEVIRI to be applied to real time processing of infrared radiances for the physical retrieval of surface temperature and emissivity. The new radiative transfer model improves computational time by a factor of ≈ 7 compared to the previous versions and makes it possible to process SEVIRI data at nearly real time. The new forward model has been applied for the simultaneous retrieval of surface temperature and emissivity in three infrared channels (8.7, 10.8, 12 μm). The inverse scheme relies on a Kalman filter approach, which allows us to exploit a sequential processing of SEVIRI observations. Based on the new forward model, the paper also presents a validation retrieval performed with in situ observations acquired during a field experiment carried out in 2017 at Gobabeb (Namib desert) validation station. Furthermore, a comparison with IASI (Infrared Atmospheric Sounder Interferometer) emissivity retrievals has been performed as well. It has been found that the retrieved emissivities are in good agreement with each other and with in situ observations, i.e. average differences are generally well below 0.01.

L-glutamate is one the most important excitatory neurotransmitter at central nervous system level and it is implicated in several pathologies. So, it is very important to monitor its variations, in real time in animal models’ brain. Amperometric biosensors have been used because of their very high temporal and spatial resolution, and because suitable for a short to mid-term implantation. The present study aimed to develop and characterize a new glutamate biosensor design that exploits the selectivity of Glutamate Oxidase (GluOx) for l-glutamate, and the capability of a small molecule as propylene glycol (PG) to influence and extend the stability and the activity of enzyme. Different designs were evaluated by modifying the main components in their concentrations to find the most suitable design. Moreover, enzyme concentrations from 100 U/ml up to 200 U/ml were verified and different PG concentrations (1%, 0.1% and 0.05%) were tested. The most suitable selected design was Pt_c/PPD/PEI(1%)₂/GlutOx₅/PG(0.1%) and it was compared to the same already described design loading PEDGE, instead of PG, in terms of over-time performances. PG has proved to be capable of determining an over-time stability of the glutamate biosensor in particular in terms of linear region slope (LRS) up to 21 days.

The aim of this systematic scoping review was to provide scientific evidence on the efficacy and methods of application of hyaluronic acid in the coverage of gingival recessions in terms of recession depth (RD) reduction, clinical attachment level (CAL) gain, probing depth (PD). An electronic search of the literature on the main databases was conducted. Initially, 405 articles were identified. Finally, 4 studies were included after the review process. It was not possible to perform a meta-analysis of the articles selected because of the differences among the surgical treatments and commercial formulations and compositions of hyaluronic acid. Both randomized controlled trials in this research examined Recession Type 1 gingival treated with coronally advanced flap. Recessions were treated with either modified coronally advanced tunnel or laterally closed tunnel combined with subepithelial connective tissue graft and hyaluronic acid (HA) in all case series. The studies analyzed no significant variation was found in PD variable. The results of RD reduction are in accordance with the literature. Modifications of CAL are connected to variations of RD. HA seems to improve the clinical outcomes of the described surgical treatment.

Data papers have emerged as a powerful instrument for open data publishing, obtaining credit, and establishing priority for datasets generated in scientific experiments. Academic publishing improves data and metadata quality through peer-review and increases the impact of datasets by enhancing their visibility, accessibility, and re-usability. We aimed to establish a new type of article structure and template for omics studies: the omics data paper. To improve data interoperability and further incentivise researchers to publish high-quality data sets, we created a workflow for streamlined import of omics metadata directly into a data paper manuscript. An omics data paper template was designed by defining key article sections which encourage the description of omics datasets and methodologies. The workflow was based on REpresentational State Transfer services and Xpath to extract information from the European Nucleotide Archive, ArrayExpress and BioSamples databases, which follow community-agreed standards. The workflow for automatic import of standard-compliant metadata into an omics data paper manuscript facilitates the authoring process. It demonstrates the importance and potential of creating machine-readable and standard-compliant metadata. The omics data paper structure and workflow to import omics metadata improves the data publishing landscape by providing a novel mechanism for creating high-quality, enhanced metadata records, peer reviewing and publishing of these. It constitutes a powerful addition for distribution, visibility, reproducibility and re-usability of scientific data. We hope that streamlined metadata re-use for scholarly publishing encourages authors to improve the quality of their metadata to achieve a truly FAIR data world.

The European Food Safety Authority (EFSA) has identified some risk factors for the occurrence of side effects linked to energy drinks (EDs) consumption by young people. Tachycardia, sleeplessness, caffeine addiction may be caused by excessive consumption of EDs during parties, sport matches, ect. EDs consumption has been evaluated in a sample of students in Italy together with some aspects of their lifestyle. The survey was performed in two high schools from September 2014 to June 2015. 583 students between 14 to 18 years were recruited and a standard questionnaire (EFSA checklist) was used to collect information on responders characteristics, beverages consumption, EDs with alcohol, and EDs and sports. 350 out of 583 responders (60%) consumed EDs and 146 out of 583 responders (25%) reported an occasional alcohol consumption. Despite 82 out of 146 alcoholic drinkers (56%) were EDs-alcohol consumers, only 70 out of 583 adolescents (12%) reported habitual EDs consumption. Moreover, 38 out of 379 (10%) of all physically active adolescents reported frequent EDs consumption before sportive trainings. Study results highlight the need for primary prevention measures in communication campaigns and training delivered by school to limit potential health threats related to excess of EDs consumption.

