Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

This article focuses on the economic dimensions of maternal health, highlighting the benefits of investing in maternal healthcare and the policy implications for sustainable development. Through a comprehensive review of the literature, the article explores the economic impact of maternal health, including its effects on human capital, productivity, and healthcare costs. It emphasizes the importance of addressing social determinants such as access to healthcare services, education, employment, income, and geographical disparities. By prioritizing maternal health, societies can unlock the economic potential of women, promote inclusive growth, and reduce gender disparities. The article discusses policy interventions, including the importance of healthcare infrastructure, financial support for maternal healthcare, and promoting gender equality. It also emphasizes the need for future research to quantify the economic benefits and evaluate the cost-effectiveness of different interventions. Overall, the article underscores the economic imperative of investing in maternal health and provides valuable insights for policymakers and researchers seeking to enhance maternal health outcomes and promote sustainable economic development.

This study delves into the integration of Decentralized Finance (DeFi) within metaverses, probing its implications and potential. It elucidates DeFi protocols and the intricacies of metaverses before inspecting their intersection and the resulting economic prospects. The analysis further appraises inherent risks such as financial volatility, security, and regulatory issues. Case studies provide tangible insights into DeFi applications in metaverses. Future trajectories of DeFi in metaverses are projected, underlining the possible impact on the broader financial sector. This paper contributes to burgeoning research at the nexus of blockchain technology, finance, and virtual reality.

The insurance sector has undergone a transformative shift with the emergence of Insurtech, integrating technological innovations into the industry. This review aims to provide a comprehensive overview of the impact of Insurtech on the insurance sector, focusing on the case study of Lemonade. By placing the study in the context of the broader insurance landscape, the review explores the significance and relevance of this transformation. The article analyzes Lemonade's unique business model and its departure from traditional insurance practices. Furthermore, it examines the implications of Lemonade's approach on the industry and the challenges it faces. Through this analysis, the review sheds light on how Insurtech and the transformation of the insurance sector are redefining insurance services and consumer experiences. The future implications of these trends for insurance companies, consumers, and the industry as a whole are also explored. In summary, this review provides valuable insights into the transformative power of Insurtech, emphasizing the importance of technological advancements and innovative approaches in shaping the future of the insurance sector.

Barbera d'Asti - including Barbera d'Asti superiore - and Nizza are two DOCG (Denominazione di Origine Controllata e Garantita) wines produced in Piemonte (Italy) from Barbera grape variety. Differences among them arise in the production specifications in terms of purity, ageing and zone of production, in particular with concern to Nizza, which has more stringent rules and can therefore be considered as the one with the highest market value, with even three-fold more average prices. To guarantee producers and consumers, authentication methods must be developed in order to distinguish among the different wines. As the production zones totally overlap, it is important to verify whether the distinction is possible or not according to metals content, or whether chemical markers more linked to winemaking are needed. In this work, Inductively Coupled Plasma (ICP) elemental analysis and multivariate data analysis are used to study the authentication and traceability of samples from the three designations of 2015 vintage. The results show that, as far as elemental distribution in wine is concerned, work in the cellar, rather than geographic provenance, is crucial for the possibility of distinction.

This article offers an overview of congenital and acquired vascular anomalies involving the portal venous system in dogs and cats, as determined by multidetector-row computed tomography angiography. Congenital absence of the portal vein, portal vein hypoplasia, portal vein thrombosis and portal collaterals are described. Portal collaterals are further discussed as high- and low-flow connections, and categorized in hepatic arterioportal malformation, arteriovenous fistula, end-to-side and side-to-side congenital portosystemic shunts, acquired portosystemic shunts, cavoportal and porto-portal collaterals. Knowledge of different portal system anomalies helps understand the underlying physiopathological mechanism and is essential for surgical and interventional approaches.

Glioblastoma (GB), even though not frequent, is an extremely aggressive brain tumor, with a strong impact on patient outcomes, in terms of both length and quality of life. The protocol estab-lished by Stupp and coworkers in 2005, based on radiotherapy and temozolomide chemotherapy, after maximum safe surgical resection, remains the gold standard for GB treatment. However, it is evident nowadays that the extreme GB intratumoral and intertumoral heterogeneity, invasive-ness and recurrence are not compatible with a routinary and unfortunately uneffective treatment. In this review article, we summarize the principal challenging issues in finding new valuable therapies for GB and focus on the impact that extracellular vesicle (EV) research and exploitation can have in the field. EVs are natural particles delimited by a lipidic bilayer and full of functional cellular content, released and uptaken by cells as key means of cell communications. Moreover, being stable in body fluids, well-immunotolerated, able to cross physiological, inter-species, and inter-kingdom barriers, and to target specific cells, releasing inherent or externally loaded functionally active molecules, EVs can be potentially ideal allies in fighting GB and assuring to GB patients a better prognosis. Here we report the main results obtained until now, focusing on both EV sources and molecular cargo used in the different functional studies, mainly in vivo. Finally, we perform a SWOT analysis reporting both the main advantages and the pitfalls of developing EV-based GB therapeutic strategies to highlight the main directions to explore for realizing the promise of EV exploitation for GB treatment.

Abstract: The aim of this study was to evaluate the effects of solids accumulation on greenhouse gas (GHG) emissions, substrate, plant growth and performance of a horizontal flow (HF) treatment wetland (TW) planted with Phragmites australis (Cav.) Trin. ex Steud. sub sp. australis. The study was carried out in an eight-year-old full-scale HF-TW located in the Mediterranean region (Sicily, Italy). To collect data inside the HF unit, nine observation points (besides the inlet and the outlet) along three 8.5 m long transects (T1, T2, and T3) were identified. The first transect (close to the inlet zone) showed hydraulic conductivity (Ks) reduction of about one order of magnitude higher than the other two. Results highlighted GHG emissions increasing during the summer when temperature and solar radiation were higher than in the rest of the year. Carbon dioxide (CO2) emis-sions decreased from T1 to T3, with maximum monthly values in T1 (21.4 g CO2 m-2 d-1) about double with respect to T2 (12.6 g CO2 m-2 d-1) and T3 (10.7 g CO2 m-2 d-1) observed in July. The CO2 seasonal trend was similar to that of P. Australis growth. Theoretical me-thane (CH4) emissions followed the trend of volatile solids (VS), which was about 3.5 and 4 times in T1 to T2 and T3. The highest CH4 emissions in T1 were probably due to anaerobic bacteria (methanogens) that proliferated in the waterlogged, anoxic part of TW. The pore-clogging affected the chemical oxygen demand (COD) removal efficiency which de-creasing from T1 to T3 for the observation period. Notwithstanding this behaviour, the final effluent quality was very satisfactory with the average value of COD removal efficiency above 90%.

Uterine Tumor Resembling Ovarian Sex Cord Stromal Tumor (UTROSCT) is a rare uterine mesenchymal neoplasm, which resembles ovarian sex cord tumors of the ovary. Although, in general, UTROSCT exhibits benign behavior with a favorable prognosis, this neoplasm is nonetheless classified as being of an uncertain ma-lignant potential, given its low rate of recurrence and the fact that it rarely pro-duces metastases (lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous, lungs). Its histogenesis too is uncertain. Typically, UTROSCT oc-curs in peri-menopausal or menopausal women but can sometimes be observed in young women. Usually, this neoplasm can be found in the uterine corpus as a nodular intramural lesion, less frequently submucosal, subserosal or poly-poid/intracavitary. UTROSCT can cause abnormal bleeding, pelvic pain, enlarged uterus, mass sensation, but sometimes it is found purely by chance. This neo-plasm can be considered polyphenotypic on morphological, immunohistochem-ical, and genetic analyses. Generally, on microscopic examination, UTROSCT shows a predominant pattern of the cords, nests, and trabeculae typical of sex cord tumors of the ovary while, immunohistochemically, it is characterized by a co-expression of epithelial, smooth muscle, and sex cord markers. The aim of this review is to report clinical and pathological data and genetic alterations to estab-lish its impact on the prognosis and management of patients affected by this rare entity.

The past is an important lesson for facing the future with greater awareness. In this context, school plays a key role to spread knowledge on natural phenomena and to promote behavior change. Together with researchers, teachers can be strong allies to build more resilient future citizens. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) school training activities provide tools to get ready for the next earthquake and/or tsunamis. About 5000 students from both Middle schools (ISCED 2) and High schools (ISCED 3) were involved in active learning activities based on a flipped-up approach during special online scientific events in the Pandemic. Online lab activities were conducted respectively during the European Researchers’ Night (“Earthquakes: history teaches us the future: researchers for a day with experimentation in didactics for ESL”) and during the World Water Day 2021 and the World Earth Day 2021 (“Tsunamis: history teaches us the future researchers for a day with experimentation in didactics for ESL”). These two Episodes of Situated Learning (ELS) experiences triggered students’ interest, favoring remote learning, developing life skills, focusing on historical seismic studies of both past earthquakes and tsunamis.

Mesothelin is a protein that is expressed in the mesothelial cell lining in the pleura, peritoneum, and pericardium. The gene of mesothelin encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycophosphatidylinositol linkage and a shred fragment named the megakaryocytic-potentiating factor. The biological functions of this substance in normal cells are still unknown. Experimental studies on knockout mice suggest that this substance does not play an important role in development and reproduction. In contrast, it has been observed that mesothelin is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered a tumour marker or an antigenic target for many malignancies. Many molecular studies also have demonstrated that mesothelin is overexpressed in serous ovarian carcinomas and may bind to ovarian cancer antigen Ca-125, favouring the spread of the tumour in the abdominal cavity. 3 Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses as well as its impact on the prognosis in serous ovarian carcinomas. We also briefly discuss the latest progress of mesothelin-targeting therapies for this aggressive and lethal neoplasm.

