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Transport Demand Management (TDM) is crucial in shaping travel behavior and enhancing urban mobility by promoting sustainable transport options. This study represents a comprehensive analysis of employee commuting behavior across seventy-seven cities in Italy, with a focus on Rome as a case study. It investigates some requirements of the workplace travel plan as a TDM strategy for promoting sustainable commuting. An online survey conducted in June 2022 yielded 2314 valid responses, including 1320 from private car drivers. K-means clustering was used to identify distinct behavioral patterns among commuters, revealing four clusters based on demographic factors and transport preferences, such as age, gender, family circumstances, vehicle ownership, willingness to walk, ride bicycles, or e-scooters, and reasons for mode choice. This study analyzed Rome’s public transport network, land use, and private car use. Results underscore the need for tailored transport policies that enhance inclusivity and accessibility, especially for employees with family members who cannot commute independently. A spatial analysis of Rome reveals significant infrastructure deficiencies, such as complicated transfers and inaccessible stations, which discourage PT use. Future research should explore the impact of remote work and psychological factors and conduct in-depth subgroup analyses to inform inclusive transport policy development.

The corallivorous snails Coralliophila meyendorffii and its coral host Parazoanthus axinellae are appealing candidates for studying symbiotic interactions at the microbiome level. In this study, we investigated for the first time the microbial community in the stomach of C. meyendorffii and in the polyps of its coral host P. axinellae using as markers multiple regions of the 16S rRNA gene. The bacterial community in the stomach of another corallivorous snail, Babelomurex cariniferus, that feeds on Cladocora hexacorals, was also investigated for comparison. The obtained results indicated the phylum Proteobacteria as the most abundant among the analysed samples, with Alphaproteobacteria and Gammaproteobacteria as the main classes. Among the investigated communities, some bacterial taxa were recognised in line with previous findings in the microbiota of marine invertebrates. As both organisms are exposed to the same bacteria in their habitats, this might suggest shared environmental influences for their microbiota composition. Most of the detected taxa found exclusively or predominantly in P. axinellae samples suggest the presence of holobiont components within the microbial community of this coral, mirroring those identified in other corals, while the stomach microbiome of C. meyendorffii did not indicate a primary role in parasitism. Finally, we provide evidence that many of these bacterial taxa are horizontally transferred between Parazohantus and Corallliophila.

The drive for the development of systems that can simultaneously investigate chemical and morphological information comes from the requisite to fully understand the structure and chemical reactivity relationships of materials. This is particularly relevant in photocatalysis, a field ruled by surface interactions. An in-depth understanding of these complex interactions could lead to significant improvements in materials design, and consequently, in photocatalytic performances. Here, we present a first approach to a combined atomic force microscopy (AFM) and Raman spectroscopy characterization of anodic TiO2 nanotubes arrays decorated with Ag nanoparticle electrodeposition from either the same anodizing organic electrolyte or from an aqueous one. Photocatalytic substrates were used in up to 15 consecutive photocatalysis tests to prove their possible deterioration with reuse. Sample aging can, in principle, produce changes in both the morphology and the chemical compounds that characterize the photocatalyst surface. Adopting multiple characterization techniques, such as a combination of AFM and Raman spectroscopy in an original setup, can profitably enable the observation of surface contamination. A significant drop in photocatalytic activity was observed after 10 cycles on samples where silver was deposited from the organic electrolyte, while the others remained stable. Such a drop was ascribed to photocatalyst deactivation. While in other cases, a simple recovery treatment allowed the initial photoactivity to be restored, this deactivation was not restored even after chemical and thermal cleaning treatments.

Mental imagery is a cognitive ability that enables individuals to simulate sensory experiences without external stimuli. This complex process involves generating, manipulating, and experiencing sensory perceptions. Despite longstanding interest, understanding its relationship with other cognitive functions and emotions remains limited. This narrative review aims to address this gap by exploring mental imagery’s associations with cognitive and emotional processes. It emphasizes the significant role of mental imagery on different cognitive functions, with a particular focus on learning processes in different contexts, such as school career, motor skill acquisition, and rehabilitation. Moreover, it delves into the intricate connection between mental imagery and emotions, highlighting its implications in psychopathology and therapeutic interventions. The review also proposes a comprehensive psychometric protocol to assess mental imagery’s cognitive and emotional dimensions, enabling a thorough evaluation of this complex construct. Through a holistic understanding of mental imagery, integrating cognitive and emotional aspects, researchers can advance comprehension and application in both research and clinical settings.

The present study is aimed at the characterization of artifacts excavated in the necropolis surrounding the mausoleum of the Aga Khan in Aswan (Egypt), as part of the Mummies Investigations Anthropological & Scientific West Aswan Necropolis (MIASWAN) project. Four cartonnages and some pottery shards were investigated on-site by means of non-destructive and micro-destructive techniques, such as attenuated total reflection/Fourier transform infrared spectroscopy (ATR/FTIR) and visible reflectance spectroscopy Vis-RS). Thanks to the use of these techniques, several pigments employed in the creation of the artifacts were identified. Due to the impossibility of transporting the investigated objects out of Egypt, a first-ever on-site characterization of the artifacts from this important excavation was carried out through scientific methodologies. These extreme conditions made the use of analytical instrumentation very challenging. Nevertheless, several characteristic pigments and hues were successfully identified.

Airport areas generate significant air pollution from both air and surface traffic. Policy makers often address this by considering single contributions, either from rubber-tired vehicles or aircraft, leading to an underestimation of the non-considered-mode’s impact. Similarly, literature on airport pollution often focuses on specific case studies, evaluating either surface or air traffic. Understanding the overlap of these contributions requires calculation of emissions from both traffic modes. This raises two research questions: which is the major contributor, and what mitigation measures can be applied? This paper addresses these questions through two Italian case studies. In the first, we estimated emissions from passenger cars, buses, and aircraft in a medium-sized airport representative of similar facilities across Italy and Europe, calculating emissions using COPERT for surface modes and ICAO methodologies for each LTO cycle. Results showed that aircraft emissions were significantly higher than those from surface vehicles. To address this, the second case study examined four mitigation measures at take-off and landing at another Italian airport, recalculating emissions via the same methodologies. The paper details the methodology process, presents results, and discusses the management of air-operations’ effects at urban airports within local mobility policies and practice, all within the research goal of advancing knowledge farther afield.

Properly managing aquatic organisms is crucial, including protecting endemic species and controlling invasive species. From a circular economy perspective, the sustainable use of aquatic species as a source of bioactive molecules is an area that is increasingly being explored. This includes the use of non-edible portions of seafood, which could pose considerable risks to the environment due to current methods of disposal. Therefore, it is of paramount importance to ensure that the exploitation of these resources does not result in the transfer of pollutants to the final product. This study analyzed two types of non-edible parts from the crayfish Procambarus clarkii: the abdominal portion of the exoskeleton (AbE) and the whole exoskeleton (WE), including the cephalothorax. These portions could potentially be utilized in the context of eradication activities regulated by local authorities. A screening analysis of four classes of pollutants, including pesticides, per- and polyfluoroalkyl substances (PFAS), phthalic acid esters (PAEs), and trace elements (TEs), was performed. The only analytes detected were TEs, and significant differences in the contamination profile were found between AbE and WE. Nevertheless, the levels recorded were comparable to or lower than those reported in the literature and below the maximum levels allowed in the current European legislation for food, suggesting that their potential use is legally permitted. In terms of scalability, the utilization of the entire non-edible P. clarkii portion would represent a sustainable solution for the reuse of waste products.

