Mothers’ own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for the effects on the outcome in the short and long term, especially the neurological one. We studied the use of the MOM for WLBWs over a 5-year period. Statistical comparisons concerned data on feeding with the MOM during stay in NICU and at discharge with respect to maternal and neonatal variables (gestational age, birth weight, type of pregnancy if single or twin, maternal age) and to feeding data (timing of the start of the Minimal Enteral Feeding and the availability of the MOM, the achievement of the Full Enteral Feeding, the type of nutrition at discharge). We observed an increase, between 2017 and 2021, of MOM use (p=0.003). The availability of the MOM occurred on average on the fourth day of life and improved over the years. Start of MEF with human milk averaged 1.78 days and 54.3% of VLBWs received MEF with donor milk on the first day of life (50% within the first 6 hours). The average MOM at discharge was 47.6% with 36.1% exclusive MOM (EMOM) and an increase from 45.8% in 2017 (EMOM 33.3%) to 58.82% (EMOM 41.18%) in 2021. The mean average daily growth of the weight improved (p<0.001) during this period. There is no statistical difference between infants fed with MOM and those fed with bank milk. The maternal age, the start day of the MOM feeding and gestational age have a significant impact on the type of feeding at discharge.

We are witnessing the revival of the CAM model, which was already used in the past by some authors studying angiogenesis and anti-cancer drugs, that now offers a refined model to fill, in the translational meaning, the gap between in vitro-in vivo studies. It can be used for a wide range of purposes, from testing cytotoxicity, pharmacokinetics, tumorigenesis, invasion, to action mechanisms of molecules, and validation of new materials from tissue engineering research. CAM model is easy to use with a fast outcome and makes experimental research more sustainable since allowing to replace, reduce and refine pre-clinical experimentation ("3Rs" rules [1]). This re-view aims to highlight some unique potentials that CAM-assay presents; in particular, the authors intend to use in the next future the CAM model to verify, in a microenvironment comparable to in vivo conditions, albeit simplified, the angiogenic ability of functionalized 3D constructs to be used in regenerative medicine strategies in the recovery of skeletal injuries of critical size (CSD) that do not repair spontaneously. For this purpose, organotypic cultures will be planned on sever-al CAMs set up in temporal sequence: a sort of organ model for assessing CSD conducted in the CAM bioreactor, rather than in vivo.

Chicory, a horticultural crop cultivated worldwide, presents many botanical varieties and local biotypes. Among these, Italian radicchio group cultivars of pure Cichorium intybus L. and interspecific hybrids with Cichorium endivia L., as the “Red of Chioggia” biotype which in turn includes several phenotypes. This study deals with a pipeline for the marker-assisted breeding of F1 hybrids: it presents the genotyping-by-sequencing results of four elite inbred lines using a RADseq approach and an original molecular assay based on CAPS markers for screening mutants with nuclear male-sterility in radicchio of Chioggia. Two thousand nine hundred fifty-three SNP-carrying RADtags were identified and used to compute the actual estimates of homozygosity, and overall genetic similarity and uniformity of the populations, as well as to determine their genetic distinctiveness and differentiation. Molecular data were further used to investigate the genomic distribution of the RADtags among the two Cichorium species, allowing their mapping in 1,131 and 1,071 coding sequences in chicory and endive, respectively. In parallel, an assay to screen the genotype at the male-sterility locus Cims-1 was developed to discriminate wild-type and mutant alleles of the causative gene myb80-like. Moreover, a RADtag mapped close to this genomic region proved the potential application of this method for future marker-assisted selection tools. Finally, combining the genotype information of the core collection, the best ten individuals from each inbred line were selected to compute the observed genetic similarity as a measure of uniformity as well as the expected homozygosity and heterozygosity estimates scorable by the putative progenies derived from selfing (pollen parent) and full-sibling (seed parent) or pair-wise crossing (F1 hybrids). This predictive approach was conducted as a pilot study for understanding the potential application of RADseq in improving molecular breeding strategies aimed at the development of inbred lines and F1 hybrids in leaf chicory.

Food waste is one of the greatest challenge to sustainability in developed and developing countries. In the former, food waste is concentrated in the final part of the chain. Too Good To Go is a digital platform aimed to prevent food waste, where consumers can buy magic boxes from different outlets containing food products that are approaching their end-of-life. However, the mechanism of the platform enable the outlets to publish their offering much in advance of the pick-up time, raising the question whether the food sold on the platform is effectively a leftover or a planned production. Our empirical study gathers data from over 1200 outlets in Rome on the Too Good To Go platform.

In the context of precision agriculture (PA), geomatic surveys exploiting UAV platforms allow the trees’ dimensional characterization and crown identification. This paper focuses on the use of low-cost UAV photogrammetry to estimate the trees’ height, as part of a project for the phytoremediation of contaminated soils. Two study areas (Area 1; Area 2) have been chosen, having different characteristics in terms of mean trees’ height (5 m; 0.7 m), to test the procedure even in a challenging context. Three campaigns have been performed in Area 1 at different altitudes (30 m, 40 m, 50 m), and one UAV flight is available in Area 2 (42 m of altitude). The implemented workflow involves the elaboration of the UAV point clouds and DSMs using the standard SfM approach, the vegetation filtering, the generation of the DTM and a GIS-based analysis to obtain the CHMs for the extraction of the trees’ heights based on a local maxima approach. UAV-derived heights have been compared with in-field measurements obtaining promising results in Area 1, confirming the applicability of the procedure for trees’ height extraction, while the application in the context of low trees was more problematic.

Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 7 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. We focused on articles hypothesizing the identification and study of compounds that induce proliferation and osteogenic differentiation of the two d-DSC populations, representing an interesting issue for regenerative medicine. The reconstruction of bone defects in fact is still a challenge for personalized medicine.

Wild rocket plants were cultivated in a plastic greenhouse into two independent sectors, one for soil-bound (SbS) cultivation and another equipped for soilless (ScS) cultivation systems. In both SbS and ScS, the crop was subjected to treatments consisting in a high-compared to a low-input fertilization program (HF and LF treatment, respectively). Water use efficiency (WUE) and partial factor productivity (PFP) for nutrients (N, P, K, Ca and Mg for ScS, and N for SbS) were measured. Rocket leaves, separated for cultivation system and fertilization program, collected at different cuts during the growing cycle, were cold stored at 10 °C until 16 d. At each sampling day (at harvest and during the storage), sensory parameters, respiration rate, dry matter, colour, electrolyte leakage, antioxidant activity, total phenols, total chlorophyll and ammonia content were evaluated. In ScS, the PFP for all nutrients supplied as fertilizers showed a significant increase with the LF treatment, with values higher than 30 % for N, K and Ca. As for the postharvest performance, rocket leaves cultivated in ScS showed better qualitative traits than those cultivated in SbS, as suggested by the lower values of ammonia content and electrolyte leakage recorded at the end of storage in samples grown in ScS. Moreover, in ScS, data showed a lower membrane damage in LF than HF rocket leaves. Finally, regarding total chlorophyll content, even if no effect of treatments was recorded in SbS, rocket cultivated in ScS, showed a better retention of this parameter applying LF than HF treatment. In addition to this, a PLS model (R2 = 0.7) able to predict the cultivation system, using as variables total chlorophyll content no-destructively measured, was implemented.