The objective of this paper is to assess the potential for potable water savings due to rainwater use in a precast concrete factory in southern Brazil. The economic feasibility and the rainwater quality were also assessed. The current water consumption, future water demand and rainwater demand in the factory were estimated. The future demand considered was two times higher than the current water consumption since there are plans to increase the production. Three scenarios were then simulated using the computer programme Netuno. The ideal rainwater tank capacity, the potential for potable water savings and the economic feasibility analysis for each scenario were estimated. Samples of rainwater were collected in the factory and tested for quality for manufacturing precast concrete. For a rainwater tank capacity equal to 25,000 litres, the potential for potable water savings for the first scenario was 55.4%, but the first scenario was considered economically unfeasible. For the same tank capacity, the second and third scenarios presented viable results regarding potable water savings and payback. As for the rainwater quality, it was proven to be adequate for manufacturing precast concrete. The main conclusion is that rainwater can be used to manufacture precast concrete in the factory studied herein.

The study of hydrothermal travertines contributes to the understanding of the interaction between physico-chemical processes and the role played by microbial mats and biofilms in influencing carbonate precipitation. Three active travertine sites were investigated in Central Italy to identify the types of carbonate precipitates and the associated microbial mats at varying physico-chemical parameters. Carbonate precipitated fabrics at the decimetre- to millimetre-scale and microbial mats vary with decreasing water temperature: a) at high temperature (55-44°C) calcite or aragonite crystals precipitate on microbial mats of sulphide oxidizing, sulphate reducing and anoxygenic phototrophic bacteria forming filamentous streamer fabrics, b) at intermediate temperature (44-40°C), rafts, coated gas bubbles and dendrites are associated with Spirulina cyanobacteria and other filamentous and rod-shaped cyanobacteria, c) low temperature (34-33°C) laminated crusts and oncoids in a terraced slope system are associated with diverse Oscillatoriales and Nostocales filamentous cyanobacteria, sparse Spirulina and diatoms. At the microscale, carbonate precipitates are similar in the three sites consisting of prismatic calcite (40-100 µm long, 20-40 µm wide) or acicular aragonite crystals organized in radial spherulites, overlying or embedded within biofilm EPS (Extracellular Polymeric Substances). Microsparite and sparite crystal size decreases with decreasing temperature and clotted peloidal micrite dominates at temperatures &lt; 40°C, also encrusting filamentous microbes. Carbonates are associated with gypsum and Ca-phosphate crystals; EPS elemental composition is enriched in Si, Al, Mg, Ca, P, S and authigenic aluminium-silicates form aggregates on EPS. This study confirms that microbial communities in hydrothermal travertine settings vary as a function of temperature. Carbonate precipitate types at the microscale do not vary considerably, despite different microbial communities suggesting that travertine precipitation, driven by CO2 degassing, is influenced by biofilm EPS acting as template for crystal nucleation (EPS-mediated mineralization) and affecting the fabric types, independently from specific microbial metabolism.

In recent years, there has been a growing interest in utilizing natural antioxidants as alternatives to synthetic additives in food products. Apples and apple by-products have gained attention as a potential source of natural antioxidants due to their rich phenolic content. This review aims to provide a comprehensive overview of the antioxidant properties of apples and apple by-products, their extraction techniques as well as potential applications in food products because of their an-tioxidant or nutritional properties. The findings here reported highlights the proper utilization of apples and their by-products in food to reduce the detrimental effect on the environment and provide a positive impact on the economy.

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. In this study, we assessed the transcriptome by analyzing post-mortem mRNA extracted from the substantia nigra of individuals with PD and healthy controls. A total of 16,148 transcripts were identified, with 92 mRNAs displaying differential expression between PD and control groups. Specifically, 33 mRNAs were significantly upregulated, while 59 mRNAs were downregulated in PD compared to controls. The identification of statistically significant signaling pathways, with an adjusted p-value threshold of 0.05, unveiled noteworthy insights. Particularly, enriched categories included cardiac muscle contraction (involving genes such as ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), and cytochrome c oxidase subunit II (COX2)), GABAergic synapse (involving GABA type A receptor-associated protein like 1 (GABARAPL1), G protein subunit beta 5 (GNB5), and solute carrier family 38 member 2 (SLC38A2)), autophagy (involving GABARAPL1 and tumor protein p53-inducible nuclear protein 2 (TP53INP2)), and Fc gamma R-mediated phagocytosis (involving amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, including the involvement of cardiac muscle contraction and specific mitochondrial activity. This knowledge not only contributes to better diagnostic precision but also paves the way for the development of new targeted therapies.Keywords: mRNAs; RNA sequencing; Parkinson’s disease; transcriptome analysis; substantia nigra

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

Ocular pathologies present significant challenges in achieving effective therapeutic re-sults due to various anatomical and physiological barriers. Natural products, such as flavonoids, alone or in association with allopathic drugs, present many therapeutical actions, including anti-cancer, anti-inflammatory, and antibacterial action. However, their clinical employment is chal-lenging for scientists due to their low water solubility. In this study, we designed a liquid formu-lation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were de-termined by employing the SupraFit software on the Uv-vis titration experiment. A deep physical-chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it con-firmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility of 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), per-mitting the dissolution of the solid complex within 30 min. NMR studies revealed the involve-ment of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecu-lar modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains demonstrating a sig-nificant activity of the formulation to the free components.

The field of anesthesia has always been at the forefront of innovation and technology, and the integration of Artificial Intelligence (AI) represents the next frontier in anesthesia care. The use of AI and its subtypes such as machine learning has the potential to improve efficiency, reduce costs, and improve patient outcomes. AI can assist with decision-making, but its primary advantage lies in empowering anesthesiologists to adopt a proactive approach to address clinical issues. However, further research and validation are needed to fully understand the benefits and limitations of these applications in clinical practice. Moreover, the ethical implications of AI in anesthesia must also be considered to ensure that patient safety and privacy are not compromised. This paper aims to provide a comprehensive overview of AI in anesthesia, including its current and potential applications, and the ethical considerations that must be considered to ensure the safe and effective use of the technology.

Malaria is rare in Europe, but it is a medical emergency and programs for its control should ensure access to early diagnosis and prompt treatment within 24-48 h of the symptom’s onset. The consistent number of imported malaria cases and the risk of reappearance of autochthonous cases stimulated laboratories in non-endemic countries to evaluate diagnostic methods/algorithms: microscopy remains the gold standard, but with limitations. RDTs have greatly expanded the ability to diagnose malaria for rapid results due to simplicity and low cost, but they lack sensitivity and specificity. PCR-based assays provide more relevant information but need well-trained technicians. According to WHO global Technical Strategy for Malaria 2016-2030, the future direction for a rapid diagnosis is the development of Point-Of-Care Testing, which would be helpful for prompt/accurate treatment and for preventing the diseases spread. Despite the limitations of current diagnostic methods, they play important roles in dealing with the global malaria situation, including decreasing its incidence. Recently evidence suggested that Artificial Intelligence could be utilized for assisting pathologists in malaria diagnosis. Future studies need to be conducted to see whether this system can be used for routine malaria diagnostic procedures.

Background: Gender stereotypes and biases can influence perceptions of competence and suitability for certain medical specialties. Empathy is an important component of an optimal doctor-patient relationship. The scope of our study is to verify the correlation between “empathetic" behavioral style with attention and sensibility to the gender differences of patients of the medical students. Methods: An online survey was conducted using the Jefferson Scale for Empathy (JSE), to measure empathy in the context of health professions education and patient care; and the Nijmegen Gender Awareness in Medicine Scale (N-GAMS), which measures attitudes and assumptions about gender. A total of 234 students (52.1% M; mean age: 22.68±2.48) from Medicine and Surgery at the University of Salerno (Italy) participated, of whom n° 175 were third-year students and n° 59 were fifth-year students. Results: The JSE score shows that male students have higher scores (77.29±12.38) than females (75.91±10.39). Conversely, female students have higher perspective-taking (JSE Factor 1: Male= 51.26±11.84; Female= 52.72±11.88). In addition, third-year students are much more empathetic than their fifth-year colleagues (JSE Score: 3°ys= 77.35±11.46; 5°ys= 74.49±11.33). With reference to the GS, we found that male students have greater sensitivity than their female colleagues (GS: Male= 2.67±0.68; Female= 2.37±0.48); conversely, they have higher scores of gender stereotype towards patients (GRIP: Male= 2±0.88; Female= 1.59±0.61) and doctors (GRID: Male= 1.88±0.89; Female= 1.64±0.63). Also, the third-year students compared to their fifth-year colleagues are characterized by greater gender sensitivity (GS: 3°ys= 2.57±0.62; 5°ys= 2.42±0.57), less bias with respect to patients (GRIP: 3°ys= 1.77±0.79; 5°ys= 1.90±0.78) but, on the other hand, show more stereotypes and prejudices towards doctors (GRID: 3°ys= 1.77±0.81; 5°ys= 1.75±0.74). Conclusions: Humanistic attitudes, including empathy, should be instilled, and evaluated among trainees as an essential part of their postgraduate medical education.

Background and aim: Human Papillomavirus (HPV) is sexually transmitted, one of the three most common sexually transmitted infections (STIs) in both males and females, and the most common viral STI. A crucial public health strategy to protect people against HPV is through vaccination, which has shown its effectiveness in preventing HPV related diseases. Presently three types of vaccines are available (bivalent, quadrivalent, and nonavalent) and they all target at least the two most oncogenic virus genotypes (HPV 16, 18). In the past few years, the need to implement vaccination programmes that include all genders has been discussed in order to achieve herd immunity against HPV. To date, only a few countries have included young males in their vaccination programmes, so we aim through this review to provide an overview of the epidemiology of HPV and prevention strategies to prevent it, reporting the latest findings from the scientific literature.