The Ionian Sea is a crucial intersection for various water masses in the Mediterranean. Its hydrography and dynamics play a significant role in the seawater budgets and biogeochemistry of the neighboring sub-basins. Multiple theories have been formulated to gain a better understanding of the Ionian dynamics. These theories primarily attribute the variability of the near-surface Ionian circulation to internal processes. Here, we utilize horizontal currents and temperature–salinity profiles from the Copernicus reanalysis to examine the contribution of baroclinic modes to the variability of the basin horizontal circulation. Our findings demonstrate that, although the basin vertical structure is characterized by three layers, the primary patterns of the Ionian circulation can be attributed to the first baroclinic mode. This mode, along with the barotropic mode, accounts for over 85% of the overall variability in the Ionian circulation, suggesting that only one of the three interfaces separating the different water masses in the basin is dynamically active. We estimate the depth of this interface to be about 490 m. Additionally, our analysis shows that more than 90% of the kinetic energy over the water column is localized above this interface, indicating that the deep layer of the Ionian is dynamically nearly inert.

Introduction: Oncological patients face numerous challenges throughout their cancer journey while navigating complex medical information. The advent of AI-based conversational models like ChatGPT (San Francisco, OpenAI) represents an innovation in oncological patient management. Methods: We conducted a comprehensive review of the literature on the use of ChatGPT in providing tailored information and support to patients with various types of cancer, including head and neck, liver, prostate, breast, lung, pancreas, colon, and cervical cancer. Results and Discussion: Our findings indicate that, in most instances, ChatGPT responses were accurate, dependable, and aligned with the expertise of oncology professionals, especially for certain subtypes of cancers like head and neck and prostate cancers. Furthermore, the system demonstrated a remarkable ability to comprehend patients’ emotional responses and offer proactive solutions and advice. Nevertheless, these models have also showed notable limitations and cannot serve as a substitute for the role of a physician under any circumstances. Conclusions: Conversational models like ChatGPT can significantly enhance the overall well-being and empowerment of oncological patients. Both patients and healthcare providers must become well-versed in the advantages and limitations of these emerging technologies.

Background: Oral and implant surgery represent highly specialized fields within dentistry that require a deep understanding of complex anatomical structures, together with practical hands-on experience. The present review examines common trends in oral and implant surgery training, focusing on how traditional methods like donated body dissection coexist with different and modern educational tools, and highlights the pros and cons of the different approaches in order to optimize training outcomes. Methods: A systematic literature search was carried out using the databases PubMed and Cochrane Library including the last 10 years of published articles about training in oral surgery and implantology. Starting from a total of 1319 studies, 47 were included to be carefully evaluated, and 20 studies were finally selected for this narrative review. The studies utilize methodologies such as randomized controlled trials (RCTs), cross-sectional surveys, case–control studies, and systematic reviews. The results were thematically organized, highlighting key quantitative outcomes and drawing connections between the different educational approaches. Results: From the narrative review, it emerged that oral and implant surgery training requires a careful balance between traditional methods, such as donated human body dissection, and modern technological advancements like virtual simulations and synthetic models. While animal and synthetic models have specific uses, their application remains limited in replicating the full complexity of human anatomy. These last technologies offer flexibility and expanded access to education but do not substitute for the hands-on experience gained through donated human body dissection. Conclusions: As educational institutions continue to evolve their training programs, ensuring access to human body dissection remains of paramount importance. Combining the strengths of both traditional and modern approaches may help optimize oral and implant surgery education, enhancing student preparedness without overlooking the critical value of direct anatomical experience.

Background/Objectives: Non-invasive ventilation (NIV) has emerged as a possible first-step treatment to avoid invasive intubation in pediatric intensive care units (PICUs) due to its advantages in reducing intubation-associated risks. However, the timely identification of NIV failure is crucial to prevent adverse outcomes. This study aims to identify predictors of first-attempt NIV failure in PICU patients by testing various machine learning techniques and comparing their predictive abilities. Methods: Data were sourced from the TIPNet registry, which comprised patients admitted to 23 Italian Paediatric Intensive Care Units (PICUs). We selected patients between January 2010 and January 2024 who received non-invasive ventilation (NIV) as their initial approach to respiratory support. The study aimed to develop a predictive model for NIV failure, selecting the best Machine Learning technique, including Generalized Linear Models, Random Forest, Extreme Gradient Boosting, and Neural Networks. Additionally, an ensemble approach was implemented. Model performances were measured using sensitivity, specificity, AUROC, and predictive values. Moreover, the model calibration was evaluated. Results: Out of 43,794 records, 1861 admissions met the inclusion criteria, with 678 complete cases and 97 NIV failures. The RF model demonstrated the highest AUROC and sensitivity equal to 0.83 (0.64, 0.94). Base excess, weight, age, systolic blood pressure, and fraction of inspired oxygen were identified as the most predictive features. A check for model calibration ensured the model’s reliability in predicting NIV failure probabilities. Conclusions: This study identified highly sensitive models for predicting NIV failure in PICU patients, with RF as a robust option.

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of fertile age. Some studies suggest that a ketogenic diet (KD) may have a role in treating PCOS. We aimed to demonstrate the long-term effectiveness of a KD in PCOS. Methods: Eighteen patients with PCOS phenotype A were enrolled: 28% were of normal weight, 28% were overweight, and 44% had obesity. All participants followed a KD without meal replacements for 45 days. After this period, patients underwent gradual carbohydrate reintroduction over 45 days, and thereafter healthy eating indications were given. Twelve patients completed the study. The patients were assessed at baseline and after 6 months. Anthropometric data, body composition, pelvic ultrasound, blood chemistry, hirsutism, and menstrual cycles frequency were recorded; Results: Besides improvement in anthropometric parameters, menstrual cycles (p 0.012), ovarian volume (p 0.029), FSH (p 0.05), LH (p 0.037), and progesterone (p 0.017) improved independently of weight or fat loss. However, testosterone and hirsutism improvements were influenced by weight and fat mass reduction. Conclusions: Our study showed that a KD followed by gradual carbohydrate reintroduction in PCOS has beneficial effects medium term, mostly independent of body weight loss, even in normal-weight women, suggesting that nutritional ketosis exerts beneficial effects per se.

Multidrug-resistant Klebsiella pneumoniae is a significant healthcare challenge that particularly affects vulnerable patients through opportunistic nosocomial infections. Surveillance is crucial for monitoring the prevalence of these infections. Eighty-four KPC K. pneumoniae strains (2019–2022) were collected from patients admitted in Fondazione Policlinico Universitario Campus Bio-Medico. Strains were identified by MALDI-TOF and tested for antimicrobial susceptibility, and gene amplification was performed to identify the different blaKPC variants. Phylogenetic reconstructions were carried out using Bayesian methods. Additionally, to create a Bayesian skyline plot (BSP), additional analyses were conducted, running a simulation of 100 million generations under a Bayesian skyline model along with the uncorrelated log-normal relaxed clock model. To identify potential subgroups within genetic clusters and evaluate genetic variability among sequences, principal coordinate analysis (PCoA) was performed. In total, 84 Klebsiella pneumoniae isolates were classified as multidrug-resistant (MDR), characterized by resistance to three or more antibiotic classes, including carbapenems, and testing positive for KPC gene presence, and were included in the study. The Bayesian evolutionary tree for K. pneumoniae showed strongly supported branches but no genetic structure related to sampling dates or hospital departments. Phylogenetic analysis revealing a 73-year evolutionary span of K. pneumoniae strains. PCoA analysis identified three genetic outliers from 2022 and one from 2021, indicating higher genetic distances. The Bayesian skyline plot revealed increased genetic variability peaking at the end of 2019, followed by stabilization from early 2020 onward, with no significant changes in genetic variability thereafter. Overall, the study found no genetic structure correlating with sampling date or hospital department, suggesting significant variability in pathogen introduction during the pandemic. The increase in multidrug-resistant K. pneumoniae was linked to the influx of severe COVID-19 cases, prolonged hospitalizations, and heightened broad-spectrum antibiotic use, which likely facilitated resistance development and transmission amidst altered infection control practices.