The principal function of science education is to introduce students to core scientific concepts and practices; nevertheless, it is now impossible, in such a complex world, to neglect the ethical issues involved. Placing school science in a broader context motivates students and equips them with valuable critical skills. A meaningful example was from palm oil production and pervasive use worldwide: plantations result in major deforestation occurring in species-rich tropical regions, making the palm oil issue global in scope and highly critical for several aspects related to sustainability. This paper reports a sequence of didactic activities starting from palm oil chemistry, gradually extended initially by a multidisciplinary approach, then by interdisciplinary-systemic maps and, ultimately, through a holistic vision - involving anthropological and cultural considerations about indigenous people of deforested territories. This progressive broadening corresponds to an ever-greater penetration into the personal sphere, a condition for a real ethical consciousness. The increased students’ awareness was tested by qualitative considerations, supporting the teaching dimension more than the learning one. Contrary to disciplinary contents, the emergence of moral feelings cannot be measured but only perceived. Therefore, chemistry provides key concepts essential for global competences development in order to deal with sustainability issues with an increased ethical awareness.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

This study refers to the optimization of a Selective Solar Absorber to improve the Sun-to-thermal conversion efficiency at mid temperatures in high vacuum flat thermal collectors. Efficiency has been evaluated by using analytical formula and a numerical thermal model. Both results have been experimentally validated using a commercial absorber in a custom experimental set-up. The optimization procedure aimed at obtaining Selective Solar Absorber is presented and discussed in the case of a metal dielectric multilayer based on Cr2O3 and Ti. The importance of adopting a real spectral emissivity curve to estimate high thermal efficiency at high temperatures in selective solar absorber is outlined. Optimized absorber multilayers can be 8% more efficient than the commercial alternative at 250 °C operating temperatures and up to 27% more efficient at 300 °C. Once the multilayer has been optimized the choice of a very low emissivity substrate such as copper allows to further improve efficiency and to reach stagnation temperature higher than 400 °C without Sun concentration.

Forest fires are part of a set of natural disasters that have always affected regions of the world typically characterized by a tropical climate with long periods of drought. However, due to climate change in recent years, other regions of our planet have also been affected by this phenomenon, never seen before. One of them is certainly the Italian peninsula, and especially the regions of southern Italy. For this reason, the scientific community, as well as remote sensing one, is highly concerned in developing reliable techniques to provide useful support to the competent authorities. In particular, three specific tasks have been carried out in this work: (i) fire risk prevention, (ii) active fire detection, and (iii) post-fire area assessment. To accomplish these analyses, the capability of a set of spectral indices, derived from spaceborne remote sensing (RS) data, is assessed to monitor the forest fires. The spectral indices are obtained from Sentinel-2 multispectral images of the European Space Agency (ESA), which are free of charge and openly accessible. Moreover, the twin Sentinel-2 sensors allow to overcome some restrictions on time delivery and observation repeat time. The performance of the proposed analyses were assessed experimentally to monitor the forest fires occurred in two specific study areas during the summer of 2017: the volcano Vesuvius, near Naples, and the Lattari mountains, near Sorrento (both in Campania, Italy).

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

This review is devoted to present the history of CARDIOSIM© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory system. The first version of CARDIOSIM© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on PC with disk operating system (MS-DOS) and was developed using the Turbo Basic language. The last version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce different pathophysiological conditions. The software simulator can reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It represents the whole circulation using a lumped-parameter model and enables the simulation of different cardiovascular conditions according to Starling’s law of the heart and a modified time-varying elastance model. Different mechanical ventilatory and circulatory devices have been implemented in the platform including thoracic artificial lung, ECMO, IABP, pulsatile and continuous right and left ventricular assist devices, biventricular pacemaker and biventricular assist devices. CARDIOSIM© is used in clinical and educational environment.

Lung cancer remains the leading cause of cancer-related death worldwide. The involvement of lymph nodes by the tumor has a strong impact on survival of patients. For this reason, lymphadenectomy plays a crucial role in the staging and prognosis of NSCLC, to define the most appropriate therapeutic strategies concerning the stage of the disease. To date, the benefit, in terms of survival, of the different extents of lymphadenectomy remains controversial in the scientific community. It is recognized that metastatic involvement of mediastinal lymph nodes in lung cancer is one of the most significant prognostic factors, in terms of survival, and it is therefore mandatory to identify patients with lymph node metastases who may benefit from adjuvant therapies, to prevent distant disease and local recurrences. The purpose of this review is to evaluate, the role of lymphadenectomy in early-stage NSCLC in terms of efficacy and accuracy, comparing systematic, sampling and lobe-specific lymph node dissection and analyzing the existing critical issue, through a search of the most relevant articles published in the last decades.