Titanium and its alloys are used biomaterials for medical and dental applications, due to their mechanical and physical properties. The surface modifications of titanium with bioactive molecules can increase the osseointegration by improving the interface between the bone and implant. Titanium dioxide nanotubes (TiO₂NTs) have excellent bioactivity inducing cell adhesion, spreading, growth and differentiation. In this work, TiO₂NTs were functionalized with a lectin from the plasma of the fish Oreochromis niloticus aiming to favour the adhesion and proliferation of osteoblast-like cells, improving its biocompatibility. The TiO₂NTs were obtained by anodization of titanium and annealed at 400 °C for 3 h. The resulting TiO₂NTs were characterized by high-resolution scanning electron microscopy. The successfully incorporation of OniL on the surface of TiO₂NTs by spin coating was demonstrated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIE) and attenuated total reflection-Fourier transform infrared spectrum (ATR-FTIR). Our results showed that TiO₂-NTs were successfully synthesized in a regular and well-distributed way. The functionalization of TiO₂-NTs with OniL favoured adhesion, proliferation, and the osteogenic activity of osteoblast-like cells, suggesting its use to improve the quality and biocompatibility of titanium-based biomaterials.

Developing effective cognitive training tools for older adults, specifically addressing executive functions such as planning, is a challenging task. It is of paramount importance to ensure the implementation of engaging activities, which must be tailored to the specific needs and expectations of older adults. Furthermore, it is essential to provide the appropriate level of complexity for the planning task. A human-centred approach was employed to address the issues identified in the design of the tool. Two pilot studies were conducted with older adults to fine-tune the training task and optimise its suitability for them. This also led to an enhancement of the underlying planning engine, transitioning from simple fast-forward planner (PDDL4J) to an advanced heuristic search planner (ENHSP). The results show that conducting user studies enabled the development of a cognitive training system that gradually increases the proposed difficulty levels of the planning task while maintaining usability and satisfaction among older adults. This highlights the importance of conducting user studies when implementing cognitive training tools for older adults.

HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided into four families, HD-Zip I–IV. Phylogenetic and bioinformatics analysis of HD-Zip genes using transcriptomic and genomic datasets from a wide range of plant species indicate that the HD-Zip protein class was already present in green algae. Later, HD-Zips experienced multiple duplication events that promoted neo- and sub-functionalizations. HD-Zip proteins are known to control key developmental and environmental responses, and a growing body of evidence indicates a strict link between members of the HD-Zip II and III families and the auxin machineries. Interactions of HD-Zip proteins with other hormones such as brassinolide and cytokinin have also been described. However, it is striking that among the genes regulated by REV, a HD-Zip III protein playing a key role in apical development, are genes that mediate ABA signaling. Furthermore, HAT1 and HAT3, two HD-Zip II proteins involved in key developmental processes, repress ABA biosynthesis and signaling, indicating an essential role of these factors in adjusting development to changing environment.

The aim of this paper was to evaluate the changes in the mean bone density values of the midpalatal suture in 392 young patients treated with the Rapid Palatal Expander appliance according to sex, gender, vertical and sagittal skeletal patterns. Materials and Methods. The evaluations were performed using the low-dose protocol cone-beam computed tomography scans at t0 (preoperatively) and t1 (1 year after the beginning of the therapy). The region of interest was used to calculate bone density in Hounsfield units (HU) in the area between the maxillary incisors. Results. CBCT scan data of 196 females and 196 males (mean age of 11,7 years) showed homogeneous and similar density values of the MPS at T0 (547.59 HU - 565.85 HU) and T1 (542.31 - 554.20 HU). Class III skeletal individuals showed a significant higher BD than the II class group at T0, but not at T1. Females showed significantly higher BD than males at t0 and t1. No significant differences were found between the other groups and between two-time points in terms of bone density values of the MPS. Conclusions. Females and III class groups showed significantly higher bone density values than males and II class, respectively. No statistically significant differences were found from T0 to T1 in any groups, suggesting that a similar rate of suture reorganization occurs after the use of the RPE, following reorganization and bone deposition along with the MPS.

Non-small-cell lung cancer (NSCLC) is the second most common cancer worldwide, resulting in 1.8 million deaths/year. Most of the patients are diagnosed with a metastatic disease. Central Nervous System is one of the major metastatic sites. Brain metastases are associated with severe neurological symptoms, shorter survival and worst clinical outcomes. Brain radiotherapy and systemic oncological therapies are currently used for controlling both cancer progression and neurological symptoms. Brain radiotherapy includes stereotactic brain ablative radiotherapy (SBRT) or whole brain radiotherapy (WBRT). SBRT is applied for single or multiple (≤ 4) small lesions (&lt; 3 cm), while WBRT represents the best treatment choice in case of multiple and large brain metastases. In both cases radiotherapy application can represent an overtreatment causing severe toxicities without achieving a significant clinical benefit. So far, some scores have been proposed to define the potential clinical benefits derived from brain radiotherapy. However, most of them are not well validated into clinical practice. In this article, by presenting a clinical case of a patient with advanced NSCLC carrying a BRAFV600E mutation and brain metastases, we review the variables as well as the potential applicable scores to be considered in order to predict clinical outcomes and benefits from brain radiotherapy in patients with NSCLC and brain metastases.

Non-small-cell lung cancer (NSCLC) is the second most common cancer worldwide, resulting in 1.8 million deaths/year. Most of the patients are diagnosed with a metastatic disease. Central Nervous System is one of the major metastatic sites. Brain metastases are associated with severe neurological symptoms, shorter survival and worst clinical outcomes. Brain radiotherapy and systemic oncological therapies are currently used for controlling both cancer progression and neurological symptoms. Brain radiotherapy includes stereotactic brain ablative radiotherapy (SBRT) or whole brain radiotherapy (WBRT). SBRT is applied for single or multiple (≤ 4) small lesions (&lt; 3 cm), while WBRT represents the best treatment choice in case of multiple and large brain metastases. In both cases radiotherapy application can represent an overtreatment causing severe toxicities without achieving a significant clinical benefit. So far, some scores have been proposed to define the potential clinical benefits derived from brain radiotherapy. However, most of them are not well validated into clinical practice. In this article, by presenting a clinical case of a patient with advanced NSCLC carrying a BRAFV600E mutation and brain metastases, we review the variables as well as the potential applicable scores to be considered in order to predict clinical outcomes and benefits from brain radiotherapy in patients with NSCLC and brain metastases.

The study investigates the influence of road intersections on pedestrian accessibility in urban-rural fringe areas. An evaluation method to support planners and decision makers in the classification of crossing areas according to their effect on walking and in the prioritization of improvement interventions is proposed. In these peripheral parts of towns, pedestrians are almost ignored and people depend on car use for any necessity. Initiatives to improve livability can include the design of walkable friendly environments aiming at offering potential users good levels of security, comfort and convenience when walking to destinations. These spatial requirements have to be provided along road segments and even more on crossing areas which represent sensitive points of the entire connection system with a hindering influence on people’s propensity to walk. Starting with spatial basic interventions aiming at enhancing the continuity, safety and quality of pedestrian paths it is possible to reduce the physical and perceptual distance which separates fringe contexts from the rest of the city leading to a progressive integration of urban functions.

Numerous studies have shown the multiple benefits of plant biodiversity and the crucial role of resident’s awareness in conservation and land management. Plant biodiversity is investigated in an analytical monitoring report conducted jointly with local population engaged in livestock activities and the young residents who are shifting toward hospitality and tourism. The study area, covering over 800 km2 in Sardinia, is half forested and has landscape interest. During the research, genotypes of Quercus ilex L. with sweet acorns and richer in polyphenols were discovered, the oldest ecosystem services in those rural communities. Collaborative monitoring focused attention on the benefits of plants in different habitats: 53% of these have been known to livestock farmers as food for local breeds of goats and pigs; 15% are officinal and 13% endemic. They have also been used in human nutrition within the Mediterranean diet, and they have landscape and garden interest. The study analyzes numerical data from a critical and educational perspective. These data serve as indicators of ecosystem health for the purpose of sustainable management policies, and attest to collaborative monitoring as a tool for analyzing human activities and the necessary balance between profit and biodiversity conservation, given the current challenging climate change conditions.

Mitochondrial dysfunction plays a pivotal role in numerous complex diseases. Understanding the molecular mechanisms by which the “powerhouse of the cell” turns into the “factory of death” is an exciting yet challenging task that can unveil new therapeutic targets. The mitochondrial matrix protein CyPD is a peptidylprolyl cis-trans isomerase involved in the regulation of the permeability transition pore (mPTP). The mPTP is a multi-conductance channel in the inner mitochondrial membrane whose dysregulated opening can ultimately lead to cell death and whose involvement in pathology has been extensively documented over the past few decades. Moreover, several mPTP-independent CyPD interactions have been identified, indicating that CyPD could be involved in the fine regulation of several biochemical pathways. To further enrich the picture, CyPD undergoes several post-translational modifications that regulate both its activity and interaction to its clients. Here, we will dissect what is currently known about CyPD and critically review the most recent literature about its involvement in neurodegenerative disorders, focusing on Alzheimer’s Disease and Parkinson’s Disease, supporting the notion that CyPD could serve as a promising therapeutic target for the treatment of such conditions. Notably, significant efforts have been made to develop CyPD-specific inhibitors, which hold promise for the treatment of such complex disorders.

An outbreak of winter disease, complicated by severe respiratory syndrome, occurred in January 2020 in a high production dairy cow herd located in a hilly area of the Calabria region. Of the 52 animals belonging to the farm, 5 (9.6%) died with severe respiratory distress, death occurring 3-4 days after the appearance of the respiratory signs (caught and gasping breath). Microbiological analysis revealed absence of pathogenic bacteria whilst Real-time PCR identified the presence of RNA from Bovine Coronavirus (BCoV) in several organs: lungs, small intestine (jejunum), mediastinal lymph nodes, liver and placenta. Since being the only pathogen identified, BCoV was hypothesized to be the cause of the lethal pulmonary infection. Like the other CoVs, BCoV is able to cause different syndromes. Its role in calfhood diarrhoea and in mild respiratory disease is well known: we report instead the involvement of this virus in a severe and fatal respiratory disorder, with symptoms and disease evolution resembling that of Severe Acute Respiratory Syndromes (SARS).