Turbomachinery engines face significant failure risks due to the combination of thermal loads and high-amplitude vibrations in turbine and compressor blades. Accurate stress distribution measurements are critical for enhancing the performance and safety of these systems. Blade tip timing (BTT) has emerged as an advanced alternative to traditional measurement methods, capturing blade dynamics by detecting deviations in blade tip arrival times through sensors mounted on the stator casing. This research focuses on developing an analytical model to quantify the uncertainty budget involved in designing a calibration setup for BTT systems, ensuring targeted performance levels. Unlike existing approaches, the proposed model integrates both operational variability and sensor performance characteristics, providing a comprehensive framework for uncertainty quantification. The model incorporates various operating and measurement scenarios to create an accurate and reliable calibration tool for BTT systems. In the broader context, this advancement supports the use of BTT for qualification processes, ultimately extending the lifespan of turbomachinery through condition-based maintenance. This approach enhances performance validation and monitoring in power plants and aircraft engines, contributing to safer and more efficient operations.

Doping prevention transcends elite sports, highlighting a broader societal challenge where performance enhancement is driven by pressures to increase strength, beauty, and status. This issue extends to adolescents and non-competitive sports participants, where self-optimization pressures are increasingly normalized. Research underscores the need for tailored educational interventions that go beyond punitive measures, fostering ethical decision-making and personal responsibility. The recent literature emphasizes that addressing psychological protective factors, such as self-efficacy and emotional regulation, can effectively mitigate substance use risks. The project “Sport Informa” involved the educational community and adolescents between the ages of 16 and 19, with the goal of providing knowledge about the phenomenon of doping and acquiring tools useful for enhancing self-esteem and self-management skills, in order to prevent the risk of doping by promoting a balanced psychophysical development in young people. A 16 h online training program was delivered to high school teachers. The training provided knowledge about doping, its psychological and social implications, and practical tools for promoting protective factors in students. A longitudinal design was employed, with data collected before and after the intervention using validated psychometric tools, including the Self-Efficacy Scale, the Self-Compassion Scale, and the Emotional Regulation Questionnaire. Results showed significant improvements in teachers’ psychological dimensions, particularly in self-efficacy and emotional regulation, which they subsequently applied in their interactions with students. Finally, a survey was conducted with young participants who took part in the project activities to assess their self-evaluation of key factors relevant to designing future educational interventions and events aimed at preventing doping use.

This study investigates the critical relationship between soil characteristics, trace element concentrations in Nebbiolo grapes, and the resulting wine quality, emphasizing the importance of terroir in winemaking. Italy, particularly the regions of Piedmont, Lombardy, and the Aosta Valley, is home to Nebbiolo, a prestigious grape variety known for its depth and aging potential in wines like Barolo and Barbaresco. The research focuses on seventeen grape and wine samples, highlighting how soil mineral composition could affect grape composition and wine characteristics. The analysis employed ICP-AES (inductively coupled plasma atomic emission spectrometry) to measure trace elements such as Al, Ba, and Mn, linking their concentrations to the soil’s geological properties. Elements were categorized into three groups based on their origins—natural soil contributions (Al, Ba, Li, Mn, Mo, Sr, Ti), those influenced by production cycles (Ca, Mg, K, Cu, Zn, Fe), and artificial sources (Co, Cr, Ni, V)—asserting that the first group serves as the most reliable indicators for tracing wines back to their vineyard origins. By establishing a chemical fingerprint for Nebbiolo wines, this research aims to enhance their authenticity and market value while providing insights into the intricate interplay between soil, grape varietals, and winemaking practices and contemporary challenges like climate change and evolving market demands.

Background: To investigate functional and anatomical outcomes after pars plana vitrectomy (PPV) for lamellar macular hole (LMH) with a long-term follow-up. Methods: An interventional study on 14 patients (16 eyes) with LMH was conducted. The inclusion criteria included a minimum 36-month follow-up after PPV. The preoperative and postoperative best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography parameters were examined. Results: Preoperatively, the mean BCVA was 0.46 ± 0.22 LogMAR. Epiretinal proliferation (ERP) was visible in 81.25% of eyes. Outer retinal disruption was present in 31.25% of LMH cases. The average central foveal thickness (CFT) measured 183.68 ± 61.73 microns. The mean BCVA improved at each follow-up time point: it was 0.24 ± 0.16 LogMAR at 1 month, 0.18 ± 0.15 LogMAR at 6 months, and 0.09 ± 0.11 LogMAR at the last follow-up. There was a statistically significant improvement between BCVA at 1 month and BCVA at 6 months and between BCVA at 6 months and BCVA at the last follow-up (p < 0.001). BCVA improved in all eyes, with 87.5% achieving at least 0.3 LogMAR improvement. The mean CFT at the 1-month follow-up was 211.45 ± 43.55 microns, increased to 248.81 ± 48.51 microns at 6 months, and further increased to 278.37 ± 45.50 microns at the last follow-up. Foveal contour restoration was achieved in all eyes, and those with preoperative ellipsoid zone alterations demonstrated a complete repair of the external retinal layers. No intra or postoperative complications were recorded. Conclusions: In our series, PPV had a high success rate and was associated with a substantial functional improvement in LMH treatment, and this result was maintained and kept increasing until the last follow-up. Long-term follow-up is crucial for a comprehensive evaluation of the healing process and to assess the benefits of the surgical intervention.

The metabolic interplay between macrophages and cancer cells mirrors the plasticity of both kinds of cells, which adapt to the microenvironment by sustaining cell growth and proliferation. In this way, cancer cells induce macrophage polarization, and, on the other hand, tumor-associated macrophages (TAMs) contribute to the survival of cancer cells. In a simplified manner, macrophages can assume two opposite subtypes: M1, pro-inflammatory and anti-tumor phenotype, and M2, anti-inflammatory and protumor phenotype. How do cancer cells induce macrophage polarization? Any actor involved in tumor growth, including the mitochondria, releases molecules into the tumor microenvironment (TME) that trigger a subtype transition. These metabolic changes are the primary cause of this polarization. Hepatocellular carcinoma (HCC), the prevalent type of liver primary tumor, is characterized by cells with extensive metabolic adaptions due to high flexibility in different environmental conditions. This review focuses on the main metabolic features of M1 and M2 macrophages and HCC cells underlying their metabolic behavior in response to TME.