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on Electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. The study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

Optical characterization and thermal aging tests are performed on a sputter-deposited coating, consisting of SiO₂/Cr₂O₃/Cr/Cr₂O₃ layers, designed and developed as a selective solar absorber to be used for unconcentrated solar thermal applications. Both measurements are performed by using a home-made apparatus, which mimics a flat plate collector under high vacuum. A Performance Criterion (PC_η(T)), based on absorber efficiency is proposed, and a forecast of service lifetime is obtained. As a result of the thermal aging tests, the selective solar absorber under study appears to be highly efficient at mid temperatures (up to 573 K) and thermally stable at temperatures (up to 690 K).

The aim of the present study was to evaluate the effects on the presence and distribution of oxyntopeptic cells (OPs) and enteroendocrine cells (EECs) expressing GHR, NPY and SOM in the gastric mucosa of European seabass and seabream of dietary levels of bioactive peptides (BPs) obtained from salmon processing by-products (in silico approach). In this study, 27 seabass and 27 seabreams were divided into three experimental groups: a control group (CTR) fed a control diet and two groups fed different levels of BP to replace fishmeal: 5% BP (BP5%) and 10% BP (BP10%). The stomach of each fish was sampled and processed for immunohistochemistry. Some SOM, NPY and GHR-IR cells exhibited alternating “open type” and “closed type” EECs morphologies. In seabream gastric mucosa, the BP10% group (16.8 ± 7.5) showed a significant change in NPY-IR cell number compared to CTR (CTR 8.5 ± 4.8) and BP5% (BP10% vs. CTR P ≤ 0.01; BP10% vs. BP5% P ≤ 0.05). In seabream, SOM-IR cells in the BP 10% diet (16.8 ± 3.5) differed from those in CTR (12.5 ± 5) (CTR vs. BP 10% P ≤ 0.05) and BP 5% (12.9 ± 2.5) (BP 5% vs. BP 10% P ≤ 0.01). In seabass, EEC SOM-IR cells increased at 10 % BP (5.3 ± 0.7) compared to 5 % BP (4.4 ± 0.8) (5 % BP vs. 10 % BP P ≤ 0.05). The results obtained suggest that salmon BPs have a promising impact as circulating ingredients for seabass and seabream.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in Oncology be-cause of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein ex-tremely difficult. KRAS regulates development, cell growth, Epigenetically-dysregulated differ-entiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) and leads to an immunosuppressive tumor microenvironment (TME). In this context, the oncogenic mutation of KRAS induces an epigenetic program that leads to the initiation of PDAC. Several studies have identified multiple direct and indirect inhibitors of KRAS signaling. Therefore, KRAS dependency is so essential in KRASmu PDAC that cancer cells have secured several compensatory escape mechanisms to counteract the efficacy of KRAS inhibitors, such as activation of MEK/ERK signaling or YAP1 upregulation. This review will provide insights into KRAS dependency in PDAC and analyze recent data on inhibitors of KRAS signaling, focusing on how cancer cells establish compensatory escape mechanisms.

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.

Earthworms and soil microorganisms contribute to soil health, quality and fertility, but their importance in agricultural soils is often underestimated. This study aims at examining whether and to what extent the presence of earthworms [Eisenia fetida (Savigny, 1826)] affected the a) soil bacterial community composition, b) litter decomposition, and c) plant growth (Brassica oleracea L., broccoli; Vicia faba L., faba bean). We performed a mesocosm experiment in which plants were grown outdoors for four months with or without earthworms. Soil bacterial community structure was evaluated by a 16S rRNA-based metabarcoding approach. Litter decomposition rates were determined by using the tea bag index (TBI) and litter bags (olive residues). Earthworm number almost doubled throughout the experimental period. Independently of the plant species, earthworm presence had a significant impact on the structure of soil bacterial communities, in terms of enhanced α- and β-diversity (especially that of Proteobacteria, Bacteroidota, Myxococcota, and Verrucomicrobia) and increased 16S rRNA gene abundance (+89% in broccoli and +223% in faba bean). Microbial decomposition (TBI) was enhanced in the treatments with earthworms, and showed a significantly higher decomposition rate constant (kTBI) and a lower stabilization factor (STBI), whereas decomposition in the litter bags (dlitter) increased by about 6% in broccoli and 5% in faba bean. Earthworms significantly enhanced root growth (in terms of total length and fresh weight) of both the plant species. Our results show the strong influence of earthworms and crop identity in shaping soil bacterial communities, litter decomposition and plant growth. These findings could be used for developing nature-based solutions that ensure the long-term biological sustainability of soil agro- and natural ecosystems.