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anticancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM, for 24/48 hours. We performed immunofluorescence experiments by means of confocal microscopy and Western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by flow cytometry assay to detect the cell apoptosis rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of nuclear factor E2–related factor 2 (NRF-2) and nuclear factor–kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing, since metformin is emerging as a multifaceted drug: it has a good safety profile and is associated with low cost, and it might be a promising candidate for the prevention or treatment of colorectal cancer.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein, and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a prote-ase promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphoryla-tion. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor, and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors.

The history of Artificial Intelligence (AI) development dates to the 40s. The researchers showed strong expectations until the 70s, when they began to encounter serious difficulties and investments were greatly, reduced. With the introduction of the Industry 4.0, one of the techniques adopted for AI implementation is Machine Learning (ML) that focuses on the machines ability to receive data series and learn on their own. Given the considerable importance of the subject, researchers have completed many studies on ML to ensure that machines are able to replace or relieve human tasks. This research aims to analyze, systematically, the literature on several aspects, including publication year, authors, scientific sector, country, institution, keywords. Analyzing existing literature on AI is a necessary stage to recommend policy on the matter. The analysis has been done using Web of Science and SCOPUS database. Furthermore, UCINET and NVivo 12 software have been used to complete them. Literature review on ML and AI empirical studies published in the last century was carried out to highlight the evolution of the topic before and after Industry 4.0 introduction, from 1999 to now. Eighty-two articles were reviewed and classified. A first interesting result is the greater number of works published by USA and the increasing interest after the birth of Industry 4.0.

This paper describes a case study for applying of hybrid-electric propulsion system for a general aviation aircraft. The work was performed by a joint team of CIRA and the Department of Industrial Engineering of the University of Naples “Federico II”. Electric and hybrid electric propulsion for aircraft has gained widespread and significant attention over the past decade. The driver for industry interest has principally been the need to reduce emissions of combustion engine exhaust products and noise, but increasingly studies revealed potential for overall improvement in energy efficiency and mission flexibility of new aircraft types. The project goal was to demonstrate feasibility of aeronautic parallel hybrid-electric propulsion for a Light aircraft varying the mission profiles and the electric configuration. Through a creation, and application, of a global model, with software AMESim^®, in which it can be represented everything about the components chosen by the industrial partners, some interesting considerations are carried out. In particular, it was confirmed that with the only integration of state of the art technologies, for some particular missions, the advantages of aircraft hybrid-electric propulsion, for light aircraft, are notable.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

An alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study (Am J Med. 2016 Dec; 129(12):1299-1306). However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs , as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs . The purpose of this retrospective study is to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients, aged over 70 years.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

MAD is the gold standard therapy for mild/moderate OSA and is a second-choice treatment in patients with severe OSA not responding to CPAP. The aim of this study was to analyze the upper airway characteristics of OSA patients and the morphological changes in the upper airway, inducted by four different types of mandibular advancement devices, using CBCT 3D imaging. Twenty-two patients were recruited after OSA diagnosis with polysomnography. Four different customized and titratable MAD were used and an initial CBCT scan was obtained for each patient. After 6 months to the end of the MAD titration phase, all the subjects showed an AHI of &lt; 5 or a decrease of 50% in AHI with MAD when compared with initial AHI and a second CBCT scan with MAD in situ was performed. An important improvement of the airway was observed (+33.76%) and a significant difference in the enlargement ratio between the posterior soft palate (+32.41%) and the posterior tongue (+36.96%) region was also found. The greatest increase in airway volume was achieved in patients treated with the MAD Forward and TAP (respectively +42.77% and + 41.63%). MAD therapy is effective to treat mild/severe OSA with increased upper airway volume. The design of the MAD can influence the effectiveness of the treatment.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Building Information Modelling (BIM) is increasingly adopted in supporting Facility Management (FM). However, in the future perspective of efficiently encouraging the management of building estates, e.g. owned by public authorities or institutions, providing an effective integration between Building Information Models and Geographic Information Systems (GIS) becomes also essential. This contribution is therefore aimed at presenting a methodological framework integrating BIM and GIS environments by mainly taking advantage of open-source tools (e.g. QGIS and Dynamo) and non-proprietary data exchange formats like the COBie (Construction-Operations Building Information Exchange) international standard. Unlike what has been mainly proposed in the literature concerning BIM-GIS integration so far, the methodology presented in this paper does not provide for an integral transfer of BIM data to the GIS platform. The work led instead to the development of an effective bidirectional integration between the two informative systems, by properly relating them and allowing for an easy switch from one system database to the other. This integrated framework is intended to enable facility managers to easily visualize in the GIS platform, through queryable 2D and 3D maps, some relevant information from BIM to efficiently manage workspaces. At the same time, this hybrid informative system allows BIM practitioners to access and manage more detailed information stored in Building Information Models. The findings of experimental applications of the proposed methodological approach to the ex-Macciotta pediatric hospital, a healthcare building owned by the University of Cagliari, are finally presented and discussed.

Since alternative methods (AAs), such as in vitro cultures, organs in silico, or mathematical methods, are not fully able to reproduce the complexity of the human organism, particularly neu-ral processes, and brain structures, animal experimentation remains the only way in which re-search can obtain the necessary knowledge to suggest drug therapies or targeted therapeutic in-terventions. Particularly in neuroscience, transgenic animals allow us to model neurological dis-eases, study the relationship between the brain and behavior, and decipher the function of genes involved in pathological conditions. However, it should never be forgotten that animals are "sen-tient beings" capable of feeling pleasure and pain (Art. 13 of the 2007 Lisbon Treaty). For this rea-son, it is crucial to prioritize the welfare of animals involved in testing by considering their phys-ical, psychological, adaptive, and relational well-being. This is where the concept of a Culture of Care comes in, where the responsibility of care extends beyond the veterinary aspects to include everything that can safeguard the welfare of animals before, during, and after experimentation. This chapter explains the advantages of using the animal model while practicing the culture of care in neuroscience, as both animals and research outcomes benefit from this approach.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

Nucleic acid therapeutics are witnessing an impressive acceleration in recent years. They work through multiple mechanisms of action, including downregulation of gene expression and modulation of RNA splicing. While several drugs based on the former mechanism have been approved, few target the latter, despite the promise of RNA splicing modulation. To improve our ability to discover novel RNA splicing-modulating therapies, we developed HCS-Splice, a robust cell-based High-Content Screening (HCS) assay. By implementing the use of a two-colour (GFP/RFP) fluorescent splicing reporter plasmid, we developed a versatile, effective, rapid, and robust high-throughput strategy for the identification of potent splicing-modulating molecules. The HCS-Splice strategy can also be used to functionally confirm splicing mutations in human genetic disorders or to screen drug candidates. As a proof-of-concept, we introduced a dementia-related splice-switching mutation in Microtubule-Associated Protein Tau (MAPT) exon 10 splicing reporter. We applied HCS-Splice to the wild-type and mutant reporters and measured the functional change in exon 10 inclusion. To demonstrate the applicability of the method to cell-based drug discovery, HCS-Splice was used to evaluate the efficacy of an exon 10-targeting siRNA, which was able to restore the correct alternative splicing balance.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Mandevilla (Apocynaceae) is a greatly appreciated genus in the world ornamental market. In this study, we attempted to address the poor genetic knowledge and the huge taxonomic gaps existing in this genus by analyzing the germplasm of 55 accessions. After cytometrically determining the triploid genome size (1,512.64 Mb) of a reference sample (variety “Mandevilla 2001”), the plastidial genome (cpDNA, 0,18 Mb) and a draft of the nuclear genome (nuDNA, 207 Mb) were assembled. While cpDNA was effective in reconstructing the phylogenesis of the Apocynaceae family based on a DNA superbarcoding approach, the nuDNA assembly length was found to be only 41% of the haploid genome size (506 Mb, predicted based on the K-mer frequency distribution). Its annotation enabled the prediction of thousands of genes, of which 5,275 resulted in full CDS. Among them, we identified nine genes whose orthologs (in Catharanthus roseus) encode enzymes involved in the biosynthesis of monoterpene indole alkaloids (MIAs), including catharanthine, tabersonine and vincadifformine. The nuclear genome draft was also useful to develop a highly informative (mean PIC=0.62) set of 23 SSR markers that was validated on the Mandevilla collection. These results were integrated with cytometric measurements, nuclear ITS1 haplotyping and chloroplast DNA barcoding analyses to assess the origin, divergence and relationships existing among the 55 accessions object of the study. As expected, based on the scarce information available in the literature, the scenario was extremely intricate. A reasonable hypothesis is that most of the accessions represent interspecific hybrids sharing the same species as maternal parent (i.e., Mandevilla sanderi).

