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Vincenzo Vestuto,1,* Marisa Conte,1,* Mariapia Vietri,1,* Francesca Mensitieri,2 Valentina Santoro,1,3 Anna Di Muro,1 Mariaevelina Alfieri,4 Maria Moros,5,6 Maria Rosaria Miranda,1,3 Chiara Amante,1 Matteo Delli Carri,1 Pietro Campiglia,1 Fabrizio Dal Piaz,2,7 Pasquale Del Gaudio,1 Nunziatina De Tommasi,1,3 Antonietta Leone,1 Ornella Moltedo,1 Giacomo Pepe,1,3 Elisa Cappetta,1 Alfredo Ambrosone1 1Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy; 2Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 84081, Italy; 3National Biodiversity Future Center (NBFC), Palermo, 90133, Italy; 4Clinical Pathology, Santobono-Pausilipon Children’s Hospital, AORN, Naples, 80122, Italy; 5Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 7Operative Unit of Clinical Pharmacology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, 84131, Italy*These authors contributed equally to this workCorrespondence: Alfredo Ambrosone; Elisa Cappetta, Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy, Email aambrosone@unisa.it; ecappetta@unisa.itPurpose: Extracellular vesicles (EVs) are promising tools for nanomedicine and nanobiotechnology. The purification of mammalian-derived EVs involves intensive processes, and their therapeutic application raises multiple safety and regulatory issues. Plants have the potential to serve as nonconventional sources of therapeutically relevant EVs. In this context, we recently identified hairy roots (HRs) of medicinal plants as a novel biotechnological platform to produce EVs for human health.Methods: Herein, we report the purification, omics profiling, and bioactivity of EVs isolated from HRs of the medicinal plants S. sclarea and S. dominica. EVs were isolated from conditioned media of HR cultures using differential ultracentrifugation (dUC) and size exclusion chromatography (SEC). The isolated EVs were characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The proteomic and metabolomic profiles of the EVs were determined using mass spectrometry. Uptake studies and bioactivity assays, including confocal microscopy, MTT, flow cytometry, ROS quantification, and untargeted metabolomics analyses, were conducted in SH-SY5Y cells treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to evaluate the therapeutic potential of EVs in an in vitro model of Parkinson’s disease.Results: S. sclarea HRs released nanosized round-shaped EVs with a distinctive molecular signature. HR EVs from S. sclarea and S. dominica revealed conserved cargo of secondary metabolites, predominantly triterpenoids, which are known for their antioxidant properties. We showed that HR EVs are safe, enter the cells, and strongly inhibit apoptosis in a cellular model of Parkinson’s disease. Cellular metabolomics revealed that EVs preserved metabolic homeostasis and mitigated cellular oxidative stress when co-administered with 6-OHDA. Mechanistically, HR EVs inhibited 6-OHDA autoxidation and substantially reduced the accumulation of its oxidative products, which are responsible for 6-OHDA-induced toxicity.Conclusion: Collectively, our findings provide compelling evidence that EVs isolated from the hairy roots of Salvia species are promising, non-mammalian alternative for the design of novel therapies targeting neurological disorders. Keywords: non-mammalian EV source, Salvia extracellular vesicles, hairy roots, nanomedicine, neuroprotection, Parkinson’s disease

The uterine tourniquet is often not used to reduce intraoperative blood loss due to controversial opinions in the literature. The objective was to evaluate the effectiveness of this procedure in laparotomic myomectomy. This is a retrospective, monocentric case-control study, including patients who underwent laparotomic myomectomy and were categorized into the Tourniquet Group (A) and No Tourniquet Group (B). The blood loss outcomes were compared. Intra-operative blood loss in Group A was 275 ± 200 mL, while in Group B was 410 ± 390 mL (p = 0.11). Notably, five patients in the No Tourniquet Group lost more than 1000 mL of blood and required blood transfusion, while no such cases were reported in the Tourniquet Group. Furthermore, the decrease in hemoglobin post-procedure was statistically significant, favoring Group A with a decrease of 1.9 ± 0.7 g/dL compared to Group B’s 2.8 ± 2.2 g/dL (p = 0.04). The use of the Foley catheter as a tourniquet during laparotomic myomectomy may represent a remarkable tool that profoundly impacts the surgical process by substantially reducing blood loss. Its use may play a role in significantly diminishing the likelihood of requiring blood transfusions, enhancing patient safety and outcomes, and should be systematically adopted.

IntroductionThe current investigation presents a two-fold approach to rediscovering the potential of Sonchus asper as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of S. asper, thus enhancing economic profits.MethodsLiquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves. The antioxidant activity, the hypoglycaemic effect and the incorporation into liposomes were evaluated.Results38 compounds and 6 essential amino acids were identified. The incorporation into liposomes maximized the health-promoting properties for potential pharmaceutical or food applications.DiscussionThe commercialization of S. asper could: (i) contribute to improving the well-being of rural and urban communities, being S. asper a wild edible plant available at low cost, environmentally friendly, resilient, and adaptable; (ii) generate landowner economic returns.