Most European cities are characterized by very large areas, often formed by buildings with low quality, from a series of point of view. The possibility of renovating them is strategic to improve both the quality of life and to the possibility of economic recovery for building companies. In the last decades, the attention of the scientific community has been addressed to the energy renovation, thanks to the strong activities of the European Community in this field. However, since a relevant part of the EC territory is at risk of earthquake, the possibility to combine both energy and seismic renovation actions may be strategic for many countries. In particular, Italy and Romania are linked by a common social tradition that springs from the Roman Empire. Nowadays, this link is stronger, thanks to common interests in social, cultural and business fields. Therefore, the investigation of possible synergies for seismic and energy renovation strategies may be really interesting for both countries. This paper represents the first step in this direction. After an overview of regulations and common practices for buildings with reinforced concrete structures, in both states, some key combined renovation interventions will be described and discussed, as well as advantages and perspectives of integrated renovation approaches.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

The boreal Hemisphere has been experiencing increasing extreme hot and dry conditions over the past few decades, consistent with anthropogenic climate change expectations. The continental extension of the phenomenon calls for tools and techniques capable of monitoring the global to regional scales. In this context, the satellite is the only system that can satisfy the need for global coverage. The main objective we have addressed in the present paper is the capability of infrared satellite observations helping to monitor the vegetation stress due to increasing drought and heatwaves in summer. We have designed and implemented a new water deficit index (wdi) that exploits satellite observations in the infrared to retrieve humidity, air temperature, and surface temperature simultaneously. These three parameters are combined to provide the water deficit index. The index has been developed based on the Infrared Atmospheric Sounder Interferometer or IASI, which covers the infrared spectral range 645 to 2760 cm-1 with a sampling of 0.25 cm-1. The index has been used to study the 2017 heatwave, which hit Continental Europe from May to October. In particular, we have examined Southern Italy, where Mediterranean forests suffer from climate change. We have computed the index's time series and show that it can be used to indicate the atmospheric background conditions associated with meteorological drought. We have also found a good agreement with soil moisture, which suggests that the persistence of anomalously high water deficit index was an essential driver of the rapid development and evolution of the exceptionally severe 2017 droughts.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

A new frontier in solar thermal panel technology can be a high vacuum collector, thick enough to be equipped with solar concentrators based on non-imaging optics, such as the Compound Parabolic Concentrators (CPC). The high vacuum technology guarantees higher operating temperatures thanks to the enhanced thermal insulation, which leads to pay particular attention to the absorber radiative emission. In this paper by means of numerical simulations we compare the efficiency of a flat selective solar absorber under high vacuum to the efficiency of a CPC under high-vacuum collector.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical pictures. This makes the treatment of depressive symptoms even more difficult since many pharmacological and pharmacokinetic interactions should be considered by physicians approaching the therapy. Hence, depression still represents a challenge for both psychiatrists and the other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies in antidepressant treatment is mandatory; even including revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. The results of a consensus of experts regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment is herein reported. This is based on the unique characteristics of this drug possibly delivering a rapid antidepressant action as compared to other selective serotonin reuptake inhibitors (SSRIs) as well as on its pharmacodynamic malleability and pharmacokinetic tolerability when used in the milieu of other drugs in treating comorbid depressive symptoms.

Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue, characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients, satisfying the 2013 ACR/EULAR classification criteria, were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), ac-tivity index, video-capillaroscopy, echocardiography, and lung function data were ana-lyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis and steatosis. Specifically, values ≥ 238 CAP ≤ 259 dB/m were considered consistent with mild steatosis (S1), 260 ≥ CAP ≤ 290 dB/m with moderate steatosis (S2) and ≥291 dB/m with severe steatosis (S3) Results The median age of patients was 51 years, with a median disease duration of 6 years. Median LS was 4.5 (2.9–8.3) kPa; 41 patients (69.5%) had no evidence of fibrosis (F=0), 16 (27.1%) displayed LS values between 5.2 and 7 kPa; only 2 patients (3.4%) had LS values >7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164–343). Overall, 39 patients (66.1%) did not show evidence of steatosis (CAP values <238 dB/m); 9 patients (15.2%) showed values consistent with mild (S1) steatosis (CAP value ≥238 ≤259 dB/m); 8 patients (13.5%) had moderate (S2) steatosis (CAP value ≥260 ≤290 dB/m); 3 patients (5.1%) were deemed to have severe steatosis (S3) due to CAP values ≥291 dB/m. Conclusions Only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Likewise, the prevalence of significant steatosis was low (5.1%) and depending on the same variables associated with fatty liver in the general population. TE was shown to be an easy and valuable method for detection and screening of liver fibrosis in SSc patients with no additional risk factors for liver disease.

Background: Interleukin (IL)-33 is a member of interleukin (IL)-1 family of cytokines which has been linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has direct effect on human gastric epithelial cells (GES-1) and on human gastric adenocarcinoma cell line (AGS) and gastric carcinoma cell line (NCI-N87), assessing its role in regulation of cell proliferation and cell cycle, apoptosis and necrosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Methods: cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assay, we also evaluated apoptosis by Caspase 3/8 Activity assay and Annexin V assays. Cell cycle were analyzed by means of Propidium Iodine assay and gene expression regulation was assessed by RT-PCR Profiling. Results: we found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell line, while it can stimulate proliferation and reduce apoptosis in normal epithelial cell line. These effects are also confirmed by the analysis of cell cycle gene expression which showed a reduced expression of proproliferative genes in cancer cells, in particular genes involved in G0/G1 and G2/M checkpoint. These results are confirmed by the gene expression analysis on surgical and bioptic specimens. Conclusions: the aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell type-dependent fashion.