Clinical trials often involve new substances characterized or developed for a specific pathology or class of pathologies. At other times, a clinical trial is observational; in other words, a known sub-stance has a range of effects on a given cohort of subjects. The types of trials are different and complex, and often, young clinical novice and the inexperienced researchers may struggle to evaluate how to proceed correctly. In this paper, we aim to create a mini-guide for beginners in clinical trials and provide elements for designing a clinical trial. Our intention is to highlight where to find the materials and how to adapt, even in the absence of sponsors, so that even the most inexperienced and under-resourced researcher can gain an understqanding of the complexi-ty of the process andaddress it appropriately. We do not claim to be exhaustive or cover all ele-ments, but rather, we aim to create a checklist. With this approach, starting discussioms about the experimental phases of the drug and concluding with the clinical trial, we aim to assist those facing this challenging "world."

The present work presents and discusses an analysis of the floor types of Villa of Diomedes (Pompeii archaeological park in the Campania region, Italy) both from architectural, archaeological, and structural point of view. In particular, the geometrical structural parameters of different floor types and the rules used by ancient builders to design them are investigated by means of interdisciplinary research. Link between structural-based assumptions, archival sources, geometric survey, in situ visual inspections and the archaeological information make it possible to define the geometrical structural parameters of eleven-barrel vaults, three wooden floors and three sloped wooden roofs (buried and collapsed during the Vesuvius eruption). A specific study of the barrel vaults is presented to investigate the relationships between the main vaults’ structural parameter. Furthermore, a comparison between the vaults’ dimensions obtained from surveys and those produced by the literature formulations from the 15th to the 20th centuries concerning masonry-vault designs is presented and discussed. These analyses carried out in the framework of Villa of Diomedes interdisciplinary project was very useful to interpret the fabrication of the Villa and to make a reconstruction of 3D model as it probably resulted to be the fateful year of 79 A.D.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

In this work, the capabilities of a novel miniaturized and portable MicroNIR spectrometer were investigated in order to propose a practical and intelligible test allowing the rapid and easy screening of cannabinoids in hemp flour. In order to develop a predictive model able to identify and simultaneously to quantify the residual amount of cannabinoids, specimens from flours commercially available on the markets were considered and spiked with increasing amount of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Cannabigerol (CBG). Partial Least Square-Discriminant Analysis (PLS-DA) and Partial Least Square regression (PLSr) were applied for the simultaneously detection and quantification of cannabinoids. Results demonstrated that MicroNIR/Chemometric platform is statistically able to identify the presence of CBD, THC and CBG in simulated samples containing cannabinoids from 0.001 to 0.1 %ww, with the accuracy and sensitivity of the reference official methods actually proposed. The method was checked against false positive and true positive response and results proved to be those required for confirmatory analyses; permitting to provide a fast and accurate method for the monitoring of cannabinoids in hemp flours.

Sol-gel route represents a valuable technique to obtain functional materials, in which organic and inorganic members are closely connected. Herein four hybrid materials, containing caffeic acid entrapped in a silica matrix at 5, 10, 15 and 20 wt%, were synthesized and characterized through FT-IR and UV-Vis spectroscopy. FT-IR analysis was also performed to evaluate the ability to induce the hydroxyapatite nucleation. Despite some structural changes occurred on the phenol molecular skeleton, hybrid materials showed scavenging properties vs DPPH and ABTS+ radicals, which was dependent on the tested dose and on the caffeic acid wt%. Finally, the SiO₂/caffeic acid materials have been proposed as valuable antibacterial agents against Escherichia coli and Enterococcus faecalis.

The advent of CRISPR/Cas9 technology has revolutionized genome editing, enabling the attainment of once-unimaginable goals. CRISPR/Cas's groundbreaking attributes lie in its simplicity, versatility, universality, and its independence from customized DNA-protein systems, erasing the need for specialized expertise and broadening its scope of applications. Beyond its editing prowess, the discovery of novel Cas-based systems has spawned an array of additional biotechnological tools, empowering both fundamental and applied research. Researchers have harnessed CRISPR/Cas for gene regulation, deepening insights into gene expression and epigenetic changes. Precisely targeting DNA or RNA sequences, CRISPR/Cas effectively identifies and counters pathogens. Furthermore, it aids in genome imaging and sequencing, revealing genome spatial organization and chromatin dynamics. The non-editing applications of CRISPR/Cas exhibit tremendous potential across diverse domains, including diagnostics, biotechnology, and fundamental research. This article reviews and critically evaluates the primary CRISPR/Cas-based tools developed for plants and animals, underlining their transformative impact.

Epidemiologic studies suggest an inverse correlation between coffee consumption and the occurrence of neurodegenerative diseases, but the role of caffeine and roasting degree are still matter of debate. The objective of this work was to evaluate the effects of caffeinated (light, medium, and dark roast) and decaffeinated instant coffee samples in acetylcholinesterase inhibition and antioxidant assays, as well as in animal models of Parkinson’s disease. Caffeinated coffees inhibited the acetylcholinesterase in much smaller concentrations than decaffeinated coffee. All coffee samples showed antioxidant capacity without relation with the caffeine content. Dopaminergic-like activity in the haloperidol-induced catalepsy test was observed with caffeinated coffee, but not in the decaffeinated sample. The medium roast coffee reduced the number of rotations of rats after methamphetamine administration on the 6-hydroxydopamine unilateral lesion of the medial forebrain bundle. However, the coffee treatment did not avoid the loss of dopaminergic neurons on substantia nigra pars compact and only the smallest dose of coffee was able to avoid the decrease of dopamine levels in the lesioned side of the striatum. Altogether, these results suggest that coffee exerts moderate pro-cholinergic and pro-dopaminergic effects and caffeine seems to be the main responsible for these effects.