Numerous new technologies have been implemented in image analysis methods that help researchers withdraw scientific conclusions from biological phenomena. Plants of the family Lemnaceae (duckweeds) are the smallest flowering plants in the world, and biometric measurements of single plants and their growth rate are highly challenging. Although the use of software for digital image analysis has changed the way scientists extract phenomenological data (also for studies on duckweeds), the procedure is often not wholly automated and sometimes relies on the intervention of a human operator. Such a constraint can limit the objectivity of the measurements and generally slows down the time required to produce scientific data. Here is the need to implement image analysis software with artificial intelligence that can substitute the human operator. In this paper, we present a new method to study the growth rates of the plants of the Lemnaceae family based on the application of machine learning procedures to digital image analysis. The method is compared to existing analogical and computer-operated procedures. Results showed that our method drastically reduces the time consumption of the human operator while retaining a high correlation in the growth rates measured with other procedures As expected, machine learning methods applied to digital image analysis can overtake the constraints of measuring growth rates of very small plants and might help duckweeds gain worldwide attention thanks to their great nutritional qualities and biological plasticity.

The decarbonization of the electricity grid as one among the actions to reduce fossil fuel emissions, and thus their impact on global warming in the future, will be achieved mainly via the integration and widespread diffusion of renewable power sources. This is going to be supported also by the shift from the paradigm production-transmission-distribution, where electricity production oversees large-size power plants, to renewable-based distributed/diffused production, where electricity is generated very close or even by the same (group of) user(s) (or prosumers in the latter case). The number of mid-/small-size installations based on renewable energy technologies will therefore increase substantially, and the related renewable generation will be dominant against that from large-size power plants. Unfortunately, this will reduce the reliability of the grid very likely, unless appropriate countermeasures are taken/implemented, hopefully at the same time the paradigm shift is being achieved. To this aim, it is important to identify the anomalies and main fault causes that might determine in renewable-based power systems. This paper surveys the current state-of-the-art on anomalies and faults affecting wind-PV-storage hybrid power systems, i.e., the main renewable technology ensemble that will establish the future grid, and highlights possible research directions that may help to fill the literature gaps.

The developmental phase of adolescence is characterized by a multitude of neurocognitive and psychosocial changes and is therefore considered one of the most critical developmental periods of life. Experimentation on the use of substances often begins in adolescence and so does the addiction process. Most research in human subjects shows that chronic cannabis abuse is the cause of the impairment of some cognitive functions, affecting the performance on divided attention, verbal memory and working memory. In this study, we wanted to investigate how the abuse of cannabis (chronic, occasional and absence use) can influence global cognitive functioning, also through executive functions. From the statistical analyzes of our study, it emerges that the group of subjects who use chronic cannabis (group 1) has a significant drop in working memory tasks compared to the group that does not use it (group 3). In addition, the goal of future studies by our group is to verify the permanent alteration of cognitive processes affected through revaluations with calendar follow-up (controlled).

The present review compared the efficacy of soft tissue substitutes (STS) and autogenous free gingival graft (FGG) or connective tissue graft (CTG) in mucogingival procedures to increase keratinized tissue (KT) width around teeth and implants. Two independent examiners performed the electronic search on Medline and Cochrane Library based on the following PICO’s format: (P) adult patients; (I) soft tissue substitutes and FGG/CTG; (C) STS vs CTG; STS vs FGG; STS vs CTR; (O) KT width gain; (S) Systematic Reviews, Randomized Controlled Trials. Results showed that around teeth, all biomaterials showed superior performance compared to CAF alone for treating gingival recessions. However, when compared to CTG, ADM yields the most similar outcomes to the gold standard (CTG), even though in multiple recessions CTG still continue to be considered the most favorable approach. Use of STSs (acellular matrix or tissue engineered) in combination with an apically positioned flap resulted in a significantly less gain of KTW compared to what achieved with FGG and APF. Around dental implants, free gingival grafts were deemed more effective than soft tissue substitutes in enhancing keratinized mucosa width.

The public administrations (PAs) that have joined the Covenant of Mayors must now complete their adaptation plans with the climate chapter (SECAP). At the same time, the previous Plan for sustainable energy (SEAP) was mainly dedicated to mitigation actions (sustainable energy). It was often managed directly by municipalities' in-house energy companies or agencies. The WMO1234 Recommendation (Guidance on Integrated Urban Hydrometeorological, Climate and Environmental Services) is a fundamental Guidance to allow PAs to make policies and decisions regarding city regeneration and population health prevention. The purpose of this manuscript is to describe a process undertaken in the Emilia-Romagna region to build a coherent frame from the individuation of local environmental vulnerabilities and adopt specific policies. This frame was created by the contribution of various Institutions, including the Regional Authority, which furnished the main directives and tools for the mitigation and adaptation, the Municipality of Bologna, which prepared the first Adaptation Plan following the SECAP guidance, the Emilia-Romagna branch of Italian Association of Municipalities (ANCI), which took in charge the approach to harmonize different urban contexts and to communicate with stakeholders and population, and Research Institutes and Scientific Associations to explore, with specific studies and modeling application, the outcomes produced by a joint support to the new urban directives, such as the General Urban Planning Plan (PUG). To achieve this result, the WMO Guidance 1234 has been assumed as a reference methodology to ensure the best utilization of available data and widespread a common science-based methodological approach to other municipalities.

Microbial-based biostimulants containing arbuscular mycorrhizal fungi (AMF), Trichoderma fungi and plant growth-promoting rhizobacteria (PGPR) have been applied in an open-field tomato cultivation. A two-years field experiment (2020-2021) was performed in Southern Italy on “Heinz 1534” processing tomato hybrid, using three commercial formulations characterized by different microbial consortia (MIC: Glomus spp., Rhizophagus spp., Bacillus spp., Streptomyces spp., Pichia spp., Trichoderma spp.; EKO: Glomus spp., Bacillus spp., Streptomyces spp., Pseudomonas spp., Arthrobotrys spp., Monacrosporium spp., Paecilomyces spp., Myrothecium spp., Trichoderma spp.; FID: Glomus spp., Bacillus spp., Trichoderma spp.) and comparing them to untreated control (CTRL). The effect of growing season and microorganism-based treatments on yield, technological traits and functional quality of tomato fruits was assessed. The year of cultivation (Y) affected yield (with lower fruit weight, higher marketable to total yield ratio and higher % of total defected fruits in 2020), and technological components (higher dry matter, total acidity, total soluble solids in 2020). During the first year of the trial, all evaluated treatments (MIC, EKO and FID) enhanced soluble solids content by 10%, on average, compared to CTRL. Sucrose and lycopene contents were influenced both by the microbial-based treatments and the growing season (greater values found in 2021 with respect to the first year). Y factor also significantly affected all evaluated metabolites contents, except for tyrosine, essential (EAA) and branched-chain (BCAAs) amino acids. Over two years of field trial, FID biostimulant enhanced the contents of proteins (+53.71%), alanine (+16.55%), aspartic acid (+31.13%), γ-aminobutyric acid (+76.51%), glutamine (+55.17%), glycine (+28.13%), monoethano-lamine (+19.57%), total amino acids (+33.55), essential amino acids (+32.56%) and branched-chain amino acids (+45.10%) compared to the untreated control. Our findings highlighted the valuable effect of FID microbial inoculant in boosting several primary metabolites (proteins and amino acids) in the fruits of processing tomato crop grown under Southern Italy environmental condi-tions, although no effect on yield and its components was appreciated.

Endocrine and nervous systems reciprocally interact to manage physiological individual functions and homeostasis. The nervous system modulates hormone release through the hypothalamus, the main cerebrally specialized structure of the neuroendocrine system. Indeed, it is involved in various metabolic processes, administering hormone and neuropeptide release at different levels. This complex activity is affected by neurons of various cerebral areas, environmental factors, peripheral organs, and mediators through feedback mechanisms. Therefore, neuroendocrine pathways have a key role in metabolic homeostasis control, and their abnormalities have been associated with the development of Metabolic Syndrome (MetS) in children. The impaired functioning of genes, hormones, and neuropeptides of various neuroendocrine pathways involved in several metabolic processes has been related to an increased risk of dyslipidaemia, visceral obesity, insulin resistance, type 2 diabetes mellitus, and hypertension. This review examines the neuroendocrine effects on the risk of MetS in children, identifying and underlying the several conditions associated with neuroendocrine pathway disruption. Neuroendocrine systems should be considered in the complex pathophysiology of MetS, and, when genetic or epigenetic mutations in "hot" pathways occur, they could be studied for new potential target therapies in severe and drug-resistant paediatric forms of MetS.

The use of natural stone has a historical and environmental value that makes it strategically valuable for landscape conservation in Europe. Marble, among others, is widely spread on Earth, and it offers high-performance features in architectural applications. However, the complexity of these formations and the rock variability in different ore bodies require detailed studies of the natural and induced stress state, the fracturing degree, and the influence of external factor (such as temperature and/or chemical agents) on the mechanical properties in order to optimize the exploitation processes by reducing extractive waste. This article shows a series of studies conducted by the authors over the last 20 years aimed at making the exploitation of marble blocks in the Carrara basin safer, more efficient, and, therefore, more sustainable. In particular, studies for increasing the knowledge on the natural and the induced stress state through on-site measurements and numerical modeling, studies to improve the quality of the exploited material through improvements of cutting technologies, studies to improve the knowledge of the mechanical behavior of the material under varying loads and temperature conditions and studies to improve the reuse of water materials and their reduction are reported.