The concept of gray-zone lymphoma (GZL) has been progressively refined since its in-troduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediasti-nal forms (PMBL). Officially recognized as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lym-phoma and classical Hodgkin lymphoma”, it was limited to tumours, which showed either morphologic features reminiscent of classical HL (CHL) but carrying a complete B-cell pheno-type or conversely provided with a PMBL morphology but revealing CHL phenotypic charac-teristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th Edition of the WHO Classification of Haemato-lymphoid Tu-mours, which have limited it to mediastinal neoplasms based on emerging molecular evidences. The aim of this review is to critically discuss the issue of GZL, also in the light of the suboptimal response to current therapies.

Allopolyploidy in plants involves the merging of two or more distinct parental genomes into a single nucleus, a significant evolutionary process in the plant kingdom. Transcriptomic analysis provides valuable insights into the fate of duplicated genes, evolutionary novelties, and environmental adaptations exhibited by allopolyploid plants. However, transcriptome profiling is challenging due to genomic redundancy, which is further complicated by the presence of multiple chromosomes sets and the variations among homoeologs and allelic genes. Prior to transcriptome analysis, sub-genome phasing and homoeology inference are essential for obtaining a comprehensive view of gene expression. This review aims to clarify the terminology in this field, identify the most challenging aspects of transcriptome analysis, explain their inherent difficulties, and suggest reliable analytic strategies. Furthermore, bulk RNA-seq is highlighted as a primary method for studying allopolyploid expression, with an emphasis on the critical steps of read mapping and normalization in differential gene expression analysis.

In the aerospace sector, structural and non-structural components are usually subjected to a wide range of environmental conditions. Although lightweight, the use of composite parts for these applications is restricted, due to their poor performance in severe environmental conditions. Specifically, moisture can seriously damage the materials' performance, reducing their mechan-ical, thermal, electrical, and physical properties as well as the service time. A strategy to improve the materials’ resistance in humid environments is the use of protective lightweight barrier coatings to reduce the diffusion of gases and/or liquids in composites. Nanolamellar nanocom-posite characterized by the high in-plane orientation of nanoplatelets effectively works as barrier structures by generating tortuous paths for molecule diffusion. In this work, the effectiveness of protection against water uptake of nanocomposites reinforced with Graphite NanoPlatelets (GNPs) at high filler content (70, 80 and 90%wt) for Kevlar sandwich panels of a nacelle engine of an ATR42 aircraft has been investigated. Moisture uptake and Ground Air Ground (GAG) tests were carried out in an environmental chamber to reproduce temperature and relative humidity profiles representative of a real-scale application for a regional aircraft composite part. The high filler content of the graphene films ensures a high level of tortuosity by delaying and reducing moisture absorption by –71% compared to the unprotected panel, showing good barrier properties.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering with major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcome. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite double the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of a new approach. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach underlying BPD in MDD

Multilayer absorbers based on Cr2O3 and Cr, designed to improve the Solar-to-thermal conversion efficiency at mid temperatures in high vacuum flat thermal panel, are fabricated via sputtering deposition on bulk copper substrates and characterized by thermal and optical analysis. The refractive index of the single layers has been measured and used to estimate absorber thermal efficiency at the operating temperatures. Multilayers have been produced via sputtering deposition on bulk copper substrates. The absorber multilayers can be 10% more efficient than the commercial alternative at 250 °C operating temperatures, reaching 380 °C stagnation temperature without Sun concentration. The thermal stability has been checked at temperature of 400 °C in vacuum for four hours. High vacuum flat thermal collectors, equipped with the produced selective solar absorbers can obtain unprecedented performances and can give important contribution to the energy transition from fossil fuels to renewable energy for efficient heat production.

The H2-ICE project aims at developing, through numerical simulation, a new generation of hybrid powertrains featuring a hydrogen fueled Internal Combustion Engine (ICE) suitable for 12-meter urban buses, in order to provide a reliable and cost-effective solution for the abatement of both CO2 and criteria pollutant emissions. The full exploitation of the potential of such a traction system requires a substantial enhancement of the state of the art since several issues have to be addressed. In particular, the choice of the more suitable fuel injection system, as well as the control of the combustion process, are extremely challenging. Firstly, a high-fidelity 3D-CFD model will be exploited to analyze the in-cylinder H2 fuel injection through supersonic flows. Then, after the optimization of the injection and combustion process, a 1D model of the whole engine system will be built and calibrated allowing the identification of a “sweet spot”, in the ultra-lean combustion region, characterized by extremely low NOx emissions and, at the same time, high combustion efficiencies. Moreover, to further enhance the engine efficiency well above 40 %, different Waste Heat Recovery (WHR) systems will be carefully scrutinized, including both Organic Rankine Cycle (ORC)-based recovery units as well as electric turbo-compounding. A Selective Catalytic Reduction (SCR) aftertreatment system will be developed to further reduce NOx emissions to near-zero levels. Finally, a dedicated torque-based control strategy for the ICE coupled with the Energy Management Systems (EMS) of the hybrid powertrain, both optimized by exploiting Vehicle-To-Everything (V2X) connection, allow targeting an H2 consumption of 0.1 kg/km. Technologies developed in the H2-ICE project will enhance the know-how necessary to design and build engines and after-treatment systems for the efficient exploitation of H2 as a fuel, as well as for their integration into hybrid powertrains.