Introduction: Ovarian cancer (OC) exhibits an aggressive behavior, wherein the therapeutic approach always involves both surgery and chemotherapy. Survival outcomes are still related to comprehensive surgical excision of all macroscopic lesions (Rauh-Hain et al., 2017), increasing gynecologic oncologists’ efforts to achieve the highest possible complete resection rate (Tozzi et al., 2024). The peritoneum serves as both a dissemination pathway and a barrier that restricts tumor spread beyond its confines. This understanding has prompted the adoption of en-bloc resection strategy for the entire pelvis, involving the removal of pelvic organs along with the surrounding peritoneum. The en-bloc pelvic resection procedure allows for the removal of pelvic disease in all cases of advanced ovarian cancer (Tozzi et al., 2017).Endeavors should be also directed towards minimizing surgical morbidity, by the adoption of minimally invasive surgery for debulking procedures (Tozzi et al., 2023). Case: This video demonstrates a laparoscopic en-bloc pelvic resection with creation of an end-to-end transanal anastomosis. The surgical specimen extraction and the placement of the anvil were performed through the vaginal route.A 75 year-old patient presented with FIGO stage IIIC OC with a 12 cm pelvic mass involving the whole pelvis. The patient was enrolled in the ULTRA-LAP trial and underwent laparoscopic primary debulking surgery with en-bloc pelvic resection. No protective ileostomy was performed and bowel opening occurred on the fifth postoperative day. The patient was discharged on the 11th postoperative day, thereafter completing a regimen of 6 cycles of carboplatin and paclitaxel chemotherapy. Conclusions: The en-bloc resection of the pelvis is a standardized procedure that consists of ten reproducible steps.

Diabetes is one of the most common diseases worldwide, with an increasing number of people affected. Insulin therapy is still the major treatment for both Type 1 and Type 2 diabetes and has evolved from bulky syringes to modern insulin pens introduced in 1985. An insulin pen consists of three major parts: a cartridge, a single-use pen needle (PN), and a precision dosing mechanism. Initially, PNs were long and thick, causing great discomfort and concern. Thanks to advances in design, shorter and thinner needles have appeared on the market, improving patient acceptability and pain perception. Studies highlight the influence of PN geometry and other characteristics on injection-related pain, including length, diameter, bevel design, and hub. Despite a lack of specific international regulations for PN geometry, scientific publications have focused on exploring different PNs’ characteristics to optimize patient comfort and reduce pain. To guide the selection of suitable PNs, this review provides a round-up of literature research findings on the impact of PN geometry on pain perception and patient acceptability. Specifically, it provides an overview of the PN manufacturing process, current international regulations, and the state-of-the-art research on PN geometry affecting pain perception.

Spatially disordered but uniformly distributed point patterns characterized by so-called blue-noise long-range spatial correlations are of great benefit in computer graphics, especially in spatial dithering thanks to the spatial isotropy. Herein, the potential photonic properties of blue-noise disordered, homogeneous point processes based on farthest-point optimization are numerically investigated for silicon photonics. The photonic properties of blue-noise two-dimensional patterns are studied as a function of the filling fraction and benchmarked with photonic crystals with a triangular lattice. Ultrawide and omnidirectional photonic band gaps spanning most of the visible spectrum are found with estimates of gap–midgap ratios of up to 55.4% for transverse magnetic polarization, 59.4% for transverse electric polarization, and 32.7% for complete band gaps. The waveguiding effect in azimuthal defect lines is also numerically evaluated. These results corroborate the idea that long-range correlated disordered structures are helpful for engineering novel devices with the additional degree of freedom of spatial isotropy, and capable of bandgap opening even without total suppression of infinite-wavelength density fluctuations.