To the best of our knowledge, no studies in the literature have reported on the relationship between the pregnancy-associated glycoprotein (PAG) concentration and undernutrition during pregnancy in sheep. Therefore, the aim of this study was to investigate the effects of undernutrition on the blood concentration of PAGs in pregnant ewes carrying single and multiple fetuses, undergoing either dietary energy restriction or receiving 100% of their energy requirements during the period of maximal placenta growth. From d 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates, fulfilling either 100% of the ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 16 multiple pregnancies) or only 50% (feed-restricted group; n = 29; 11 singleton pregnancies, 18 multiple pregnancies). Blood samples were collected from all the ewes the day before intravaginal sponge insertion (T0) and, thereafter, every 30 days starting from d 24 of gestation (T1) until d 30 after parturition (T6), to determine the PAG, progesterone, NEFA, total protein, and glucose concentrations. Our results showed that PAG concentrations are not only influenced by the number of fetuses, but also by the ewe’s diet. In particular, the PAG marginal means were higher in the feed-restricted group than in the control group (7.8 ± 0.6 and 10.8 ± 0.9 ng/mL for the control and feed-restricted groups, respectively; p = 0.040). This finding confirms that a dietary restriction between d 24 and d 100 of gestation leads to a growth in placental functions as inferred from the increase in the concentration of the PAG levels. Therefore, the measurement of PAG concentrations, in addition to serving as a marker of pregnancy, can also serve as a marker of placental functionality.

Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, such as cell growth, inflammation, differentiation, immune-mediated responses and oncogenic transformation. The aim of this review is to review the literature concerning the role of several PTPs—PTPN22, PTPN2, PTPN6, PTPN11, PTPσ, DUSP2, DUSP6 and PTPRK—at the level of the intestinal mucosa in inflammatory bowel disease (IBD), celiac disease (CeD) and type 1 diabetes (T1D) in both in vitro and in vivo models. The results revealed shared features, at the level of the intestinal mucosa, between these diseases characterized by alterations of different biological processes, such as proliferation, autoimmunity, cell death, autophagy and inflammation. PTPs are now actively studied to develop new drugs. Also considering the availability of organoids as models to test new drugs in personalized ways, it is very likely that soon these proteins will be the targets of useful drugs.

Biostimulants include a wide array of microorganisms and substances that can exert beneficial effects on plant development and growth, often enhancing nutrient uptake and improving tolerance against abiotic and biotic stress. Depending on their composition and time of application, these products can influence plant physiology directly as growth regulators or indirectly through environmental condition changes in the rhizosphere, such as nutrient and water availability. This review evaluated 48 case studies from 39 papers to summarize the effects of biostimulant application on fruit and tuber yields and on the quality of processing tomato and potato in open field conditions. For potato, PGPR bacteria were the main studied biostimulant, whereas the low number of studies on processing tomato did not permit us to delineate a trend. The yield and quality were greatly influenced by cultivars and biostimulant composition, application method, period, and dose. For processing tomato, a positive effect of the biostimulant application on the marketable yield was reported in 79% of the case studies, whereas for potato, the effect was reported in only 47%. Few studies, on processing tomato and potato, also reported data for quality parameters with contrasting results. The variability of crop response to biostimulant application in open field conditions highlights the need for more comprehensive studies. Such studies should focus on diverse cultivars, deeply understand the interaction of biostimulant application with agronomic management (e.g., irrigation and fertilization), and evaluate yield and quality parameters. This approach is crucial to fully understand the potential and limitations of biostimulant applications in agriculture, particularly regarding their role in sustainable crop production.

The island of Malta, despite its small size, boasts a great variety of landscapes and landforms, offering a wide range of geological and geomorphological features of great interest. The identification and assessment of geosites can contribute to the preservation, protection, and promotion of this rich geodiversity. In addition, geosites have a high potential of attracting geotourists, thus also contributing to the development of the local economy. Tourism plays a key role for the Maltese Islands, with Malta’s tourism direct contribution to GDP being among the highest in Europe. Thus, geotourism could represent a significant resource for Malta, though it has yet to receive the attention and recognition it deserves. Within this framework, this work aims to highlight the role of geoheritage and geotourism as potential resources for the enhancement of sustainable tourism and geoconservation in the southern sector of Malta. This region of Malta receives less visitors compared with the northern sector of the island, which is popular for its sandy beaches. To this end, potential geosites were inventoried and quantitatively assessed using a commonly applied methodology tailored to the local setting. The results of this evaluation let to identify 18 potential geosites that can be recognized as both parts of the Maltese natural heritage and tourist resources. Among these 18 sites, we identified four priority geosites which could be incorporated into a potential geotourism route to also highlight the valuable elements of the cultural heritage located in the vicinity. Moreover, the assessment methodology, applied for the first time in the investigated area, has proven to be a valuable support for geosite identification and can be extended to other Maltese regions.

The early childhood period, encompassing prenatal and early stages, assumes a pivotal role in shaping cardiovascular risk factors. We conducted a narrative review, presenting a non-systematic summation and analysis of the available literature, focusing on cardiovascular risk from prenatal development to the first 1000 days of life. Elements such as maternal health, genetic predisposition, inadequate fetal nutrition, and rapid postnatal growth contribute to this risk. Specifically, maternal obesity and antibiotic use during pregnancy can influence transgenerational risk factors. Conditions at birth, such as fetal growth restriction and low birth weight, set the stage for potential cardiovascular challenges. To consider cardiovascular risk in early childhood as a dynamic process is useful when adopting a personalized prevention for future healthcare and providing recommendations for management throughout their journey from infancy to early adulthood. A comprehensive approach is paramount in addressing early childhood cardiovascular risks. By targeting critical periods and implementing preventive strategies, healthcare professionals and policymakers can pave the way for improved cardiovascular outcomes. Investing in children’s health during their early years holds the key to alleviating the burden of cardiovascular diseases for future generations.

Down syndrome (DS) is one of the most common chromosomal disorders. In addition to this variety of dysmorphic features. DS is also associated with a wide range of diseases and related comorbidities affecting different organs and systems. These comorbidities, together with societal and environmental influences, have a negative impact on physical activity in people with DS. Low levels of physical activity and energy expenditure have been identified as crucial players in worsening the acquisition of motor skills and executive functions. Executive functions are critical for the many skills (creativity, flexibility, self-control, and discipline) impacting our quality of life and make it possible to control impulses, mentally play with ideas, and stay focused. We proposed a broad overview of the available literature regarding motor skills and executive functions in pediatric patients with DS to understand the specific challenges for tailoring physical activity interventions. Motor skill interventions are effective in improving motor competence and performance on cognitive, emotional, and physical aspects in children with DS. Interventions based on executive functions in DS subjects are effective to contrast the cognitive decline and improve the everyday use of executive functions in youth and adults. Targeted interventions are mandatory for maximizing the benefits of physical activity, minimizing potential risks, and ultimately improving the overall health outcomes and quality of life for individuals with DS.

The major histocompatibility complex (MHC) consists of genes involved in immune response and molecular discrimination between self and non-self. MHC genes are the most polymorphic in vertebrates. The origin and maintenance of polymorphism in MHC genes in populations is still unresolved. Mechanisms such as sexual selection and heterozygote advantage have been suggested as explanations for this high variability. In this study, a farmed population of rainbow trout (Oncorhynchus mykiss) characterized by the presence of specific MHC class IIB gene haplotypes at a frequency higher (30%) than that expected from random matings was investigated. Therefore, it was hypothesized that disassortative matings occur with an adaptive advantage for females, resulting in improved reproductive performance when mated with individuals with similar MHC haplotypes. Genetic analyses of the breeders were performed to define the MHC haplotypes and to perform specific matings. The effect of mating was evaluated by analyzing the survival rate of the offspring at various stages of incubation until swim-up. The reproductive performance of the offspring derived from specimens with similar haplotypes showed a better survival trend during the first life stages and reduced malformations. The results obtained are in contrast with the heterozygous advantage theory, therefore it was hypothesized, as for other salmonid species, the presence of a positive selection towards locally adapted MHC genes that promotes reproduction between genetically similar individuals.