The objective of this study was to analyze the epidemiological links of HIV, HCV and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15-87 years who took part in the Open Test Project. They were divided into two subgroups: general population and individuals from prisons, and questioned about multiple risk factors. Chi-Square Independence Test was used to establish correlations between the risk factors and the results of the screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug use (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with injecting drug use (the strongest association), unprotected sexual intercourse with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.

Depressive disorders represent the leading contributors to mental health-related global burden, and they are often diagnosed in the context of many comorbid disorders, such as cardiovascular disorders, Stroke, Parkinson’s Disease, Major Neurocognitive Disorders and Headache, thus worsening their outcomes. Depression is a challenge for “real-world” clinicians, due to the low rates of remission despite the increasing number of antidepressant strategies currently available. Indeed, current antidepressant strategies often fail to achieve acceptable rates of remission. One of the main challenges of “real-world” management of depression is represented by geriatric depression, which is common and under diagnosed. The challenge of diagnosis and treatment of geriatric depression in real world calls for the need of a deeper exploration of its management in clinical practice. This is the purpose of the present cross-sectional survey, aimed at evaluating the clinical approach to late-life depression in a sample of expert physicians working in geriatric settings in Italy, thus trying to provide useful insights on geriatric depression care.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

Among solar thermal collectors, the evacuated flat panel is emerging as a reference technology for operation at higher temperatures of up to 200 °C with an increased annual energy production owing to both direct and diffuse light capture. Accurate measurements of the optical properties of the selective absorbers used in such devices are key for a reliable estimation of the overall performance. These optical properties must be measured under high vacuum at high temperatures, conditions under which the panels are meant to operate. In this study, we accurately measured these properties using a calorimetric technique. The measurement procedure is based on a power balance equation for a flat sample suspended in a high-vacuum chamber with minimal thermal losses and is well adapted for this class of devices. Calorimetric measurements obtained under Sun and LED light revealed excellent reproducibility and good agreement with those obtained using traditional optical analysis at low temperatures in air. When extended up to the absorber stagnation temperature, which often exceeds 300 °C, the calorimetric measurements started to deviate from the optical measurements, indicating the importance of measuring under the operating conditions.

Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients - obs-AMI and MINOCA - NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI, a larger LVEDV and a lower LVEF compared to normoglycemic ones. Conversely, MINOCA patients showed similar myocardial damage, irrespective of glycemia. Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative such as Escherichia coli and Salmonella enterica serovar Typhimurium. Grape seeds, wine industry by-products, have antioxidant, antimicrobial, and anti-inflammatory activities. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damages has been studied in a model of Caco-2 cells. The in vitro activity of prGSE against formation of biofilm of S. Typhimurium and E. coli, has been investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results showed that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by LPS treatment of Caco-2 cells has been demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In in vivo activity, increased survival of infected G. mellonella larvae after treatment with prGSE has been demonstrated. In conclusion, grape seed extracts could be used in the reduction of GI damage caused by bacterial endotoxin and biofilm of Gram-negative bacteria.

Objectives: This study assessed the performance of a novel fluoride dentifrice containing micro- fibrillated cellulose (MFC) and 7% silica (Protegera™) versus common fluoride dentifrices. Methods: Removal of extrinsic stains was assessed using the pellicle cleaning ratio (PCR) method, and radioactive dentin abrasivity (RDA) was measured, to calculate a cleaning efficiency index (CEI). Fluoride efficacy was evaluated using widely used remineralization and fluoride uptake methods. Results: The MFC dentifrice removed stained pellicle significantly more effectively than the ADA reference material, Crest Cavity Protection™ and Sensodyne Pronamel™, and had equal performance to three known marketed stain-removing dentifrices (Arm & Hammer™ Advanced Whitening, Crest ProHealth™, and Colgate Optic White™). The MFC dentifrice vehicle had a low RDA (88), which was significantly less than Crest ProHealth (166) and Crest 3D-White™ (183). Based on PCR and RDA data, the CEI was 31% greater for the MFC product than for Crest ProHealth. In a 10-day pH cycling study, the fluoride efficacy of the MFC product was superior to a non-fluoridated control and was not significantly different from Sensodyne Pronamel and Crest Cavity Protection. The MFC dentifrice was superior for promoting fluoride uptake into incipient enamel lesions than the USP reference dentifrice. Conclusion: The low dentin abrasivity MFC dentifrice is highly effective in removing stained pellicle, and is an efficacious fluoride source when compared to other relevant commercially available fluoride dentifrices with high dentin abrasivity. Clinical Significance: Including micro-fibrillated cellulose into a fluoride dentifrice may enhance cleaning performance for the removal of external stain, while lowering abrasivity, and providing an effective fluoride source. This combination of benefits seems well suited to enamel protection and caries prevention.