The medical research field has been tremendously galvanized to improve the prediction of therapy efficacy by the revolution in artificial intelligence (AI). An earnest desire to find better ways to predict the effectiveness of therapy with the use of AI has propelled the evolution of new models in which it can become more applicable in clinical settings such as breast cancer detection. However, in some instances, the U.S. Food and Drug Administration was obliged to back some previously approved inaccurate models for AI-based prognostic models because they eventually produce inaccurate prognoses for specific patients who might be at risk of heart failure. In light of instances in which the medical research community has often evolved some unrealistic expectations regarding the advances in AI and its potential use for medical purposes, implementing standard procedures for AI-based cancer models is critical. Specifically, models would have to meet some general parameters for standardization, transparency of their logistic modules, and avoidance of algorithm biases. In this review, we summarize the current knowledge about AI-based prognostic methods and describe how they may be used in the future for predicting antibody-drug conjugate efficacy in cancer patients. We also summarize findings of recent late-phase clinical trials using these conjugates for cancer therapy.

The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Background: Idiopathic normal pressure hydrocephalus is a syndrome with neuroradiological findings and clinical pattern characteristic but not specific for the pathology. Since the prevalence is growing due to the rapidly aging society, standardized and validated protocol for diagnosis is needed, also because this condition may mimic other disorders among elderly such as Parkinson's and Alzheimer's disease. Material and methods: We analysed data from 44 patients with suspect diagnosis of idiopathic normal pressure hydrocephalus with age > 60 years, clinical triad and neuroradiological pattern examined in our ward from November 2018 to November 2022. Neu-ropsychological assessment includes Mini Mental State Examination and Mental Deterioration Battery. Motor scores were collected from gait and balance tests. The evaluation was performed before and after an extended lumbar drainage last 48h. Patients who has scores improvement after the extended lumbar drainage, undergo ventriculoperitoneal shunt with a programmable valve. Results: All patients undergo neuropsychological assessment and motor tests, only 2 patients were unable to perform motor tests because bedridden. 16 patients showed no benefit from the tests, in 2 cases even a worsening of cognitive performance. 28 patients showed an improvement in their performances, but in most cases the improvement involved only the neuropsychological as-sessment. All patients underwent ventriculoperitoneal shunt have had a typical answers pattern in Mental Deterioration Battery test. We performed 9 ventriculoperitoneal shunt and 1 ventricu-lo-atrial shunt. Conclusions: Qualitative neurocognitive tests come out to be more sensitive compared to quantitative neurocognitive tests in identifying patients with suspected idiopathic normal pressure hydrocephalus benefiting from extended lumbar drainage test and then un-derwent surgical treatment. This could be considered a valid screening in elderly patients with suspected idiopathic normal pressure hydrocephalus in order to minimize the number of invasive procedures. More studies are necessary to validate this tool.

The purpose of this study was to evaluate the morpho-functional change of the patellar ligament in dogs affected by cranial cruciate ligament rupture. The hypothesis is that it may show increased thickening and stiffness with increasing days from trauma to diagnosis. Understanding this aspect have implications on the choice of timing to treat patients suffering from cranial cruciate ligament rupture, and also in the contextualization of patellar ligament desmitis pictures after surgical treatment with tibial plateau levelling osteotomy or tibial tuberosity advanced. Thirty-three dogs were affected affected by unilateral cranial cruciate rupture were examined and divided into three groups based on the time elapsed from the onset of lameness to diagnosis: Group 1 (from 1 to 15 days), Group 2 (from 16 to 60 days), Group 3 (over 60 days). Conventional B-mode ultrasonographic and elastosonographic examinations of patellar ligament were performed without sedation for each dog. At the ultrasonographic examination, all dogs showed alterations in the echostructure of the patellar ligament. In addition, the patellar ligament tended to become harder and less soft with increasing days after rupture, although there were not significant differences between groups. Our results showed that as time increases between the onset of cranial cruciate ligament rupture and diagnosis and treatment, the patellar ligament progressively thickens and loses its elasticity.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

The presence of azo dyes in textile effluents is an issue of major concern due to their potential impact on the environment and human health. In this study we investigate the photocatalytic degradation under visible light of Reactive Violet 5 (RV5), an azo dye widely used in the textile industry. A preliminary screening of different titania-based catalysts was carried out to identify the best candidate for RV5 removal. The selected catalyst was then tested in a stirred and aerated lab-scale reactor illuminated with a light LED source (λmax = 460 nm). The effects of pH, catalyst load and hydrogen peroxide additions on the efficiency of dye removal were evaluated. Under the best conditions (pH 10, 3 g/L of catalyst and 60 mM hydrogen peroxide), the dye solution was completely decolorized in about 2 h. Overall, the results obtained suggest that the proposed process may represent a suitable method for the removal of RV5 from textile effluents.

The aim of this work is to propose two different and complementary sensors for the structural health monitoring of concrete beams. In particular, a diffused sensing element and a split ring resonator network are presented. The first sensor is able to detect the variation of the dielectric properties of the concrete along the whole beam length, for a diffuse monitoring both during the important concrete curing phase and also for the entire life cycle of the concrete beams. The resonators instead work punctually, in their surroundings, allowing an accurate evaluation of the permittivity both during the drying phase and after. This allows the continuous monitoring of any presence of water both inside the concrete beam and in points that can be critical, in the case of beams in dams, bridges or in any case subject to a strong presence of water which could lead to deterioration, or worse, cause serious accidents. Moreover, the punctual sensors are able to detect the presence of cracks in the structure and to localize them.

The size of TiO2 (either nanometric or micrometric) can significantly affect both its photocatalytic and photoelectrochemical properties, thus altering the photooxidation of organic pollutants in air or water. The purpose of this work is to give an account of the photoelectrochemical and photocatalytic features of some nano- and micro-sized TiO2 commercial powders towards a model reaction, the photooxidation of acetone. Cyclic voltammograms (CV) of TiO2 particulated electrodes under UV illumination experiments were carried out in either saturated O2 or N2 solutions for a direct correlation with the photocatalytic process. In addition, the effect of different reaction conditions on the photocatalytic efficiency under UV light in both aqueous and gaseous phases was also investigated. CV curves with the addition of acetone under UV light showed a negative shift of the photocurrent onset, confirming the efficient transfer of photoproduced reactive oxygen species (ROSs), e.g., hydroxyl radicals, or holes to acetone molecules. The photocatalytic experiments showed that the two nano-sized samples exhibit the best photocatalytic performance. The different photoactivity of the micro-sized samples is probably attributed to their morphological differences, affecting both the amount and distribution of free ROSs involved in the photooxidation reaction.

Crops obtained by genome editing (GE) technologies represent a notable and disruptive shift from genetically modified or transgenic plants, outpacing public perception and regulatory frame-works. Multiple aspects of GE are contributing to the advancement of modern agriculture, in-fluencing the market structure by introducing specific changes within the existing genetic blue-print of an organism. Generally, the GE toolbox includes distinct technologies able to incorporate site-specific and pre-determined genomic modifications, exploiting well-established genetic modification strategies. For these reasons, GE-derived approaches are considered new plant breeding methods, known as new breeding techniques (NBTs). Particularly, CRISPR/Cas-based technologies represent a considerable improvement over prior techniques, being more precise, accurate and straightforward for targeted gene editing, in a reliable and reproducible way, with numerous applications. CRISPR/Cas system exploitation for non-editing purposes has also been widely documented, ranging from cell imaging to expression regulation and DNA assembly. Recently, CRISPR/Cas systems have been employed for target detection and could be used to ef-ficiently identify multiple organic chemicals. High-sensitivity and high-specificity detection are two main points of the CRISPR/Cas technology, without needing complex expertise or technical pipelines. This manuscript aims to provide an overview of the main advances of CRISPR/Cas-based systems into new frontiers of non-editing. The associated implications (e.g., molecular traceability) and their relative impacts are also presented and discussed.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, re-considering the immunohistochemical negative score of 0, 1+ or score of 2+/in situ hybridization (ISH) negative phenotype. In the present review we have outlined the needed criteria to exactly distinguish HER2 low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these group sof tumors. In particular, Trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC has been recently approved by the U.S. Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally we hope that new guidelines may help to codify HER2 low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.