The recovery of potato waste for circular-economy purposes is a growing area of industrial research. This waste, rich in nutrients and potential for reuse, can be a valuable source of starch for packaging applications. Rheology plays a crucial role in characterizing film-forming solutions before casting. In this work, packaging film was prepared from potato waste using rheological information to formulate the film-forming solution. To this aim, rheological measurements were carried out on starch/glycerol-only samples, and the data obtained were used to optimize the formulation from the waste. The polyphenol content of the peels was analyzed, and the resulting films were comprehensively characterized. This included assessments of color, extensibility, Fourier-transform infrared (FT-IR) spectroscopy, surface microscopy, and contact angle. Polyphenol-loaded films, suitable for packaging applications, were developed from potato waste. These films exhibited distinct properties compared to those made with pure starch, including an improved wettability of about 75° for the best sample and a high elastic modulus of about 36 MPa, which reduces the deformability but enhances the resistance against the stress. Through rheological studies, we were able to design films from potato peel waste. These films demonstrated promising mechanical performance.

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that occurs predominantly in premature infants and is characterized by the inflammation and necrosis of the intestine, showing high morbidity and mortality rates. Despite decades of research efforts, a specific treatment is currently lacking, and preventive strategies are the mainstays of care. This review aims to help understand the complex interplay between gut microbiota and their metabolites in NEC pathogenesis. In particular, we focused on how these factors can influence gut health, immune responses, and intestinal barrier integrity. Discussion: Current research has increasingly focused on the role of the gut microbiota and their metabolites in NEC pathogenesis, thanks to their involvement in modulating gut health, immune responses, and intestinal barrier integrity. Conclusions: A deeper understanding of the interplay between gut microbiota and their metabolites is essential for developing personalized strategies to prevent NEC. By targeting these microbial interactions, new therapeutic approaches may emerge that offer improved outcomes for preterm infants at a high risk of NEC.

Background/Objectives: Osteoarthritis (OA) is the most common joint disease in the adult population. OA is the result of multiple mechanisms leading to inflammation and the degradation of the cartilage. A complex series of etiological actors have been identified so far, including extracellular vesicles (EVs). The EV content of the synovial fluid (SF) can release inflammatory mediators that enhance OA progression. An intra-articular viscosupplementation of high-MW hyaluronic acid (HyA) constitutes the first-line conservative treatment for OA. Although attractive for the potential pharmacological implications, the possibility that HyA may interact with EVs in the context of OA has not yet been specifically investigated; therefore, the present study aimed to fill this gap. Methods: We studied the effect of a HyA preparation (a blend of crosslinked and linear polymers, CLHyA) on the relevant inflammatory markers in chondrocytes (HC cells or primary chondrocytes isolated from patients with advanced OA) exposed to the EVs collected from IL-1β-stimulated THP-1 human monocytes (EVs+). Results: EVs+ caused specific inflammatory responses in chondrocytes that could be prevented by coincubation with CLHyA. This anti-inflammatory activity is likely dependent on the direct binding of CLHyA to CD44 receptors highly expressed in EVs+ and on the subsequent hindrance to EVs+ diffusion and docking to target cells. Conclusions: On the whole, the tight interactions identified herein between HMW HyA and EVs+ represent a novel, pharmacologically exploitable mechanism potentially relevant in the context of OA treatment.

Gunshot wound morphology and gunshot residues (GSRs) evaluation have been poorly investigated in veterinary forensic pathology. The aims of the present study were to assess the gunshot wound morphology in animals and evaluate the detectability of lead deriving from GSRs using colorimetric techniques. To these aims, cadavers were divided into four different groups. Group A comprised eight animals who died from firearm-related injuries, while groups B and C included dog limbs shot using different shooting ranges; group D comprised dog limbs stabbed with a screwdriver. Morphological analysis was performed on all entry gunshot wounds. Lead residues were investigated using a Bullet Hole Testing Kit (BTK) and Rhodizonate Sodium histochemical staining (NaR-s). Gunshot wounds in group A showed an abrasion ring associated with hemorrhages and tissue necrosis. Groups B and C showed injuries related to the shooting range. NaR-s showed positive results in both animals that died from gunshot wounds and experimentally shot limbs. However, the number of positive cases and the pattern of lead distribution varied with the shooting range. Positive results by BTK were limited to close-contact shots in group B limbs. Our results suggest that both pathological examination and NaR tests represent valid tools for investigating gunshot wounds in veterinary pathology.

Microglia-mediated neuroinflammation has been linked to neurodegenerative disorders. Inflammation and aging contribute to microglial senescence. Microglial senescence promotes the development of neurodegenerative disorders, including Alzheimer’s disease (AD). In this study, we investigated the anti-neuroinflammatory and anti-senescence activity of Honokiol (HNK), a polyphenolic neolignane from Magnolia officinalis Rehder & E.H Wilson, in comparison with its synthetic analogue Honokiol Hexafluoro (CH). HNK reduced the pro-inflammatory cell morphology of LPS-stimulated BV2 microglia cells and increased the expression of the anti-inflammatory cytokine IL-10 with an efficacy comparable to CH. HNK and CH were also able to attenuate the alterations in cell morphology associated with cellular senescence in BV2 cells intermittently stimulated with LPS and significantly reduce the activity and expression of the senescence marker ß-galactosidase and the expression of p21 and pERK1/2. The treatments reduced the expression of senescence-associated secretory phenotype (SASP) factors IL-1ß and NF-kB, decreased ROS production, and abolished H2AX over phosphorylation (γ-H2AX) and acetylated H3 overexpression. Senescent microglia cells showed an increased expression of the Notch ligand Jagged1 that was reduced by HNK and CH with a comparable efficacy to the Notch inhibitor DAPT. Overall, our data illustrate a protective activity of HNK and CH on neuroinflammation and cellular senescence in microglia cells involving a Notch-signaling-mediated mechanism and suggesting a potential therapeutic contribution in aging-related neurodegenerative diseases.