In patients with prior Takotsubo syndrome (TTS), long lasting functional cardiac limitations were described as compared with normal subjects. Emotions-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable fac-tors. The aim of the present study was to assess long-term cardiac functional limitations in a co-hort of asymptomatic E-TTS patients. We enrolled n=39 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 [12-40] months median fol-low-up from the acute event. A cohort of n=39 individuals matched for age, sex, body mass index and comorbidities served as control. Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs 22.5 ± 6.5; P < 0.001 and 75.2 ± 14.1 % vs 100.6 ± 17.1%, P <0.001), VO2 at anaerobic threshold (AT) (11.1 [10.1-12.9] vs 14.4 [12.5-18.7]; P <0.001), peak O2 pulse (9.7 ± 2.5 vs 13.1 ± 3.5; P <0.001) and higher VE/VCO2 slope (30.4 ± 3.7 vs 27.2 ± 3.5; P <0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Despite its favorable out-come, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

The fabrication of thin-film multilayer structures by sputtering technique usually requires multi-cathode deposition machine. This study proposes a simpler approach based on the RF power modulation: silicon nitride (SiN$_x$) thin films were prepared by RF reactive sputtering in (Ar + N$_2$) atmosphere at room temperature. The samples were analyzed to highlight the effects of different deposition conditions on the morphological and optical properties of the films in the visible and near/mid-IR regions. The refractive index of the films was changed in the range of 1.5 - 2.5 (at $\lambda$=800 nm) by tuning the sputtering power. IR reflectance measurements revealed the absence of spurious (oxygen- or hydrogen-based) phases, while atomic force and scanning electron microscopies confirmed the presence of flat and defect-free samples surfaces.

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful in discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NET), calprotectin, DNase plasma levels by ELISA, and a panel of pro-inflammatory cytokines by ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and more in hospitalized than non-hospitalized ones. C5a and sC5b-9, and other acute phase proteins correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NET, and neopterin are important proinflammatory parameters potentially useful in discriminating between COVID-19 patients at risk for hospitalization.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

Next generation sequencing (NGS) from SARS-CoV-2-positive swabs collected during the last months of 2022 revealed a large deletion between ORF7b and ORF8 (426 nt) in six patients infected with the BA.5.1 Omicron variant. This extensive genome loss removed a large part of these two genes, maintaining in frame the first 22 aminoacids of ORF7b and the last 3 aminoacids of ORF8. Interestingly, the deleted region was flanked by 2 small repeats, likely involved in the formation of a hairpin structure. Similar rearrangements, comparable in size and location to the deletion, were also identified in 15 sequences in the NCBI database. In this group, 7 out of 15 cases from the USA and Switzerland presented both the BA.5.1 variant and the same 426 nuclotides deletion. It is noteworthy that 3 out of 6 cases were detected in patients with immunodeficiency and is conceivable that this clinical condition could promote the replication and selection of these mutations.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

Uniform illumination is a key requirement in different research fields. However, this requirement is often difficult to achieve when high intensity is required at the same time. Recent advancements in LED lamps allow nowadays for compact and economical solutions. In this work we present a suitable solution for various laboratory purposes requiring stable, uniform and high intensity illumination. The system is composed of four identical high power white LED arrays of 30 mm diameter each, placed on a supporting and cooling structure having a minimum volume of 26 cm x 26 cm x 8 cm. A numerical model has been developed, based on a ray tracing software, in order to simulate the performances. These have then been experimentally validated with measurements of the power density map, carried out with a 1% uncertainty pyranometer. Data show that the built system is very stable over time and provides an illumination uniformity higher than 98%, on a surface of 50 mm radius, which reduces to 95% on a surface of 75 mm radius. The power density can be adjusted in the 390-1360 W m-2 range, not affecting uniformity.

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring SARS-CoV-2 prevalence in a city in Northern Italy from October 2021 to May 2023. Starting from a widely applied deterministic model, this study proposed a variation to take into account population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated with healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred in the considered period, demonstrating the model’s capacity to predict relevant fluctuations in the number of cases. Population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied for comparing virus load values across cities with varying population demographics and sewer network structures, enhancing the comparability of WBE data for effective surveillance and intervention strategies.