Grape dehydration is practiced widely in the food industry with large yields of sultanas produced globally. This paper proposes an investigation into grape microstructure changes as it is dried by imaging specimens at intervals during dehydration at two temperatures using scanning electron microscopy. Detailed images of the microstructure were obtained, and a unique image processing algorithm was developed to quantitatively analyse the properties of this microstructure. Two main methods were developed to obtain the complex boundaries of cells present in the grape tissue in over 36 SEM images. Segmentation of the binary image using an adapted watershed function obtained the most consistent and accurate morphological shape. This was compared to a secondary method which used Canny’s edge detection function, morphological closing and skeletonizing to outlines the cellular microstructure. MATLAB was utilised to convert these boundaries into measurable areas so that quantitative data on average cell area, perimeter and cell axis lengths was acquired. It was found that over drying time cell area and perimeter reduced as expected. Some variability in the data was clear due to only single samples being analysed for each temperature and time combination. The development of automatic image processing techniques will enable quantitative data to be extracted from these images. Trends in cell perimeter, diameter and shape will be used to demonstrate relationships between morphological structure, drying temperature, and duration.

Cardiovascular disease (CVD) is a major global health concern. The number of people with CVD is expected to rise due to aging populations and increasing risk factors such as obesity and diabetes. Identifying new molecular markers is crucial for early diagnosis and treatment. Among these, plasma levels of some miRNAs specifically expressed in cardiac and skeletal muscle known as myomiRs, has gained attention for their roles in cardiovascular health. This study analyzed the plasma levels of myomiR-133a, -133b, and -206 in the pathogenesis of cardiovascular diseases. Exploiting of a case-control study design with patients recruited from several nursing homes form Calabria (Southern Italy) characterized by different types of CVD compared to non-CVD controls, we found downregulation of miR-133a in heart failure and miR-133b in stroke, along with the overall decreased expression of miR-133b and miR-206 in CVD patients. In silico functional characterization of their targets and signaling pathways revealed their involvement in critical cardiovascular processes. Although further research is necessary to fully elucidate their mechanisms and clinical utility, the results here reported support the idea that myomiRs could serve not only as biomarkers but also as therapeutic targets, offering new avenues for managing and potentially preventing CVD progression.

Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.

A Pediatric Sleep Questionnaire (PSQ) and a recording of the respiratory parameters with a noc-turnal home cardiorespiratory polygraphy (PG) are necessary to diagnose OSAS. Few researchers have studied how obesity could influence the respiratory parameters in OSAS children. The aim of the study was to investigate how obesity can influence sleep respiratory parameters in OSAS children. Methods: The study analyzes 56 Caucasian children and adolescents aged 11 ± 2.79 years with a BMI> 5th percentiles and PSQ value of 0.33. Children were divided into the Obesity Group (OG) with a BMI of  95th and the Control Group (CG) with a 5th<BMI> 95th percentile. All selected children underwent PG. Respiratory parameters were extracted to divide into levels of severity OSAS: snoring, mild, moderate, and severe. Results: The comparison analysis of AHI, SaO2, and Nadir between the OG and CG showed a statistical significance only for ODI (p = 0.02). The comparison analysis of PSQ between the OG and CG and of PSQ and respiratory parameters showed no significant result. A statistically significant correlation between BMI and AHI (r2=0.01), SaO2 (r2=0.09), and Nadir O2 (r2=0.00) was found. Conclusion: There was no strong correlation between Obesity and OSAS, but it was found between BMI increasing and AHI severity

This study aimed to characterize the genetic subtypes of HCV-GT4 and identify the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT4 patients was analyzed. Sequence analysis of NS3, NS5A and NS5B regions was performed by direct sequencing. In addition, phylogenetic analysis was used to determine genetic subtypes, RAS and polymorphisms. Nine patients were infected by a GT4a, one with GT4o, 3 with GT4d. The remaining four patients were infected with a recombinant virus (GT4a+GT4o in three patients, GT4c+GT4d in a patient). Natural RASs were found in six patients (35%), including three infected by GT4a, two by GT4a+GT4o and one patient infected by GT4c+GT4d. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M+M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about a third of patients, but only one of them showed a treatment failure.

Given the opportunities offered by foreign investment in energy infrastructure mostly by Chinese firms, the Government of Cambodia is giving high priority to developing hydropower resources for reducing energy poverty and powering economic growth. Using a “Political ecology of the Asian drivers” framework, this paper assesses China’s involvement in the development of large dams’ in Cambodia and its impacts on the access of natural resources such as water and energy by dam builders, local communities and the government. This analysis is based on 61 interviews and 10 focus group discussions with affected communities, institutional actors, Chinese dam builders and financiers in relation to the first large Chinese dam built in Cambodia, the Kamchay dam. Based on the results of the analysis this paper makes recommendations on how to improve the planning, implementation and governance of large dams to ensure that the dams’ benefits are shared more equally.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

Virgin coconut oil (VCO) is a functional food with important health benefits. Its economic interest encourages fraudsters to deliberately adulterate VCO with cheap and low-quality vegetable oils for financial gain, causing health and safety problems for consumers. In this context, there is an urgent need for rapid, accurate and precise analytical techniques to detect VCO adulteration. In this study, the use of Fourier Transform Infrared (FTIR) spectroscopy combined with Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) methodology was evaluated to verify purity or adulteration of VCO with reference to several low-cost commercial oils such as sun-flower, maize and peanut oils. Control charts were developed to assess the purity of oil samples using MCR-ALS scores values calculated from a data set of pure and adulterated oils. In addition, quantification models were developed using MCR-ALS with correlation constraint for adulterated coconut oil to assess the blend composition. Different data pre-treatment strategies were tested in order to best extract the information contained in the sample fingerprints, and the calibration models were optimised using a genetic algorithm (GA) to select the most important variables. The models gave satisfactory results in external validation procedure, with absolute errors of less than 4.6 % for samples adulterated with sunflower, maize and peanut oils.

Bisphosphonates (BPs) are successfully used to cure a number of bone diseases characterized by metabolic osteopenia, such as Osteoporosis, or neoplastic osteolysis, such as Multiple Myeloma and Bone Metastases. These drugs exert their therapeutic effect inducing a systemic osteoclast depletion that, in turn, is responsible for a reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as Osteonecrosis of the Jaw (ONJ). It is generally believed that the inability of osteoclasts to get rid of inflamed / necrotic bone tissue represents the main physio-pathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. We have previously demonstrated that Magnesium (Mg) is a powerful inducer of osteoclast differentiation. Using a model of Vitamin D3 – dependent osteoclastogenesis, based on the U937 cell line, here we show that, surprisingly, this property of Mg is greatly enhanced by the presence of Zoledronic Acid (ZA), chosen for our study because it is the most effective among BPs. This finding allow us to hypothesize that Mg might play an important role in the topical therapy of ONJ.

Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs has a strong prognostic role in triple negative breast cancer (TNBC). Little is known about his interaction with Androgen receptor (AR) and Forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), Breast Cancer Type 1 susceptibility protein (BRCA1), Poly [ADP-Ribose] Polymerase 1 (PARP1) and Na+/H+ Exchanger Regulatory Factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS) (p=0.045). A Kaplan-Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p=0.037), and the phenotypes TILs-/AR+ and TILs-/FOXA1- had a worse DFS (p=0.032, p=0.001 respectively). AR was associated with FOXA1 expression (p=0.007), and the tumors FOXA1+ presented low levels of TILs (p=0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p=0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments.

Lactobacilli are considered an inexhaustible source of potentially bioactive substances; indeed, several products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that cell-free supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, L. plantarum, L. rhamnosus and L. reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactobacilli on Candida virulence and to the production of metabolites which are able to impair fungal virulence. In the present work, stemming from those data, we deepened our knowledge on the CFS from these 4 lactobacilli by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactobacilli. Interestingly, L. rhamnosus showed the most peculiar metabolic profile. Specifically, after a hierarchical clustering analysis in positive and negative ionization mode, L. rhamnosus showed a specific area of significant overexpressed metabolites that strongly differed from the same area in other lactobacilli. In this area, inosine was identified among the overexpressed metabolites of L. rhamnosus. This molecule has been described to have antioxidant, anti-inflammatory, anti-infective and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity.

Trauma is one of the most common causes of death or permanent disability in young people, so a timely diagnostic approach is crucial. In polytrauma patients, CEUS has been shown to be more sensitive than US for the detection of solid organ injuries, improving the identification and grading of traumatic abdominal lesions with levels of sensitivity and specificity similar to those seen with MDCT. CEUS is recommended for the diagnostic evaluation of hemodynamically stable patients with isolated blunt moderate-energy abdominal traumas and for the diagnostic follow-up of conservatively managed abdominal traumas. In this pictorial review we illustrate the advantages and disadvantages of CEUS and the procedure details with tips and tricks during investigation of blunt moderate-energy abdominal trauma as well as during follow-up in non-operative management.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

Aim: to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET)-radiomics in lung cancer patients candidates or undergoing immunotherapy. Materials and Methods: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were in-dependently reviewed to evaluate study inclusion. Papers duplicate, out-of-topic, review or edi-torials articles and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the relies on radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. Results: 15 papers were included, 13 were qualified as conventional radiomics approaches, and two were as Deep Learning radiomics. The content of each study was different, indeed, 7 papers investigated the potential role of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreo-ver, 2 were relative to the prediction of response and 4 investigated the utility of radiomics to predict the response to immunotherapy. Finally, 2 papers were relative to the prediction of adverse events due to the immunotherapy. Conclusions: radiomics is promising in the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overpassed.

1) Background: We tested whether AHR activation induces DNA damage, whether polymorphisms in genes related to risk of Non-Hodgkin lymphoma are associated with DNA damage, and whether the two conditions do interact with each other. 2) Methods: Our study population included 36 subjects, randomly selected among the population controls participating in a case-control study on lymphoma in Sardinia, Italy, who donated a blood sample. We investigated 47 single nucleotide polymorphisms (SNPs) previously reported to convey risk of lymphoma; the Dual-Glo® Luciferase Assay System to detect activation of the aryl hydrocarbon receptor (AhR) by the serum of study subjects; and the COMET Assay to detect DNA damage. 3) Results: Activation of the aryl hydrocarbon receptor did not increase DNA damage in our study population. On the other hand, the mutant allele (G) of rs1056932/BCL6 increased the occurrence of DNA damage (p = 0.045); such association was confirmed among AhR negative, but not AhR positive subjects. 4) Conclusions: We observed excess DNA damage associated with a gene polymorphism, namely rs1056932/ BCL6, previously reported in association with risk of lymphoma. No increase in DNA damage was associated with AhR activation per se, nor with the other gene polymorphisms we investigated.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported even in specialized centers. Mobile health technologies have been used in research settings to overcome these limits with contrasting results. This study aims to evaluate the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Patients were randomly assigned to standard care or standard care plus mobile app (2:1). The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: Seventy-five subjects were prospectively enrolled. At six months of follow-up, the m-app group showed significantly lower dropout rates compared to standard care(p=0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86,95%C.I. 1.39-10.42,p=0.01). After one year of follow-up, we observed lower albeit non statistically significant dropout rates in the m-app compared to the standard care group(p=0.24). No differences were observed in terms of z-score BMI and percentage of BMI reduction between the two groups. Conclusion: our findings suggest that mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

Companion animals are increasingly being recognized as important contributors to the spreading of antimicrobial resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania region, Italy by analyzing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescription were collected considering the drug delivery (systemic or local) and the rationale for the treatment chosen. In the period under investigation, 166879 drugs were prescribed of which 129116 (73.37 %) were antimicrobial. A total of 83965 (65.03 %) antibiotics were prescribed to dogs, 40477 (31.35 %) to cats, and 4674 (3.62 %) to other companion animals. In dogs the 90.48 % of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely commonly prescribed class were fluoroquinolones. The main prescribed antimicrobials were the metronidazole-spiramycin (29.71%), amoxicillin-clavulanic (19.58%), enrofloxacin and cephalexin in dogs (16.52 %) and enrofloxacin (22.64%) and amoxicillin-clavulanic acid (21.37 %) in cats. Based on the results the wide use of broad-spectrum or second-line antibiotics is emerged together with the use of the critically important antimicrobials for human medicine.

Vaccination, particularly against pneumoccus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients, never practiced before, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics of the Geriatrics section, University Hospital of Palermo (Italy). A total of 101 vaccinations were carried out. Half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among participants, 46.3% received only vaccination against Pneumococcus and 26.8% only anti-influenza or the combination of anti-pneumococcus and anti-influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2 % of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejections, namely 74.8% for influenza and 29.5% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings is possible. Proposing influenza and pneumococcal vaccination for outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

The management of erectile dysfunction (ED) shows several grey zones, especially in terms of patient satisfaction and adherence to the treatment. The main and first-line treatment for ED is drug therapy, mainly phosphodiesterase-5 inhibitors (PDE-5is) but the adherence to the therapy is not optimal due to the low patient satisfaction reported in several cases. To address this issue, different administration routes and PDE-5is pharmacological formulations have been introduced in the pharmacological market. The pharmaceutical market has recently seen the introduction of a novel sildenafil oral suspension. This device offers access to all therapeutic regimens in one device, releasing 0.5 mL of suspension containing 12.5 mg of sildenafil with each pulse. This formulation enables tailored dosing based on clinical requirements and the demands of ED patients. Here, we aim to give a brief narrative review of the management of this new oral suspension in order to provide the readers with some suggestions to use in everyday clinical practice, on the basis of the recent evidence, by using an easy and rapid-to-consult questions and answers form. Also included are the conclusions of a board meeting of experienced andrologists regarding the most recent developments in this area.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

Background: In regenerative dentistry the graft material influences the success. It should act as an osteoconductive scaffold, providing a mineral substrate during resorption and inducing the activity of osteoinductive cells capable of producing new bone, platelet growth factors, and cell differentiation factors inducing the differentiation of undifferentiated mesenchymal cells into. Given that dentin shares many biochemical characteristics with bone tissue, it has recently attracted considerable interest as a biomaterial for bone repair. The aim of this study is to compare two grinder types in order to determine the optimal method for producing dentinal particles using a mechanical grinder. Materials and methods: A sample of 40 natural human teeth without restorations, prostheses or root canal treatments was used and divided into two groups subjected to two different grinder speeds (high-speed and low-speed). The high-speed showed a greater dispersion (53.5+-9.89% of the tooth) due to the pulverisation (highly thin granules) of part of the tooth. The low-speed grinder does not pulverize the dentin and the percentage of tooth loss is 9.16+/-2.34%. Conclusion: The low-speed gringer allows to save a major part of the tooth and to have a maximum quantity of graft material but requires more time. Further studies must be promoted to optimise the grinding procedures.