Time-lapse ground-penetrating radar (GPR) surveys, combined with automated infiltration experiments, provide a non-invasive approach for investigating the distribution of infiltrated water within the soil medium and creating three-dimensional images of the wetting bulb. This study developed and validated an experimental protocol aimed at quantifying and visualizing water distribution fluxes in layered soils under both unsaturated and saturated conditions. The 3D images of the wetting bulb significantly enhanced the interpretation of infiltration data, enabling a detailed analysis of water movement through the layered system. We used the infiltrometer data and the Beerkan Estimation of Soil Transfer parameters (BEST) method to determine soil capacitive indicators and evaluate the physical quality of the upper soil layer. The field survey involved conducting time-lapse GPR surveys alongside infiltration experiments between GPR repetitions. These experiments included both tension and ponding tests, designed to sequentially activate the soil matrix and the full pore network. The results showed that the soil under study exhibited significant soil aeration and macroporosity (represented by AC and pMAC), while indicators related to microporosity (such as PAWC and RFC) were notably low. The RFC value of 0.55 m3 m−3 indicated the soil’s limited capacity to retain water relative to its total pore volume. The PAWC value of 0.10 m3 m−3 indicated a scarcity of micropores ranging from 0.2 to 30 μm in diameter, which typically hold water accessible to plant roots within the total porosity. The saturated soil hydraulic conductivity, Ks, values ranged from 192.2 to 1031.0 mm h−1, with a mean of 424.4 mm h−1, which was 7.9 times higher than the corresponding unsaturated hydraulic conductivity measured at a pressure head of h = −30 mm (K−30). The results indicated that the upper soil layer supports root proliferation and effectively drains excess water to the underlying limestone layer. However, this layer has limited capacity to store and supply water to plant roots and acts as a restrictive barrier, promoting non-uniform downward water movement, as revealed by the 3D GPR images. The observed difference in hydraulic conductivity between the two layers suggests that surface ponding and overland flow are generated through a saturation excess mechanism. Water percolating through the soil can accumulate above the limestone layer, creating a shallow perched water table. During extreme rainfall events, this water table may rise, leading to the complete saturation of the soil profile.

Lower limb exoskeletons represent a relevant tool for rehabilitating gait in patients with lower limb movement disorders. Partial assistance exoskeletons adaptively provide the joint torque needed, on top of that produced by the patient, for a correct and stable gait, helping the patient to recover an autonomous gait. Thus, the device needs to identify the different phases of the gait cycle to produce precisely timed commands that drive its joint motors appropriately. In this study, EMG signals have been used for gait phase detection considering that EMG activations lead limb kinematics by at least 120 ms. We propose a deep learning model based on bidirectional LSTM to identify stance and swing gait phases from EMG data. We built a dataset of EMG signals recorded at 1500 Hz from four muscles from the dominant leg in a population of 26 healthy subjects walking overground (WO) and walking on a treadmill (WT) using a lower limb exoskeleton. The data were labeled with the corresponding stance or swing gait phase based on limb kinematics provided by inertial motion sensors. The model was studied in three different scenarios, and we explored its generalization abilities and evaluated its applicability to the online processing of EMG data. The training was always conducted on 500-sample sequences from WO recordings of 23 subjects. Testing always involved WO and WT sequences from the remaining three subjects. First, the model was trained and tested on 500 Hz EMG data, obtaining an overall accuracy on the WO and WT test datasets of 92.43% and 91.16%, respectively. The simulation of online operation required 127 ms to preprocess and classify one sequence. Second, the trained model was evaluated against a test set built on 1500 Hz EMG data. The accuracies were lower, yet the processing times were 11 ms faster. Third, we partially retrained the model on a subset of the 1500 Hz training dataset, achieving 87.17% and 89.64% accuracy on the 1500 Hz WO and WT test sets, respectively. Overall, the proposed deep learning model appears to be a valuable candidate for entering the control pipeline of a lower limb rehabilitation exoskeleton in terms of both the achieved accuracy and processing times.

Macrophages represent primary players of the innate immune system. Macrophage activation triggers several signaling pathways and is tightly associated with metabolic changes, which drive different immune subsets. Recent studies unveil the role of various metabolic enzymes in macrophage activation. Here, we show that malic enzyme 1 (ME1) is overexpressed in LPS-induced macrophages. Through chromatin immunoprecipitation, we demonstrate that ME1 transcriptional regulation is under control of NF-κB. Furthermore, ME1 activity is also increased in activated human PBMC-derived macrophages. Notably, ME1 gene silencing decreases nitric oxide as well as reactive oxygen species and prostaglandin E2 inflammatory mediators. Therefore, modulating ME1 provides a potential approach for immunometabolic regulation and in turn macrophage function.

Fungi belonging to the genus Trichoderma have received high consideration in agriculture due to their beneficial effects on crops from their plant promotion effects and protection from disease. A role of Trichoderma fungi in triggering plant defense mechanisms against insect pests, either directly or by natural enemy attraction, has been proposed, even if the results in different studies are controversial. In this present study, using zucchini plants as a model species, we investigated the effects of Trichoderma afroharzianum strain T22 plant inoculation on the cotton aphid Aphis gossypii and its endoparasitoid Aphidius colemani. Our results showed that the inoculation with T. afroharzianum T22 promotes A. gossypii population growth and makes zucchini more attractive to the aphid. The higher abundance of aphids on Trichoderma-inoculated zucchini was compensated for by a higher presence of the mummies of Aphidius colemani. In this present study, we recorded a higher zucchini biomass, thereby confirming that Trichoderma can act as a plant growth inducer.

Skeletal muscle secretome, through its paracrine and endocrine functions, contributes to the maintenance and regulation of overall physiological health. We conducted a narrative review on the role of skeletal muscle and exercise in maintaining glucose homeostasis, driving insulin resistance (IR), and preventing type 2 diabetes in pediatric populations, especially in the context of overweight and obesity. Myokines such as interleukin (IL)-6, IL-8, and IL-15, as well as irisin, myonectin, and myostatin, appear to play a crucial role in IR. Skeletal muscle can also become a target of obesity-induced and IR-induced inflammation. In the correlation between muscle, IR, and inflammation, the role of infiltration of the immune cells and the microvasculature may also be considered. It remains unclear which exercise approach is the best; however, combining aerobic exercise with resistance training seems to be the most effective strategy for managing IR, with high-intensity activities offering superior metabolic benefits and long-term adherence. Encouraging daily participation in enjoyable and engaging exercise is key for long-term commitment and effective glucose metabolism management. Promoting physical activity in children and adolescents must be a top priority for public health, not only in terms of individual quality of life and well-being but also for community health.

Background and Objectives: Binocular optical microscopy (OM) paved the way for a new era in brain and spine neurosurgery fields with the introduction of microsurgery. Despite its enormous contribution to modern neurosurgery, OM presents some intrinsic limitations that surgeons need to face during procedures such as prolonged non-ergonomic positions and decreased vision quality to the assistant eyepiece. To overcome these limitations, in recent years, new operative tools have been introduced, such as exoscopes. Here, we present our experience with exoscopes in spine surgery. Materials and Methods: In the period between January 2022 and December 2023, we gradually implemented the use of a high-definition 4K-3D exoscope (ORBEYETM, Olympus, Japan) in patients undergoing spinal surgery. Results: A total of 243 patients underwent spine surgery with exoscope magnification (47 intradural tumors, 99 lumbar degenerative cases, 79 cervical degenerative cases, 5 dorsal calcified disk herniations, 4 dural arteriovenous fistulas (dAVFs), and 9 others). We compared this cohort with a similar cohort of patients operated in the same period using OM based on different endpoints: operating time, complication rate, and infection rate. We did not find any statistically significant difference in any of the endpoints between these two groups. Conclusions: In our experience, the exoscope provides a better resolution of spinal anatomy and higher quality real-time images of the surgery for the entire OR team and improves the ergonomic posture of both surgeons, without lengthening the operating time and without increasing the rate of adverse events. Prospective studies with a larger cohort of patients are needed to further validate these findings.