Ranunculus asiaticus L. is an ornamental geophyte, mainly propagated by rehydrated tuberous roots. Vernalization before planting is a common practice to overcome the natural dormancy of tuberous roots, however little is known about the mechanisms underlying the plant response to low temperature. We investigated the influence of two hybrids, MBO and MDR, and three preparation procedures of tuberous roots, only rehydration (control, C), and rehydration plus vernalization at 3.5 °C for 2 weeks (V2) and for 4 weeks (V4), on plant growth, leaf photosynthesis, flowering and metabolism in plants grown in pot in unheated greenhouse. We reported the responses observed in the aerial part previously in this journal (Fusco et al., 2023). In this paper, we show changes in carbohydrate, amino acids, polyphenols and protein levels throughout the growing cycle, in the different plant stages: pre-planting, vegetative phase and flowering.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

The article delves into the landscape of the plant-based food industry, exploring innovative market entry strategies and their interplay with the evolving food market and shifting consumer preferences and lifestyles. Adopting a multidimensional approach, the study reflects diverse perspectives at play. Through a comparative analysis of strategic promotion and growth strategies employed by both innovative startups and established industry giants in the plant-based meat alternatives sector in Germany, the study aims to capture the challenges faced by the 'newer' wave of plant-based alternatives. This examination is particularly relevant for navigating the complexities of entering a competitive market. Striving to penetrate evolving consumer lifestyles, the study draws insightful comparisons with their "older" counterparts. In addition, through in-depth interviews with selected companies, the study investigates the entry methods of startups venturing into the German market, aiming to identify parallels and contrasts in market strategies with established brands. This provides valuable insights into innovation within the alternative food market. Furthermore, the study explores the process of brand "platformization" by scrutinizing the websites of the selected companies and analyzing customers' online reviews of their brand experience. This comprehensive analysis unveils distinctive patterns in communication strategies, brand positioning, and consumer engagement, offering insights into plant-based innovation shaping new, caring lifestyles.

Plants have evolved two opposing strategies in response to competition for light: shade tolerance and shade avoidance. To detect the presence of neighboring vegetation, shade-avoiding plants have evolved the ability to perceive and integrate multiple signals. Among them, changes in light quality and quantity are central to elicit and regulate the shade avoidance response. Here, we describe recent advances in the understanding of photoperception and downstream signaling mechanisms underlying the shade avoidance response, focusing on Arabidopsis because most of our knowledge derives from studies conducted in this model plant. Shade avoidance is an adaptive response, resulting in phenotypes with high relative fitness in natural dense communities. However, it contributes to reduction in crop plant productivity, and the design of new strategies aimed at attenuating shade avoidance in a stage- and/or organ- specific manner in high-density crop plantings is a major challenge for the future. For this reason, in this review, we also report on recent advances in the molecular description of the shade avoidance response in crops, such as maize and tomato, and discuss similarity and differences with Arabidopsis.

The residue of chestnut processing generates a large amount of waste material, a resource not adequately exploited. The phenolic composition of water extracts from discarded pericarp of four (MURG, LOCG, ILDP and COEV) chestnut accessions and one marron variety belonging to the Sardinian biodiversity was studied. The antioxidant capacity of cold and hot water extracts was determined by DPPH, ABTS and cyclic voltammetry tests. The antiproliferative effect on normal cells (fibroblasts), and colon (RKO and SW48), breast (MCF7) and melanoma (B16F10) cancer cells, was evaluated by biological assays. MTT test demonstrated that temperature and different extraction times significantly influenced the growth of cells, both normal and tumor. The fibroblast viability was significantly reduced by moderate doses of cold extracts, but only by doses greater than 250 µg/ml of hot extracts, regardless of the accession or cultivar. An even more marked effect was observed when RKO and SW48 were treated with cold extracts, while treatments on B16F10 melanoma cells resulted less effective. Differently, the cold extracts of all accessions induced a significant increase in MCF7 cell viability starting from moderate doses (50 µg/ml), whereas hot extracts had a similar, but less evident, effect compared to reference fibroblasts.

Pregnancy in women with Sickle Cell Disease (SCD) is a high-risk situation, especially during the third trimester of gestation and in the post-partum period, due to chronic hypoxia and vaso-occlusive phenomena occurring in the maternal-fetal microcirculation: as a result, unfavorable outcomes, such as intra-uterine growth restriction, prematurity or fetal loss are more frequent in SCD pregnancies. Therefore, there is a consensus on the need for a strict and multidisciplinary follow-up within specialized structures. Transfusion support remains the mainstay of treatment of SCD pregnancies, although most appropriate modalities are still controversial: the benefit of prophylactic management, either by simple transfusions or by automated Red Blood Cell Exchange (aRBCX), is not unanimously recognized. We illustrate the cases of three SCD pregnant patients who underwent aRBCX procedures at our institution in different clinical scenarios. Moreover, we carried out a careful literature revision to investigate the management of pregnancy in SCD, particularly regarding the practice of aRBCX. Our experience and current literature support using aRBCX in pregnancy as a feasible and safe procedure provided that specialized equipment and an experienced apheresis team are available. However, further research in this high-risk population, with appropriately powered prospective trials, will be desirable to refine indications and timing of aRBCX and confirm this approach's advantages on other transfusion modalities.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue with increased risk of fracture. The population that is most at risk for primary osteoporosis in-cludes post-menopausal women. Among different approaches, nutraceuticals are increasingly popular in developed countries since can contribute to bone health and can delay the onset of pathological bone loss. Our review covers three main aspects. Firstly, we discuss the current state of the two con-ditions, osteopenia, and osteoporosis. Secondly, we focus on the latest developments in natural Nutraceuticals and their effectiveness in reducing bone loss. Finally, we conduct a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis to examine the pros and cons of Nutraceuticals assumption. Nutraceuticals hold great promise, but we must address challenges such as regulatory control and experimental evidence to fully realize their potential. Other challenges include identifying the source of raw materials, ensuring the purity of the compound, avoiding contamination or the presence of other active compounds, maintaining product quality, and preventing interactions with other elements or drugs. By addressing these challenges, the scientific community can ensure more reliable indica-tions for the use of Nutraceuticals and help people lead healthier lives.

Volatile organic compounds (VOCs) are molecules present in our everyday life, and they can be positive, such as in the formation of odour and food flavour, or harmful for environment and humans, and the research is focusing on limiting their emissions. Various methods have been used to achieve this purpose. Firstly, we review three main degradation methods: activated carbon, photocatalysis and a synergetic system. We provide a general overview of the operative conditions and report the possibility of VOC abatement during cooking. Within the literature, none of these systems has ever been tested in presence of complex matrices, such as during a cooking process. The aim of this study is to compare the three methods in order to understand the behaviour of filter systems in the case of realistically complex gas mixtures. Proton Transfer Reaction - mass spectrometry (PTR-MS) has been used as real-time monitoring of volatilome. Since VOC emissions are highly dependent on the composition of the food cooked, we evaluated the degradation capacity of the three systems for different burger types (meat, greens and fish). We demonstrate pros and cons of the photocatalysis and adsorption and how a combined approach can mitigate the drawbacks of photocatalysis.

Hydrotalcites (HTlc) represents a class of nanostructured layered materials that may be employed in a variety of applications, from green to bio technologies. In this paper, we report an investigation on HTlc made of Mg and Fe, recently employed to improve the growth in vitro of osteoblasts within a keratin sponge. We have carried out an analysis of powder materials and of HTlc dispersed in keratin and spin-coated on a Si/SiO2 substrate at different temperatures. A DC magnetic study of the powders has been carried out with a Quantum Design Physical Property Measurement System, equipped with a Vibrating Sample Magnetometer. The data gathered prove that these HTlc are fully paramagnetic, and keratin shows a very small magnetic response. Optical and Atomic Force Microscopy analyses of the thin films provide a detailed picture of clusters randomly dispersed in the films with various dimensions. The magnetic properties of these films have been characterized using the Nano Magneto Optical Kerr Effect (NanoMOKE) down to 7.5K. The data collected show that the local magnetic properties can be mapped with a micrometric resolution distinguishing HTlc regions from keratin ones. This approach opens new perspectives in the characterization of these composite materials.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

the close phylogenetic relationship between ascidians (Tunicata) and vertebrates makes them a powerful model for studying the innate immune system. To better understand the nature and dynamics of immune responses and the mechanisms through which bacterial infections are detected and translated into inflammation in Ciona robusta, we applied an approach combining in vivo lipopolysaccharide (LPS) stimulation, immune-labelling and functional enzymatic analyses. The immunohistochemistry showed that toll-like receptor 4 (TLR4) and nuclear factor kappa B (NFκB) were expressed during the inflammatory pharynx response 4 hours post-LPS, with formation of immune-stained haemocyte nodules in the vessel lumen. Pharynx vessel endothelium also took part in the inflammatory response. Observations of histological sections from naive and MS-inoculated ascidians confirmed immuno-positive tissue response. Enzyme immune parameters – which included the activity of phenoloxidase, glutathione peroxidase, lysozyme, alkaline phosphatase and esterase – showed up-modulation 4 hours after LPS injection, confirming their involvement during ascidian inflammatory response. These findings provide new insights into the mechanisms involved in LPS-induced C. robusta response and suggest that a broad innate immune mechanism is involved in the regulation of tunicate inflammatory responses.

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the key regulator of low-density lipoprotein cholesterol (LDL-C) plasma levels. We previously observed that treatment of dyslipidemic subjects with nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) (LopiGLIK®) did not alter the plasma PCSK9 levels. Thus, the aim of the present study was to investigate the effect of these three components on PCSK9 expression in HepG2 cell line in relationship to their effects on LDL-C cellular uptake. HepG2 cell line were incubated with Berberis aristata cortex extract (BCE), red yeast rice (RYR) and Morus alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (WB and ELISA assays), PCSK9 mRNA and its promoter activity. BCE (40 µg/mL) reduced PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent inhibition of PCSK9 at mRNA and protein levels, with a maximal reduction at 1 mg/mL; no significant changes in PCSK9 promoter activity were found. MLE also downregulates the expression of fatty acid synthase and HMG-CoA reductase mRNA levels. The combination of RYR, BCE and MLE reduced PCSK9 at mRNA, protein, and promoter activity. Finally, this combination induced the LDL receptor and LDL-C uptake by HepG2 cells. In conclusion, the positive effect of MLE on PCSK9 supports the rational of using this nutraceutical combination to control hyperlipidemic conditions.