In the era of multi-omic sciences, dogma on singular cause-effect in physio-pathological processes is overcome and system biology approaches have been providing new perspectives to see through. In this context, extracellular vesicles (EVs) are offering a new level of complexity, given their role in cellular communication and their activity as mediators of specific signals to target cells or tissues. Indeed, their heterogeneity in terms of content, function, origin and potentiality contribute to the cross-interaction of almost every molecular process occurring in a complex system. Such features make EVs proper biological systems being, therefore, optimal targets of omic sciences. Currently, most studies focus on dissecting EVs content in order to either characterize it or to explore its role in various pathogenic processes at transcriptomic, proteomic, metabolomic, lipidomic and genomic levels. Despite valuable results are being provided by individual omic studies, the categorization of EVs biological data might represent a limit to be overcome. For this reason, a multi-omic integrative approach might contribute to explore EVs function, their tissue-specific origin and their potentiality. This review summarizes the state-of-the-art of EVs omic studies, addressing recent research on the integration of EVs multi-level biological data and challenging developments in EVs origin.

Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosa of the oral cavity, pharynx, and larynx. The methylation levels of Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in ccfDNA are considered pan-cancer biomarkers and have shown prognostic value in preliminary reports in HNSCC. Liquid biopsy is a non-invasive procedure that collects tumor-derived molecules including circulating cell-free DNA (ccfDNA). Here, we developed a ddPCR-based assay to detect the DNA methylation levels of plasma circulating SEPT9 and SHOX2 in patients with HNSCC. We first set up the assay on commercial methylated and un-methylated DNA. Then, the dynamic changes of the methylation levels of SEPT9 and SHOX2 were quantified in 20 patients during the follow-up. The results highlighted: i) the capability of the ddPCR-based assay in detecting very low copies of methylated molecules; ii) the significant decrease in methylation levels of SEPT9 and SHOX2 in plasma of HNSCC patients at the first time points of follow-up respect to T0; iii) a different trend of longitudinally DNA methylation variations associable to the clinicopathological features of the patients. The absolute quantification of the methylation levels of SEPT9 and SHOX2 in HNSCC may be used for risk stratification and disease monitoring.

Rhabdomyolysis is a serious clinical condition, which if left untreated can lead to kidney failure and in extreme cases, to death. It has also been reported in association with SARS COV2 infection and can be its initial presentation. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), which has many variants that change the characteristics of the disease affecting, among other things, the method of transmission or treatment. Some investigators have implicated excessive immune response in the causes of muscle damage during SARS-CoV-2 infection. Others point to direct damage caused by the virus or involving immune factors. In this study we described cases of COVID-19 infection from 1 June 2022 to 15 July 2022 with elevated muscle enzymes in the blood and hospitalized to the first division of Cotugno hospital in Campania. Of 39 patients with SARS-CoV-2 infection, 15 patients presented also rhabdomyolysis. The most common symptoms were: asthenia, fever, arthomyalgia, lipothymia and syncope. No patient had myocardial infarction and 2 patients had atrial fibrillation. All patients were affected by omicron SARS-CoV-2 variants. Of these patients: 4 patients died (2 due to rhabdomyolysis and 2 due to sepsis) and only one patient presented acute kidney injury.

Plant-Derived Extracellular Vesicles (PDEVs) contain high levels of antioxidants, especially when deriving from organic. PDEVs from different vegetal sources has shown an increased antioxidant power, compared to PDEVs from single plants, suggesting a synergistic effect of the bioactives constitutively expressed in the PDEVs from single fruits. With this study we wanted to investigate the beneficial effects of a mix of PDEVs on human skin cells. We found detectable levels of Citric Acid, Ascorbic Acid, Glutathione, Catalase and SOD in a mix of PDEVs deriving from 5 different fruits (Grape, Red Orange, Papaya, Pomegranate and Tangerine). We then treated H2O2-conditioned fibroblasts with the mix of PDEVs. The results showed that the PDEVs ‘mix reverted the H2O2-induced redox imbalance, restoring the mitochondrial homeostasis, with a strong reduction of mitochondrial anion superoxide and increase of sirtuin levels. The antioxidant action was consistent with a wound repair on a lesion produced in a Fibroblasts’ monolayer. This result was consistent with an increased level of Vimentin and Matrix Metalloproteinase-9, whose expression is directly related to the efficiency of the reparative processes. These data support a beneficial role of PDEVs in both preventing and treating skin injuries, through their potent antioxidant and reparative activities.

In this paper, we present demographic, clinical, anamnestic, cognitive, and functional data, as well as haematological, haematochemical, immunological and genetic parameters of an exceptional individual: Antonino Turturici, a semi-supercentenarian who held the title of the oldest living Italian centenarian from December 28, 2020, to September 23, 2021. The purpose of this study is to offer fresh insights into extreme phenotypes, with a particular focus on immune-inflammatory parameters. To the best of our knowledge, this study represents the first phenotypic investigation of a semi-supercentenarian, illustrating both indicators of age-related immune phenotype (ARIP) recognized as significant gauges of biological ageing and INFLA-score, a metric designed to assess the cumulative impact of inflammatory markers. The aim of this study was, indeed, to advance our understanding of the role of immune-inflammatory responses in achieving extreme longevity. The results bolster the idea that the immune system can play a role in promoting extreme longevity. However, this does not exclude the involvement of other body systems or organs in achieving extreme longevity.

No abstract available

An 8-months old male American Staffordshire terrier was referred for a no weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence caused by hematogenous osteomyelitis. Orthopedic, radiographic and tomographic examinations revealed a bone sequestrum of 4 x 1.4 cm and active periosteal reaction of the caudo-lateral cortical in the metaphysis and the distal third of the right femoral diaphysis, medullary osteolysis and interruption of the cranio-medial cortical profile, with involvement of the femoral trochlea leading to a secondary medial patella luxation. Once skeletally mature, after 4 months from surgical debridement and aggressive antibiotic therapy against Klebsiella oxytoca revealed by bacteriological exam, the patient underwent prosthetic surgery for the application of a custom-made patellar groove replacement (PGR) to fill the bone defect and restore the femoral trochlea surface. Despite the serious injury that afflicted the right pelvic limb, the surgery had satisfactory outcomes until the last 18-months postoperative follow up.