Abstract Purpose Radiofrequency ablation is an increasingly used surgical option for ablation, resection and coagulation of soft tissues in joint arthroscopy. One of the major issues of thermal ablation is the temperature monitoring across the target areas, as cellular mortality is a direct consequence of thermal dosimetry. Temperatures from 45 °C to 50 °C are at risk of damage to chondrocytes. One of the most reliable tools for temperature monitoring is represented by fiber optic sensors, as they allow accurate and real-time temperature measurement via a minimally invasive approach. The aim of this study was to determine, by fiber Bragg grating sensors (FBGs), the safety of radiofrequency ablation in tissue heating applied to ex-vivo bovine hip joints. Methods Ex vivo bovine hips were subjected to radiofrequency ablation, specifically in the acetabular labrum, for a total of two experiments. The WEREWOLF System (Smith + Nephew, Watford, UK) was employed in high operating mode and in a controlled ablation way. One optical fiber embedding seven FBGs was used to record multipoint temperature variations. Each sensor was 1 mm in length with a distance from edge to edge with each other of 2 mm. Results The maximum variation was recorded in both the tests by the FBG1 (i.e., the closest one to the electrode tip) and was lower than to 2.8 °C. The other sensors (from FBG2 to FBG7) did not record a significant temperature change throughout the duration of the experiment (maximum up to 0.7 °C for FBG7). Conclusions No significant increase in temperature was observed at any of the seven sites. The sensor nearest to the radiofrequency source exhibited the highest temperature rise, but the variation was only 3 °C. The minimal temperature increase registered at the measurement sites, according to existing literature, is not expected to be cytotoxic. FBGs demonstrate the potential to fulfil the strict requirements for temperature measurements during arthroscopic surgery.

IntroductionThe development of agriculture in terms of sustainability and low environmental impact is, at present, a great challenge, mainly in underdeveloped and marginal geographical areas. The Salvia rosmarinus “Eretto Liguria” ecotype is widespread in Liguria (Northwest Italy), and farmers commonly use it by for cuttings and for marketing. In the present study, this ecotype was characterized in comparison with other cultivars from the same geographical region and Campania (Southern Italy), with a view to application and registration processes for the designation of protected geographical indications. Moreover, the possibility of using the resulting biomass after removing cuttings or fronds as a source of extracts and pure compounds to be used as phytosanitary products in organic farming was evaluated. Specifically, the potential of rosemary extracts and pure compounds to prevent soft rot damage was then tested.MethodsA targeted NMR metabolomic approach was employed, followed by multivariate analysis, to characterize the rosemary accessions. Bacterial soft rot assay and disk diffusion test were carried out to evaluate the activity of extracts and isolated compounds against Pectobacterium carotovorum subsp. carotovorum. Enzymatic assay was performed to measure the in vitro inhibition of the pectinase activity produced by the selected pathogen. Molecular docking simulations were used to explore the possible interaction of the selected compounds with the pectinase enzymes. Results and DiscussionThe targeted metabolomic analysis highlighted those different geographical locations can influence the composition and abundance of bioactive metabolites in rosemary extracts. At the same time, genetic factors are important when a single geographical area is considered. Self-organizing maps (SOMs) showed that the accessions of “Eretto Liguria” appeared well characterized when compared to the others and had a good content in specialized metabolites, particularly carnosic acid. Soft rotting Enterobacteriaceae belonging to the Pectobacterium genus represent a serious problem in potato culture. Even though rosemary methanolic extracts showed a low antibacterial activity against a strain of Pectobacterium carotovorum subsp. carotovorum in the disk diffusion test, they showed ability in reducing the soft rot damage induced by the bacterium on potato tissue. 7-O-methylrosmanol, carnosol and isorosmanol appeared to be the most active components. In silico studies indicated that these abietane diterpenoids may interact with P. carotovorum subsp. carotovorum pectate lyase 1 and endo-polygalacturonase, thus highlighting these rosemary components as starting points for the development of agents able to prevent soft rot progression.

In this paper, we perform a comparative analysis of business models used by Energy Service Companies (ESCOs), suitable for the deployment of energy efficiency measures in the commercial rented sector across Europe. These models can effectively contribute to solving the split-incentive issue that arises in the rented building scenario. Some of them are obtained from their “traditional” counterparts, which do not consider the rented scenario, but just a bipartite agreement between an Energy Service Company and its client. The EU Horizon 2020 project SmartSPIN (Smart energy services to solve the SPlit INcentive problem in the commercial rented sector) targets delivery of enhanced energy services for commercial rented sector. These enhanced energy services (a) combine demand management services and energy efficiency interventions, (b) facilitate the adoption of renewables, (c) optimize the balance between demand and supply, (d) alleviate the split incentive issue. The pilot implementation of SmartSPIN is in progress in a business park in Greece, in an office building in Ireland and in two shopping centers in Spain. Key recommendations toward the implementation of such a smart energy service are provided in this paper. They have been obtained from a detailed analysis of ten interviews of key stakeholders of the energy efficiency sector and of the commercial rented sector, along with an analysis of a selection of the most relevant technical literature. This paper argues that the classical shared savings and guaranteed savings ESCOs models may be adapted to the commercial rented sector and used at SmartSPIN’s demonstration sites in Spain, Greece and Ireland. The guaranteed savings model appears to be the most appropriate one to use when the building owner is funding the energy efficiency project using own funds or liaising directly with a bank or other finance provider. The validation method for the comparative analysis of business models and selection of the most appropriate one is based on both literature review and consultation of selected stakeholders’ (stakeholder value creation framework).