To live in the information society means to be surrounded by billions of electronic devices full of sensors that constantly acquire data. This enormous amount of data must be processed and classified. A solution commonly adopted is to send these data to server farms to be remotely elaborated. The drawback is a huge battery drain due to high amount of information that must be exchanged. To compensate this problem data must be processed locally, near the sensor itself. But this solution requires huge computational capabilities. While microprocessors, even mobile ones, nowadays have enough computational power, their performance are severely limited by the Memory Wall problem. Memories are too slow, so microprocessors cannot fetch enough data from them, greatly limiting their performance. A solution is the Processing-In-Memory (PIM) approach. New memories are designed that are able to elaborate data inside them eliminating the Memory Wall problem. In this work we present an example of such system, using as a case of study the Bitmap Indexing algorithm. Such algorithm is used to classify data coming from many sources in parallel. We propose an hardware accelerator designed around the Processing-In-Memory approach, that is capable of implementing this algorithm and that can also be reconfigured to do other tasks or to work as standard memory. The architecture has been synthesized using CMOS technology. The results that we have obtained highlights that, not only it is possible to process and classify huge amount of data locally, but also that it is possible to obtain this result with a very low power consumption.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Background. Pregnancy rates in women on dialysis have increased in the last decades, thus making it a topic of growing interest. The rarity of this event is predominantly due to fertility problems and to the high rates of pregnancy failure including stillbirth, fetal and neonatal deaths [1]. Methods. We conducted a narrative review of existent literature in order to analyse the major issues about pregnancy on dialysis to give the reader a full updated prospective about this topic which, even if not common, is becoming more and more frequent. Results. Even if recently acquired knowledge has improved diagnosis and treatment of dialysis pregnancies focusing on several aspects, pregnancy on dialysis remains a great challenge for obstetricians and should be managed by a multidisciplinary expertise team. Conclusion. Dialysis in pregnancy may be necessary for women previously affected by end stage renal disease (ESRD) becoming pregnant, or in case of acute renal injury presenting for the first time during gestation or, again in case of existent renal pathology worsening during pregnancy and requiring dialysis. Although some evidence suggests that more intensive dialysis regimens are correlated with better obstetric outcomes, the optimal therapeutic protocol still remains to be established.

The aim of this literature review was to present the novel imaging modalities elastography and contrast-enhanced ultrasonography. We provided an overview of the concepts and applications of each technique for the investigation of neoplastic and metastatic tumors in dogs and cats. Studies with elastography are based on the elasticity and deformation of the evaluated tissue. The information obtained from the different types of elastography can aid in the detection and differentiation of malignant and benign structures. Descriptions of elastographic studies in several organs and tissue in veterinary medicine reported that, in general, malignant tumors tend to be more rigid, and, therefore, less deformable than benign lesions or in comparison to the healthy parenchyma. Contrast-enhanced ultrasonography is based on the intravenous injection of contrast media constituted by microbubbles. This imaging modality can be performed in non-sedated animals and provides information on the tissue perfusion, allowing the investigation of macro- and micro-circulation. Studies with different organs and tissues were performed in dogs and cats and revealed a tendency of malignant tumors to present faster transit of the contrast media (time to wash-in, peak and wash-out). These advanced techniques can be associated with other imaging modalities, aiding important information to the well-established exams of B-mode and Doppler ultrasonography. They can be used as screening tests, potentially representing an alternative to the invasive sampling methods required for cytological and histopathological analysis.

The time required to reach a correct diagnosis is one of the most important problems for rare disease (RD) patients. Diagnostic delay can be intolerably long, to the point that it is usually described as a “diagnostic odyssey” and, sometimes, a diagnosis might never occur. The International Rare Disease Research Consortium proposed, as ultimate goal for 2017-2027, to enable all people with a suspected RD to be diagnosed within one year if the disorder is known, and to enter a globally coordinated diagnostic and research pipeline for the unsolved cases. In-depth analysis of the genotype through next generation sequencing, together with a standardized in-depth phenotype description and sophisticated high-throughput approaches, have been applied as diagnostic tools to increase the chance of a timely and accurate diagnosis. This approach is very fruitful as, according to the Orphanet database, from 2010 to March 2017 more than 600 new RDs have been described and about 3600 genes linked to RDs have been identified. However, combination of -omics and phenotype data and international sharing of this information raise ethical concerns. Values to be assessed include not only patient autonomy but also family implications, beneficence, non-maleficence, justice, solidarity and reciprocity, which must be respected and promoted and, at the same time, balanced among each other. In this work we suggest that, to maximise patients involvement in the search for a diagnosis and identification of new causative genes, undiagnosed patients should have the possibility to: 1) actively participate in the description of their phenotype; 2) choose the level of visibility of their profile in matchmaking databases; 3) express their preferences regarding return of new findings, in particular which level of Variant of Unknown Significance (VUS) significance should be considered relevant to them. The quality of the relation between individual patients and physicians, and between the patient community and the scientific community is critically important for making the best use of available data and combining efforts in the search for matches with similar cases worldwide that will help to solve unsolved cases. The contribution of patients to collecting and coding data comprehensively is critical for efficient use of data downstream of data collection.

Abstract: Abnormal growth of oligodendrocyte precursor cells (OPCs) importantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-methoxyestradiol (2ME), an endogenous tubulin interacting metabolite of estradiol is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions it is undergoing phase II clinical trials. We hy-pothesize that 2ME may prevent glioma growth by targeting OPC growth. Here we tested this hypothesis by assessing the impact of 2ME on growth of OPC cell line “Oli-neu” and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentra-tion-dependent manner and accompanied with significant upregulation in expression of p21 and p27, negative cell cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater 2ME induced apoptosis with increased expression of caspase 3, PARP and caspase-7 fragments, externalized phosphatidylserine staining / apopercentage and increased mitochondrial activity. Flow-cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2 and p53 expres-sion as well as OPC cell fusion, key mechanisms driving endoreduplication or whole-genome duplication. Importantly, inhibition of p53 with pfithrin-α rescued 2ME-induced endoreduplica-tion. The pro-apoptotic and endoreduplication actions of 2ME were accompanied with upregula-tion of survivin, cyclin A, Cyclin B, Cyclin D2, ppRB. Taken together our findings provide evi-dence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs in a survival - fight or flight mode leading to endoreduplication. This inherent survival character-istic of OPCs may, in part be responsible for drug resistance in gliomas as observed for many tubulin interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on cell-cycle status of the individual cells. Combining tubulin-interfering molecules with drugs, such as pfithrin-α, that inhibit endoreduplication may help inhibit OPC/glioma growth and lim-it drug resistance.

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

The 2021/2022 influenza season was not characterised by a well-defined incidence peak. A high value of incidence was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N=940) in a population of central Italy during the 2021/2022 season. A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.

Black soldier fly larvae (BSFL) can use food by-products or residues as a growth substrate, and their use is considered a strategic solution to improve the sustainability and efficiency of animal production. BSFL need to be reared under controlled environmental conditions, as temperature can affect the welfare of the larvae and the efficiency of their bioconversion. The goal of this experiment was to test different diets: control, vegetable, carnivorous, omnivorous and to assess their effect on larval growth performance, chemical composition, and substrate temperature. BSFL (6-days-old) were randomly selected and allocated to one of the four diets for the entire experiment (8 days). The temperature in each container was measured twice daily using a thermal imaging camera. The vegetable diet led to significantly lower growth performance (p

Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Mutations leading to aberrant APC splicing have rarely been reported. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM_000038.5: c.1621_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Moreover, we performed a literature me-ta-analysis of APC splicing mutations. We found that 123 unique APC splice site mutations, in-cluding the one described here, have been reported in FAP patients, 69 of which have been char-acterized at the mRNA level. Among these, only a small proportion (9/69) results in an in-frame protein, with 4 mutations causing skipping of exon 12 and/or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and 5 mutations leading to skipping of exon 5, 7, 8, and (partially) 9 with loss of regions not encompassing known functional domains. The APC splicing mutations considered in this study cluster with the AFAP phenotype and delineate a novel molecular mechanism of pathogenesis in FAP disease.

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.

For their clinical use Mesenchymal Stromal Cells (MSCs), isolated from bone marrow (BM-MSCs) are considered Advanced Therapy Medicinal Products (ATMP) and need to be produced according to Good Manufacturing Practice (GMP). Human platelet lysate (HPL) represents a good GMP-compliant alternative to animal serum and after pathogen inactivation with Psoralen was more efficient and safer to produce MSCs in GMP. In this study MSCs cultivated in FBS (FBS-MSC) or inactivated HPL (iHPL-MSC), were compared for their immunomodulant properties. In particular, the effects of MSCs on: 1)proliferation of total Lymphocytes (Ly) and on naïve T Ly subsets induced to differentiate versus Th1 and Th2 Ly; 2) the immunophenotype of different T cell subsets; 3)the cytokine release to verify Th1, Th2 and Th17 polarization were analyzed by using in vitro co-culture system. We observed that iHPL-MSCs showed the same immunomodulant properties observed in the FBS-MSCs co-cultures. Although, a more efficient effect on the increase of naïve T cells and, in the Th1 cytokine release related to iHPL was observed. This study confirms that iHPL, used as medium supplement, may be considered a good alternative to FBS for a GMP-compliant MSC expansion to preserve their immunomodulant proprieties.