Aims: To date, precision medicine plays a pivotal role in the clinical administration of solid tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently investigated in clinical trials. A pitfall in the molecular tests is the diagnostic routine sample available to analyze predictive biomarkers; scant tissue sample often represents the only diagnostical source of nucleic acids to assess molecular analysis. At the sight of these critical issues, Next Generation Sequencing (NGS) platforms emerged as referral testing strategy for molecular analysis of predictive biomarkers in routine practice but high-skilled personnel, extensive working-time drastically impact on the widespread diffusion of this technology in diagnostic setting. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with NGS based diagnostic workflow by a referral institution. Methods: A retrospective series of n=64 samples (n=32 DNA, n=32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion) were retrieved from internal archive of University of Naples Federico II. Each sample was tested by adopting Oncomine Precision Assay (OPA), able to detect 2769 molecular actionable alterations [hot spot mutations, copy number variations (CNV) and gene fusions on fully integrated NGS platform (Genexus, Thermofisher Scientifics. (26,27) Concordance rate between these technical approaches was carried out. Results: Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between OPA and SiRe™ panel both for DNA and RNA based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) was assessed. Conclusions: Fully automatized Genexus system combined with OPA (Thermofisher Scientifics) may be considered a technically valuable, saving time sequencing platform to test predictive biomarkers in diagnostic routine practice.

Prevalence studies of current smoking among hospitalized COVID-19 patients demonstrated an unexpectedly low prevalence of current smoking among patients with COVID-19. The aim of the present proposal was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 hours from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades and the identification of differential glycemic responders can aid tailored treatment for prevention of pre-diabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among partic-ipants with elevated T2DM risk, to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary inter-vention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females, 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distin-guish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

In 2021, amidst the COVID-19 pandemic and global food insecurity, the Nigerian poultry sector was yet exposed to highly pathogenic avian influenza (HPAI) virus and its economic challenges. Between 2021 and 2022, HPAI caused 467 outbreaks reported in 31 of the 37 administrative regions in Nigeria. In this study, we characterized the genome of 97 influenza A viruses of the subtypes H5N1, H5N2 and H5N8 identified in different agro-ecological zones and farms during the 2021-2022 epidemic. The phylogenetic analysis of the HA genes showed widespread distribution of the H5Nx clade 2.3.4.4b and similarity with the HPAI H5Nx viruses detected in Europe since late 2020. Topology of the phylogenetic trees indicates the occurrence of several independent introductions of the virus into the country followed by a regional evolution of the virus most probably linked to its persistent circulation in West African territories. An additional evidence of the evolutionary potential of HPAI viruses circulating in this region is the identification in this study of a putative H5N1/H9N2 reassortant virus in a mixed-species commercial poultry farm. Our data confirm Nigeria as a crucial hotspot for HPAI virus introduction from the Eurasian territories and reveal a dynamic pattern of avian influenza virus evolution within the Nigerian poultry population.

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.

The medical use of Cannabis has a very long history. Although many principles are present in cannabis, called cannabinoids, Δ9tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and can-nabinol (CBN) are the three main cannabinoids most present and described. CBD itself is not re-sponsible for psychotropic effects of cannabis since does not produce the typical behavioral effects associated to the consumption of this drug. Cannabidiol (CBD) has recently gained growing at-tention in modern society and seems to be more and more explored in dentistry. Several subjective findings suggest some therapeutic effects of CBD, which are strongly supported by research evi-dence. However, there is a plethora of data regarding CBD’s mechanism of action and therapeutic potential, which are in many cases contradictory. We will first provide an overview of scientific evidence on the molecular mechanism of CBD’s action. Furthermore, we will map the recent de-velopments regarding possible oral benefits of CBD. In summary, we will highlight CBD’s prom-ising biological features for dentistry application, despite exiting patents suggest current the compositions for oral care as the main interest for industry.

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, anti-ageing effects to protect normal tissues and can exert anti-angiogenic, and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is enriched in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. Purpose: This work aims to measure hematochemical, anthropometric and metabolomic parameters in volunteers assuming an OMWW dietary supplement, OliphenoliaⓇ (OMWW-OL). Methods: The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, and metabolomic parameters were analyzed before the intervention, at 30 days and 30 days after stopping consumption. Results: 29 volunteers were enrolled and 23 completed the study. The participants’ parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, weight and body mass index instead of increasing slightly decreased, particularly in women. Also, hydration increased, especially in women, while blood pressure, glycemia and insulin decreased. Cholesterol, low-density and high-density lipoproteins and triglycerides were stable while vitamin D levels, alongside calcium, sensibly increased. Albumin also increased and parameters related to sarcopenia displayed promising, although not statistically significant, trends toward positive effects. All the values were in support of an equilibrium with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and vitamin D/unknown metabolite ratio. Conclusions: Supplementation of OMWW-OL has no detrimental effects and, although with limited potency of a pilot study, might imply the beneficial modulation of several biological parameters, being potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant as anti-ageing and in cancer prevention.

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.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

The rapid emergence and worldwide detection of the SARS-CoV-2 omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and more strong vaccine breakthrough ability. Also known as B.1.1.529, Omicron has four sub-variants, BA.1, BA.2, BA.3, and BA.4. Among them, BA.1 is the currently prevailing sub-variant, BA.2 is found to be able to alarmingly re-infect patients initially infected by omicron BA.1. BA.3 sub-variants is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today emerging is the BA.4, herein described and first detected in Italy, harboring a new mutation, specifically a deletion in the ORF 1 ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants pointed out that the deletion was not present previously and was never reported until now. Therefore, we can speculate that omicron BA.4; will become a new dominating “variant of concern” and might also break vaccine protection . On the other hand, we show that other proteins are mutated in the BA.4 in particular, seven mutations are recognized in the nucleocapsid (N) protein, the capability of five different types of rapid antigenic tests to recognize it.

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p&lt;0.001; p&lt;0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

Renal cell carcinoma (RCC) represents around 3% of all cancers, within which clear cell RCC (ccRCC) are the most common type (70–75%). The RCC disease regularly progresses asymptomatically and upon presentation is recurrently metastatic, so an early method of detection is necessary. The identification of one or more spe-cific biomarkers measurable in biofluids (i.e urine) by combined approaches could surely be appropriate for this kind of cancer, especially due to easy obtainability by non invasive method. OLR1 is a metabolic gene that encodes for the Lectin-like oxidized low-density lipoprotein re-ceptor-1 (LOX-1), implicated in inflammation, atherosclerosis, ROS and metabolic disor-der-associated carcinogenesis. Specifically, LOX-1 is clearly involved in tumor insurgence and progression of different human cancers. This work reports for the first time the presence of LOX-1 protein in ccRCC urine and its peculiar distribution in tumoral tissues. In parallel, urine samples headspace has been analyzed for the presence of the volatile compounds (VOCs) by SPME-GC/MS and gas sensor array. In particular, it was found by GC/MS analysis that 2-Cyclohexen-1-one,3-methyl-6-(1-methylethyl)- correlates with LOX-1 concentration in urine. Thus, the combined approach of VOCs analysis and protein quantification could led to promis-ing results in terms of diagnostic and prognostic potential for ccRCC tumor.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

Reducing levels of low-density-lipoprotein-cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk, and with LDL-C above 70 mg/dl. They were randomly divided in two groups: bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group including patients who doubled the dose of statin. At 12-weeks, BA group presented a greater significant decrease of LDL-C compared to ST group (-22.9% vs 7.5% p 0.002). Total-cholesterol decreased significantly in the BA group compared to ST (-14.8% vs-4.7% ; p 0.013) No significant between-groups changes in HDL and triglycerides occurred. At 12 weeks the number of patients who reached LDL-C lower than 70 mg/dl was 38 (63%) in the BA group versus 22 (37%) in the ST group (between group p 0.034). In the BA group the LDL lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of Bempedoic acid to statin/ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C. levels and increased the number of patients reaching the LDL-C goal.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

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.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.