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non- canonical latency program of EBV with an activated PD-L1 pathway. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

Background Very few cases of Pneumocystis jirovecii pneumonia (PCP) have been reported in COVID-19 so far, mostly in patients with concomitant HIV infection or in solid organ transplant recipients. Despite COVID-19 is associated with lymphopenia and use of steroids, there are no studies specifically aimed to investigate risk factors for PCP in COVID-19 Methods retrospective case-control study in a cohort of patients with confirmed COVID-19. Direct immunofluorescence assay on respiratory samples was used to diagnose PCP. Results We enrolled 54 patients. Patients with PCP had significant lower median lymphocyte values (p=0.033), longer COVID-19 disease duration (p=0.014), higher cumulative dose of steroid received (p=0.026), higher CRP values (p=0.005) and lower SARS-CoV-2 vaccination rate than controls (p=0.029). Cumulative steroid dose (p=0.042) and the highest CRP value during the stay (p=0.012) were identified as risk factor for PCP, while SARS-CoV-2 vaccination with one (p=0.029) and two doses (p=0.049) as a protective factor for PCP, although not independently associated. Conclusions PCP develops in COVID-19 patients regardless of immunosuppressive conditions. However, a higher rate of PCP is significantly associated with the cumulative steroidal dose, high CRP values and lack of vaccination.

Background: Sepsis still represents a major public health issue worldwide, and immune system plays a main role during infections and therefore its activity is mandatory to resolve this clinical condition In this report we aimed to retrospectively verify in real life setting the possible usefulness of Pentameric IgM plus antibiotic in recovering patients with sepsis after major abdominal surgery Materials/methods: We reviewed, from January 2013 until December 2018, all adult patients admitted in ICU for Sepsis or Septic shock (2) after major abdominal surgery. Among these patients, were identified those that according to legal indication and licence in Italy, were treated with Pentameric IgM plus antibiotic (Group A) or with antibiotic alone (Group B). We analysed the following parameters were evaluated: Blood gas analysis, Lactate, CRP, Procalcitonin, Endotoxin activity, Liver and Renal Function, Coagulation, Blood Cell count at different time points (Every 48 hrs for at least 7 days. Differences between groups have been analysed by Fisher’s exact test or Chi square test for categorical variables. Mann–Whitney U test or Kruskal–Wallis test have instead been performed to compare continuous variables. Univariate and Multivariate analysis were also performed Results: Over a period of 30 months 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects no statistical differences have been found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or in inflammatory index, SOFA score, lactate levels and mortality rate. A 48hrs response was statistically more frequent in Group B than in Group A, while no differences were found in the other clinical and laboratory evaluation. Conclusions: Based on our results, the use of pentameric IgM do not seem to give any clinical advantage in sepsis after to major abdominal surgery.

Background: Malnutrition is a frequent condition in the elderly and is associated with prolonged hospitalization and increased mortality. However, the impact of malnutrition among elderly patients with acute myocardial infarction has not been clarified yet. Methods and Results: We have enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI) who underwent to the evaluation of nutritional status by Mini Nutritional Assessment (MNA) and of mortality risk by Grace score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 ± 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse GFR, lower SBP, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that Grace score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95% CI = 1.34–2.32 and HR = 0.56, 95% CI = 0.42–0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included compared to the partial models without MNA. Conclusions: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with/at risk of malnutrition in order to apply interventions to improve nutritional status and maybe survival in this population.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. Neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. This systematic review provides an overview on the value of NfL in early detection of neuropathy, central nervous system involvement, monitoring of neuropathy progression, and treatment effect in systemic amyloidosis. A literature search in PubMed, Embase and Web of Science was performed on 14-02-2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene variant (TTRv) carriers. Only studies containing original data were included. Included were twelve full-text articles and six abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has potential to be used for early detection of neuropathy, monitoring treatment effect, and monitoring disease progression in patients with systemic amyloidosis.

Background: Hepatic interstitial T-lymphocytes (T-Li), Natural Killer (NK) and NK-T cells play an important role in both innate and adaptive immunity and contribute to the regulation of ischemia/reperfusion injury (IRI) after transplantation of abdominal organ. Methods: The cellular concentrations and phenotypes of NK, T-Li, NK-T were analyzed retrospectively in a consecutive series of hepatic perfusates after surgical removal of whole livers on the bench previously collected from adult multi-organ donors after brain death. (DBD), and compared with the demographic and pathological characteristics of the patients transplanted at our Institute with kidneys taken from the same donors. The liver interstitial cells were purified from the perfusate by density gradient centrifugation and the phenotype was determined by flow cytometric investigation using the following immunological markers: CD3, CD4, CD8 and CD56 in order to determine the relative percentage of T-Li, NK-T and NK cells. Results: The perfusates of 42 DBDs, and the related clinical outcome of kidney transplant recipients from 2010 to 2020, were analyzed. T-Li were significantly associated with the time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02), to onset of secondary infection from Cytomegalovirus (p = 0.03). On COX analysis, percent cell concentration of T-Li and time to DGF were significantly associated with an increased relative risk (HR) of organ survival (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). The specificity of the NK and NK-T cell proportions were not associated with any relevant clinical outcomes in kidney transplant patients. Conclusions: The present study points to a new potential role of T-Li cells detected in the context of liver perfusate DBD, and could detect potential impacts in organ allocation, surgical harvesting techniques and in the analysis of IRI pathophysiological events after kidney transplants from multi-organ DBDs.