Pesticides play a critical role in modern agriculture by protecting crops and ensuring higher yields, but their widespread use raises concerns about human health and environmental impact. Regulatory agencies impose Maximum Residue Levels (MRLs) to ensure safety, and the European Food Safety Authority (EFSA) assesses pesticide risks. This study monitored pesticide residues in 169 feed samples from Piedmont (Italy) collected between 2019 and 2023. Using GC-MS/MS, residues were found in 92% of animal-based and 70% of cereal-based feedstuffs. The most common pesticides in cereal-based feeds were pyrimiphos-methyl, deltamethrin, cypermethrin, azoxystrobin, and tetramethrin, and the pesticide synergist piperonyl-butoxide demonstrated a significant increase in contaminated samples in 2023. The lower concentrations in 2021 were likely due to COVID-19 impacts on pesticide availability. In animal-based feeds, common pesticides included deltamethrin, cypermethrin, and the pesticide synergist piperonyl-butoxide. The results highlight the pervasive presence of low-dose pesticide mixtures in feed and food chains, which could impact health, although do not pose acute risks. The study emphasizes the need for ongoing pesticide monitoring and awareness of the long-term effects of chronic pesticide exposure on animal, human, and environmental health.

Background. Oxidative stress and inflammation are typically implied in atherosclerosis pathogenesis and progression, especially in coronary artery disease (CAD). Our objective was to investigate the oxidative stress and inflammation burden directly associated with atherosclerotic plaque in patients with stable coronary disease undergoing coronary artery bypass graft (CABG) surgery. Specifically, markers of oxidative stress and inflammation were compared in blood samples obtained from the atherosclerotic left anterior descending artery (LAD) and blood samples obtained from the healthy left internal thoracic artery (LITA), used as a bypass graft, within the same patient. Methods. Twenty patients scheduled for off-pump CABG were enrolled. Blood samples were collected from the LITA below anastomosis and the LAD below the stenosis. Samples were analysed for oxidative stress (sNOXdp, H2O2, NO) and inflammation markers (TNFα, IL-6, IL-1β, IL-10). Results. The analysis showed a significant increase in oxidative stress burden in the LAD as compared to LITA, as indicated by higher sNOX2-dp and H2O2 levels and lower NO levels (p < 0.01). Also, pro-inflammatory cytokines were increased in the LAD as compared to the LITA, as indicated by higher TNFα and IL-6 amounts (p < 0.01). On the other hand, no significant differences could be seen regarding IL-1β and IL-10 levels between the two groups. Conclusions. The oxidative stress and inflammatory burden are specifically enhanced in the LAD artery of stable coronary patients compared to systemic blood from the LITA of stable coronary patients.

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.

Ixodes ricinus ticks are ubiquitous in Europe, including in North-East Italy. These ticks are important vectors of several zoonotic pathogens of public health relevance. In this study, the habitat suitability range of I. ricinus ticks infected with zoonotic pathogens was predicted in North-East Italy, and relevant spatial predictors were identified. In 2015–2021, ticks were collected at 26 sampling sites in the study area. The collected ticks were screened for the presence of pathogens using PCR assays. For Borrelia, Rickettsia and Anaplasma/Ehrlichia species, data allowed for ecological niche modelling using Maxent. Environmental determinants potentially related to tick habitat suitability were used as model inputs. Predicted suitable habitat distributions revealed hotspots of the probability of pathogen presence in I. ricinus ticks mainly in the central and upper parts of the study area. Key environmental predictors were temperature, rainfall and altitude, and vegetation index for specific pathogens (Rickettsia and Anaplasma/Ehrlichia species). Increased risk of exposure to tick-borne pathogens upon tick bites in the predicted hotspot areas can, therefore, be expected. This provides useful information for public health risk managers in this and other similar regions.

Soil use and its proper management are key elements of sustainable development. However, given the complexity of the issue, it is necessary to address it using an interdisciplinary approach. The proposed work aims to analyze the consequences, in terms of damage assessment, of two different soil management systems of a cereal crop through the use of Life Cycle Assessment (LCA) methodology. One system follows a traditional approach and the other utilizes a Decision Support System (DSS). The long-term impacts on human health, ecosystems, and resource availability are calculated by employing the ReCiPe 2016 endpoint method. The results show notable reductions in resource use and environmental impacts with DSS, with a 41% decrease in damage to human health, a 24% reduction in ecosystem damage, and a 23% reduction in resource use. Hence, implementing new technologies and new management strategies in agriculture can lead to more sustainable management choices and can avoid long-term burdens compared to a traditional approach.

Cyclic-nucleotide phosphodiesterases (PDEs) represent a superfamily of enzymes playing a pivotal role in cell signaling by controlling cAMP and cGMP levels in response to receptor activation. PDE activity and expression are linked to many diseases including inflammatory diseases. In light of their specific biochemical properties, PDE inhibition has attracted the interest of several researrs In this context, PDE4 inhibition induces anti-inflammatory effects. Piclamilast and rolipram, well-known PDE4 inhibitors, are endowed with common side effects. The selective phosphodiesterase 4B (PDE4B) inhibitors could be a promising approach to overcome these side effects. In the present study, six potential PDE4B inhibitors have been investigated. Through this study, we identified three PDE4B inhibitors in human macrophages activated by lipopolysaccharide. Interestingly, two of them reduced reactive oxygen species production in pro-inflammatory macrophages.

Colorectal cancer (CRC) ranks third in terms of cancer incidence worldwide and is responsible for 8% of all deaths globally. Approximately 10% of CRC cases are caused by inherited pathogenic mutations in driver genes involved in pathways that are crucial for CRC tumorigenesis and progression. These hereditary mutations significantly increase the risk of initial benign polyps or adenomas developing into cancer. In recent years, the rapid and accurate sequencing of CRC-specific multigene panels by next-generation sequencing (NGS) technologies has enabled the identification of several recurrent pathogenic variants with established functional consequences. In parallel, rare genetic variants that are not characterized and are, therefore, called variants of uncertain significance (VUSs) have also been detected. The classification of VUSs is a challenging task because each amino acid has specific biochemical properties and uniquely contributes to the structural stability and functional activity of proteins. In this scenario, the ability to computationally predict the effect of a VUS is crucial. In particular, in silico prediction methods can provide useful insights to assess the potential impact of a VUS and support additional clinical evaluation. This approach can further benefit from recent advances in artificial intelligence-based technologies. In this review, we describe the main in silico prediction tools that can be used to evaluate the structural and functional impact of VUSs and provide examples of their application in the analysis of gene variants involved in hereditary CRC syndromes.

Purpose: We report the successful surgical treatment of a case of spontaneous complete anterior crystalline lens luxation in a patient affected by retinitis pigmentosa (RP), associated with elevated intraocular pressure and pupillary block. Additionally, we review the current literature regarding the association between ectopia lentis and RP. Case description: A 44-year-old female RP patient presented to our emergency department reporting severe ocular pain in her left eye (LE) and sickness. She had no history of ocular trauma and did not report systemic disorders. The best corrected visual acuity at presentation was 1/20 in her LE, the intraocular pressure was 60 mmHg, and slit lamp examination showed in her LE a complete dislocation of the lens in the anterior chamber, with mydriasis, atalamia, and a pupillary block. The patient had been administered intravenous mannitol 18% solution and dorzolamide–timolol eye drops and was hospitalized for urgent lens extraction. Anterior segment optical coherence tomography and ultrasound biomicroscopy were performed before surgery. Decompressive 23-gauge pars plana vitrectomy and phacoemulsification were performed, and the capsular bag was removed due to marked zonular weakness, with deferred intraocular lens implant. Conclusions: Acute angle closure glaucoma in patients with RP may be rarely caused by spontaneous anterior lens dislocation. To our knowledge, this is the first report of spontaneous anterior lens dislocation in an RP patient, documented through photographs, anterior segment optical coherence tomography, and ultrasound biomicroscopy.