Capturing atmospheric CO2 and storing it in natural rock systems (i.e., alkaline earth silicate and hydroxide minerals) through carbonation reactions is a promising greenhouse gas mitigation research, and largely depends on the use of hydrated ultramafic rocks (serpentinites), which are widespread in orogenic belts around the globe. The Jurassic ophiolites in the Southern Apennines represent a natural analogue and a great opportunity for the mineralogical sequestration of CO2. Serpentinites of the Pollino ophiolite Massif have been widely studied for their mineralogical, petrographic, and chemical characteristics, providing major findings on their impact on environmental and human health issues. Serpentinites here have been divided into cataclastic and massive types based on their structures and are characterized by pseudomorphic and vein textures. The mineralogy of the studied serpentinites consists of lizardite, antigorite, clino-crysotile, Cr-chlorite, magnetite, tremolite, actinolite, pyroxene and calcite, and the most commonly occurring serpentine minerals are polymorphs of serpentine including lizardite, clino-crysotile and antigorite. Systematic petrographic and mineralogical studies of serpentinites in ophiolites, such as those outcropping in the Southern Apennines can represent a starting point for the study of natural materials, which can be used for CO2 storage and sequestration. A particular attention must be given to those carbonate phases, produced by carbonation processes to check whether the serpentinites of the Pollino Massif can be used for the induced mineral Carbon Capture Storage (CCS). If successful, this technique and the Pollino Massif serpentinites can become highly significant in safeguarding the health of our planet's climate.

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Background: Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the most important competencies developed during the first 3 years of life through the interaction of the child with people, objects, events, and other environmental factors. The main goal of our study is to evaluate the relationship between digital devices use and language abilities in children between 8-36 month, considering also the influence of several variables. Materials and Methods: We conducted a cross-sectional observational study on 260 healthy children (140 males = 54%) aged between 8-36 months (mean=23.5±7.18 months). All the parents completed a self-report questionnaire investigating the use of digital devices by their children, and a standardized questionnaire for the assessment of language skills (MacArthur). Multiple linear regression was used to evaluate the relationship between different variables. Subsequent moderation analysis were performed to verify the influence of other factors. Results: W found a statistically significant negative correlation between the total daily time of exposure to digital devices and the Actions and Gestures Quotient (ß=-0.397) in children between 8-17 months, and between the total daily time of exposure to digital devices and Language Quotient (ß=-0.224) in children between 18-36 months. Sex, level of education/job of parents, modality of use/content of digital device do not significantly affect these relationships. Conclusion: In our study we found that a longer time of exposure to digital devices was related to lower mimic-gestural skills in children from 8-17 months and to lower language skills in children between 18-36 months, regardless of age, sex, socio-economic status, content and modality of use. Further studies are needed to confirm and better understand this relationship, but parents and pediatricians are advised to limit the use of digital devices by children and encourage the social interaction to support the learning of language and communication skills in this age group.

Chlorhexidine digluconate (CHX) has shown the ability to significantly reduce inflammation and marginal bone loss (MBL) at 1-year follow-up but limited data exists regarding its long-term efficacy in peri implant stability. The objective was to compare the long-term effects of a placebo gel (16 patients in Group A) or a 0.20% CHX gel (15 patients in Group B) used at each previous surgical and prosthetic stage. Follow-ups were conducted in 2022, investigating by biological, radiological, clinical, mechanical evaluation the long-term effects. Data were statistically analyzed. The research achieved a 96.7% implant success rate over five years, but 41.9% of patients didn't attend annual oral hygiene check-ups. The average MBL was 1.04 ± 0.39 mm, with no significant differences between the two groups. Notably, patients who attended regular periodontal check-ups experienced significantly less MBL than those who didn't (p &lt;0.05). At five years, the effects of CHX were reduced, with both groups showing moderate bone loss. The results suggest early disinfection could enhance both short and long-term outcomes. In fact, patient with initial minor MBL preserve this advantage also at 5 years of follow-up. Additionally, the data underscore the importance of annual check-ups in early detection and management of biological and mechanical complications.

The assessment of an organization/product's environmental footprint is based on the protocols developed by the Joint Research Centre of the European Union, which take into account 16 impact categories. Among the categories covered are toxicity to freshwater ecosystems and to humans. Standard protocols use only chemical parameters as input data, preventing the true impact of entire complex mixtures, such as emissions discharged into the environment, from being determined. Biological assays allow us to bridge this gap: in the current study, assays were used to determine baseline toxicity towards aquatic organisms (green algae, luminescent bacteria, and crustaceans) as well as specific toxicity (mutagenicity and carcinogenicity). Expected impacts were compared using two approaches (standard and bioassay-centered results obtained are not always in line and, in general, the traditional method underestimates impacts). This demonstrates the importance of these assays and suggests that they be used in LCA (Life Cycle Assessment) protocols as well.

Abstract: The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC “cassettes”, each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the gamma-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5’ end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner.

Background and Objectives: Since the protective role of ghrelin against high glucose-induced retinal damage was not yet explored, we aimed to investigate the serum levels of total ghrelin (TG), its acylated (AG) and des-acylated (DAG) forms in diabetic retinopathy (DR) patients. Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels, enhancing the risk of microhemorrhages, was investigated; Materials and Methods: Serum markers were determined by Enzyme-Linked Immunosorbent Assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with non-proliferative (NPDR) and 15 patients with proliferative DR (PDR); Results: TG and AG serum levels were significantly decreased in NPDR (P &lt; 0.01 vs Diabetic) and in PDR patients (P &lt; 0.01 vs NPDR). AG serum levels were inversely associated with DR progression (r = -0.83,P &lt; 0.01), serum neutrophils percentage (r = -0.74, P &lt; 0.01) and serum NE levels (r = -0.73, P &lt; 0.01). These were significantly increased in NPDR (P &lt; 0.01 vs Diabetic) and PDR (P &lt; 0.01 vs PDR) groups, positively correlating with DR progression (r = 0.86, P &lt; 0.01). Conclusions: The reduction of circulating AG and its association with the increased risk of microhemorrhages could be considered a novel marker for DR progression.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Background: The level of food processing has gained interest for a potential determinant of human health. The aim of this study was to assess the relation between level of food processing and prostate cancer severity. Methods: A sample of 120 consecutive patients were examined for their dietary habits assessed through validated food frequency questionnaires, their dietary intake of food groups categorized according to the NOVA classification, and the severity of prostate cancer according to the European Association of Urology (EAU) guidelines groups risk. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest. Results: Individuals reporting higher consumption of unprocessed/minimally processed foods were less likely to have worse prostate cancer severity than lower consumers in the energy-adjusted model [odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17-0.84, P = 0.017 and OR = 0.33, 95% CI: 0.12-0.91, P = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusted for potential confounding factors, the association was no more significant (Table 4). A borderline association was also found between higher consumption of UPF and worse prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998-4.44; P = 0.051), but again the association was no more significant after adjusting for the other covariates. Conclusions: The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

According to several evidence, forest environmental seems able to provide beneficial effects on functional and psychological parameters, related to cardiovascular, metabolic, respiratory functions as well depression and anxiety. The aim of this study is to investigate the effect of a one-day forest walking in Selva di Castelfidardo (AN, Italy) on 37 participants aged 21-68, most of them living in either urban or suburban areas of large cities. We observed a statistically significant effect on sympathovagal balance by the means of heart rate, systolic and diastolic blood pressure, body temperature, skin temperature, skin conductance, HRV parameters (AVNN, SDNN, rMSSD, pNN50, LF, HF, LF/HF ratio), oxygen oximetry, PEF, FEV1. A significant difference was also detected on the Perceived Stress Scale responses (19.27 pre vs 13.81 post-immersion, p=<0,05; -28,3% variation). Our data contribute to increase the body of literature about the effect of forest walking, adding data on an Italian area qualified for forest bathing.

High-frequency neuroelectric signals like electroencephalography (EEG) or magnetoencephalography (MEG) provide a unique opportunity to infer causal relationships between local activity of brain areas. While causal inference is commonly performed through Classical Granger causality (GC) based on multivariate autoregressive models, this method may encounter important limitations (e.g. data paucity) in the case of high dimensional data from densely connected systems like the brain. Additionally, physiological signals often present long-range dependencies which commonly require high autoregressive model orders / number of parameters. We present a generalization of autoregressive models for GC estimation based on Wiener-Volterra decompositions with Laguerre polynomials as basis functions. In this basis, the introduction of only one additional global parameter allows to capture arbitrary long dependencies without increasing model order, hence retaining model simplicity, linearity and ease of parameters estimation. We validate our method in synthetic data generated from families of complex, densely connected networks and demonstrate superior performance as compared to classical GC. Additionally, we apply our framework to studying the directed human brain connectome through MEG data from 89 subjects drawn from the Human Connectome Project (HCP) database, showing that it is able to reproduce current knowledge as well as to uncover previously unknown directed influences between cortical and limbic brain regions.

Leptospirosis is a zoonotic disease that poses a significant threat to human and animal health worldwide. Among different animal species, pigs are known to play a crucial role in the transmission of the pathogenic Leptospira spp. This study aimed to investigate the prevalence of Leptospira spp. infection and associated risk factors in subsistence pig production in the state of Paraná, Brazil. A total of 1393 serum samples were collected from pigs on 188 subsistence properties in different regions of the state, and tested using the microscopic agglutination test (MAT) to detect antibodies against 24 different Leptospira spp serovars. The results revealed an overall seroprevalence of 68.78% for Leptospira spp. antibodies, with Icterohaemorrhagiae, Butembo, and Pomona being the most commonly detected serovars. Poor housing conditions, lack of rodent control, absence of veterinary assistance, and a history of reproductive problems were identified as significant risk factors associated with Leptospira spp. infection in the subsistence pig population. These findings highlight the urgent need for implementing effective control measures, such as improved housing conditions, rodent control, and veterinary assistance, to prevent the spread of this zoonotic disease in subsistence pig production systems in Paraná, Brazil.