An LC–Orbitrap–HRMS method was developed and validated for the simultaneous determination of four tetracyclines—oxytetracycline (OTC), tetracycline (TC), doxycycline (DC), and chlortetracycline (CTC)—in milk. This method involves sample extraction with McIlvaine–EDTA buffer solution (pH 4) and solid-phase extraction (SPE) with Oasis HLB cartridges, followed by the evaporation of the extract and its reconstitution with a 14% methanol aqueous solution before injection into the instrumental system. This method has been validated in terms of linearity, sensitivity, selectivity, precision, and accuracy, in accordance with Commission Decision 2002/657/EC requirements. Compared to existing methods, this approach optimally combines a quantitative procedure for extracting analytes from the milk of different species, including sheep, bovines, and goats, with a very short LC–Orbitrap–HRMS instrumental analysis time (only 8 min), simultaneously ensuring high precision, sensitivity, and applicability as a rapid confirmation method in official food control laboratories. The proposed method was applied to determine the concentration levels of OTC in milk samples derived from healthy Sardinian sheep and those naturally infected with Streptococcus uberis, after the intramuscular administration of an antibiotic, in order to evaluate how much of the drug was “subtracted” during penetration from blood into milk, with a potential effect of reducing its therapeutic efficacy.

Venomous marine gastropods of the superfamily Conoidea possess a rich arsenal of toxins, including neuroactive toxins. Venom adaptations might have played a fundamental role in the radiation of conoideans; nevertheless, there is still no knowledge about the venom of the most diversified family of the group: Raphitomidae Bellardi, 1875. In this study, transcriptomes were produced from the carcase, salivary glands, and proximal and distal venom ducts of the northeastern Atlantic species Raphitoma purpurea (Montagu, 1803). Using a gut barcoding approach, we were also able to report, for the first time, molecular evidence of a vermivorous diet for the genus. Transcriptomic analyses revealed over a hundred putative venom components (PVC), including 69 neurotoxins. Twenty novel toxin families, including some with high levels of expansion, were discovered. No significant difference was observed between the distal and proximal venom duct secretions. Peptides related to cone snail toxins (Cerm06, Pgam02, and turritoxin) and other venom-related proteins (disulfide isomerase and elevenin) were retrieved from the salivary glands. These salivary venom components may constitute ancestral adaptations for venom production in conoideans. Although often neglected, salivary gland secretions are of extreme importance for understanding the evolutionary history of conoidean venom.

Prostate cancer (PCa) is the third highest cause of cancer death in men. PCa is a very heterogeneous tumor form in terms of grade, phenotypes, and genetics, often accompanied by complex networks. PCa is characterized by slow growth that does not compromise the patient’s quality of life, unlike more aggressive forms showing rapid growth and progression. Early diagnosis, even for the most aggressive forms, increases the possibilities of cure with less aggressive treatments and fewer side effects. However, it is important to know how to decrease the exposure to modifiable risk factors, including diet, sedentary life, smoking and alcohol, can represent an effective tool to reduce the incidence of PCa. In addition, the chronic exposure to environmental factors, most of which act as endocrine disruptors, is the focus of recent studies for their potential role in promoting the onset and progression of PCa. Although molecular therapies and clinical trials for biomarker identification have been introduced into the management of PCa, these still lag behind research performed in other solid tumors. This review provides an overview of the modifiable factors of PCa, linked to lifestyle and environmental pollutants, which together with the development of new therapeutic targets, can reduce the incidence of PCa and improve the quality of life of patients.

Clear cell renal cell carcinoma (ccRCC) treatment has undergone three major paradigm shifts in recent years, first with the introduction of molecular targeted therapies, then with immune checkpoint inhibitors, and, more recently, with immune-based combinations. However, to date, molecular predictors of response to targeted agents have not been identified for ccRCC. The WHO 2022 classification of renal neoplasms introduced the molecularly defined RCC class, which is a first step in the direction of a better molecular profiling of RCC. We reviewed the literature data on known genomic alterations of clinical interest in ccRCC, discussing their prognostic and predictive role. In particular, we explored the role of VHL, mTOR, chromatin modulators, DNA repair genes, cyclin-dependent kinases, and tumor mutation burden. RCC is a tumor whose pivotal genomic alterations have pleiotropic effects, and the interplay of these effects determines the tumor phenotype and its clinical behavior. Therefore, it is difficult to find a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that could impact prognosis and response to specific treatment. To accomplish this task, the interpolation of large amounts of clinical and genomic data is needed. Nevertheless, genomic profiling has the potential to change real-world clinical practice settings.

Wheelchair basketball (WB) is an increasingly popular sport that guarantees numerous health benefits for people with disabilities who regularly practice it, such as an improved quality of life and psychophysical well-being. However, WB is a contact and high-stress sport, which exposes players to frequent overloads and injuries, mainly affecting the upper limbs. Therefore, shoulder pain (SP) is the most common musculoskeletal disorder among WB players, forcing them to suspend or abandon this sport activity. This narrative review aims to summarize all the known literature on this topic and to be a starting point for further research. Firstly, it explores the biomechanical causes that lead to SP and the underlying diseases, among which the most recurrent are rotator cuff tendinopathies. Furthermore, this overview deepens the most effective and specific rehabilitation programs for SP in WB players and it emphasizes the need for further studies to trial new rehabilitative protocols using novel technologies to make them faster and more personalized. In this regard, the general recommendation still remains to perform a combination of exercises such as strengthening, endurance and stretching exercises of various durations and intensities. To conclude, the most important prevention strategies are described, underlining the need for constant sport-specific training led by qualified personnel and suggesting some insights on possible new research aimed at improving wheelchair ergonomics, stressing the importance of a multidisciplinary team fully dedicated to the individual athlete.

Nowadays, the research in the fields of conservation and restoration is focusing on recording large amounts of data and information in order to obtain highly accurate surveys that include most details of constructions. Documenting and surveying are fundamental activities in achieving the successful preservation of cultural heritage, but also in implementing efficient strengthening interventions of structures. The applications of methods and techniques that link the disciplines of geometrical surveys and structural analyses are still fragmented, and further research is necessary to fully transfer site information into structural models. In this article, the authors propose a methodology with which to link different restoration fields, with the aim of highlighting the strengths and weaknesses of the interoperability between surveys (carried out through detailed restitution from point clouds), heritage building information modeling (HBIM), and structural analyses to connect three different disciplines. The goal is to find a synthesis model that brings together historical and geometric characteristics, but also physical–mechanical properties, for a structural evaluation through a finite element model (FEM). The case study of the Escuela José Mariano Méndez is analyzed, an extremely damaged historical adobe building in Santa Ana, the second largest city of El Salvador; it is considered fundamental to the national economy, particularly after the “coffee boom” in the late 1800s. The site, located near the historic center, is also known as “Antigua Escuela de Artes y Oficios” and embodies the architectural traditions of the region, being built in adobe and stone. Roma Tre University and the Secretaría de Cultura de la Presidencia (SECULTURA) are partners in this research project to document and restore the historical and cultural value of this site.