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

Recreational water activities are widely recognized to have a positive impact on our physical and mental well-being. However, recreational water sources and their management are also a risk factor for human health, due to different agents, including the overgrowth of cyanobacteria and algae. These organisms have the potential to metabolize organic matter and produce thermophilic and thermotolerant toxins. Different species of algae participate in biofilm formation and impact on maintenance of equipment for water treatment. We reviewed the state of the art by providing basic definitions, taxonomy and the epidemiological and clinical issues related to the recreational uses of waters. Methods for treatments and monitoring are summarized, considering both traditional and innovative strategies. Public health and surveillance perspectives impose to focus on the detection of toxins, the formation of biofilms, the understanding of the benthonic and planktonic components as part of a larger microbial biodiversity.

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. A proper delivery of probiotics or their metabolites (i.e., post-biotics) can avail itself of biomaterial encapsulation by innovative manufacturing technologies. This review paper aims at providing the most recent biomaterial-assisted strategies proposed to treat infections or disbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal to target different tissues and suit diverse therapeutic opportunities. Hydrogels, and in particular polysaccharides, are the focus of this review, as they have been reported to better sustain vitality of the live cells incorporated. Specifically, the approaches for fabricating hydrogel-based devices with increasing dimensionality (D), namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds) endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and post-biotic release were reported.

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily-adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymphnode oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI / LINAC n. 23748). Patients with oligometastatic lymphnodes from PCa treated with daily-adaptive MR-guided SBRT on 1.5T MR-linac were included in the study. Minimum required follow-up of 3 months after SBRT. Primary end-point was local progression-free survival (LPFS). Secondary end-points were: nodal progression-free survival (NPFS), and progression-free survival (PFS), and toxicity. Results: 118 lymphnode oligometastases from PCa were treated with daily-adaptive 1.5T MR-guided SBRT in 63 oligometastatic patients. 63.5% patients were oligoprogressive and 36.5% oligoprogressive. Two-year LPFS was 94.5%. Median NPFS was 22.3 months, and the 2-year NPFS was 46.5%. Having received hormone therapy before SBRT was correlated with lower NPFS at the multivariate analysis (1-y NPFS 87.1% versus 42.8%; p= 0.002 - HR 0.199, 95% CI 0.073-0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than the oligoprogressive state. Median PFS was 10.3 months, the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p= 0.01 - HR 0.259, 95% CI 0.117-0.574). No acute and late toxicities occurred during treatment. Conclusion: the present is the largest prospective study of 1.5T lymphnode SBRT on MR-linac in patients with PCa. Lymphnode SBRT by 1.5T MR-linac provides high local control rates with an excellent toxicity profile.

Electrospinning is known to be an effective and straightforward technique to fabricate polymer non woven matrices made of nano and microfibers. Micro patterned morphology of electrospun matrices results to be outmost advantageous in the biomedical field, since it is able to mimic extracellular matrix (ECM), and favors cell adhesion and proliferation. Controlling electrospun fibers alignment is crucial for the regenerative purposes of certain tissues, such as neuronal and vascular. In this study we investigated the impact of electrospinning process parameters on fiber alignment in tubular nanofibrous matrices made of Poly (L-lactide-co-ε-caprolactone) (PLA-PCL); a Design of Experiments (DoE) approach is here proposed in order to statistically set up the process parameters. The DoE was studied keeping constants the previously set material and environmental parameters; voltage, flow rate and mandrel rotating speed were the process parameters here investigated as variables. Orientation analysis was based on ImageJ and plugin Orientation J analysis of SEM images. The results show that voltage combined with flow rate has significant impact on electrospun fiber orientation, and the greatest orientation is achieved when all the three input parameters (voltage, flow rate and mandrel rotation speed) are at their maximum value.

The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures, have contributed to the emergence of drug-resistant bacteria, which can spread at the human-animal-environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a "One Health" approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is one of the most controversial diseases in pediatric rheumatology. Despite its first description being published more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine re-lease in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

Bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and similarly to the other cetaceans represent the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary and expression study of Tursiops truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged TRA and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the CDR-IMGT of the dolphin variable V alpha and beta domains were identified. According to comparative modelisation, the atome pair contact sites analysis between the human MH1 grove (G) domains and the TR V domains confirms conservation of the structure of the dolphin TR/pMH.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

BACKGROUND: Probiotics may prevent the allergic response’s development due to their anti-inflammatory and immunomodulatory effects. The aim of this study is to determine if the prophylactic treatment with a mixture of Bifidobacterium animalis subsp. Lactis BB12 and Enterococcus faecium L3, would reduce symptoms and need for drug use in children with allergic rhinitis (AR). METHODS: The study included 250 children aged from 6 to 17 years, affected by AR. Patients were randomly assigned to the intervention group (117) or to the placebo group (86). Patients of the intervention group, in addition to conventional therapy (local corticosteroids and/or antihistamines), were treated, in the 3 months preceding the development of AR symptoms, with a daily oral administration of a probiotic mixture containing the Bifidobacterium animalis subsp Lactis BB12 DSM 15954 and the Enterococcus faecium L3 LMG P-27496 strain. Nasal Symptoms Score(NSS) was used to evaluate AR severity before and after the treatment with probiotics or placebo. RESULTS: 96% of the patients in the intervention group showed a significant decrease in their NSS after the probiotic treatment as well as a decrease in the intake of pharmacological therapy. GPower software was used to calculate the test power. Given the probability of error α = 0.05, the total sample size n = 117 and the effect size ρ = 2.0651316, the power of the test is 1 - β = 1. CONCLUSIONS: When administered as a prophylactic treatment the mixture of BB12 and L3 statistically decrease signs and symptoms of AR and reduces significantly the need of drugs.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

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

Adipose tissue-derived stem cells (ADSCs) represent a subset of mesenchymal stem cells in every adipose compartment throughout the body. ADSCs can differentiate into various cell types, including chondrocytes, osteocytes, myocytes, and adipocytes. Moreover, they exhibit a notable potential to differentiate in vitro into cells from other germinal lineages, including endothelial cells and neurons. ADSCs have a wide range of clinical applications, from breast surgery to chronic wounds. Furthermore, they are a promising cell population for future tissue-engineering uses. Accumulating evidence indicates decreased proliferation and differentiation potential of ADSCs with increasing age, body mass index, diabetes mellitus, metabolic syndrome, or exposure to radiotherapy. Therefore, recent literature thoroughly investigates this cell population's senescence mechanisms and how they can hinder their possible therapeutic applications. This review will discuss the biological mechanisms and the physio-pathological causes behind ADSC senescence and how they can impact cellular functionality. Moreover, we will examine the possible strategies to invert these processes, re-establishing the full regenerative potential of this progenitor population.

Opuntia sp. contain antioxidant phytochemicals resistant to ROS damage, whose excess negatively affect fertilization. We investigate the activity of fruit extracts of O. dillenii and O. ficus indica (cv red and yellow) on sperm quality and cryopreservation. In the first experiment, we exposed the samples to extracts (50 µl) for 1 hour to then evaluate semen parameters (vitality, motility, acrosome reaction, DNA fragmentation and oxidative stress). The results showed a significant increase in the motility (86%±0.19 for OFI cv yellow, 82%±0.15 for OFI cv red and 90%±0.08 for O. dillenii) compared to the control (80%±0.17). Moreover, we noted a reduction of DNA fragmentation on treated (3%±0.03 in OFI cv yellow, 7%±0.09 in OFI cv red and 5%±0.07 in O. dillenii) than the control (40%±0.14). Furthermore, the oxidative stress was reduced after exposure to solutions (3.15mV in the control and 2.94mV in the treated). In the second experiment, 50 µl of solutions were added to the Freezing medium. After thawing, we observed an improvement in vitality and the number of intact acrosomes. Our results suggest that Opuntia sp. fruit extracts improve sperm quality, both before and after cryopreservation, optimizing the potential of fertilization of sperm cells.

The benthic matrix acts as a key natural archive where the memory of long-term timescale environmental changes is recorded. Some ecological and chemical features of fjord sediments were explored during the AREX cruise carried out in the Svalbard archipelago in summer 2021. The activity rates of the enzymes leucine aminopeptidase (LAP), beta-glucosidase (GLU) and alkaline phosphatase (AP) and community-level physiological profiles (CLPP) were studied with the aim of determining the functional diversity of the benthic microbial community, while bacterial isolates were screened for their susceptibility to antibiotic molecules in order to explore the role of these extreme environments as potential reservoirs of antibiotic resistance. Enzyme activity rates were obtained by fluorogenic substrates, CLPP by Biolog Ecoplates; antibiotic susceptibility assays were performed through the standard disk diffusion method. Spatial trends observed in the functional profiles of the microbial community suggested the variability in the microbial community composition, presumably related to the patchy distribution of organic substrates. Complex Carbon sources, carbohydrates and amino acids were the organic polymers preferentially metabolized by the microbial community. Multiple resistance to ampicillin, clindamycin and gentamycin was detected in all the sampled sediments, excepting in the southern Hornsund area, stressing the role of sediments as a potential reservoir of chemical wastes ascribable to antibiotic residuals. This study provides new insights on the health status of fjord sediments of West Spitsbergen applying a dual ecological and biochemical approach. Microbial communities in the fjord sediments showed globally a good functional diversity, suggesting their versatility to rapidly react to changing conditions.

Skin cancer is a disease that reflects most malignant neoplasms worldwide, whose rate of involvement has increased significantly in recent decades. Treatments that offer efficient results with attenuation of adverse reactions and greater patient compliance have been the subject of many systematic investigations. This review aims to qualitatively present published works that showed new strategies to increase the penetration power of natural substances through the skin in the topical treatment against skin cancer. In this sense, nanoengineering mechanisms, the iontophoresis technique, and photodynamic therapy using natural products (NP) contribute to new knowledge about substance carrier strategies in topical treatments against skin cancer.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.