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Abstract Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients’ osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia.

Background: Distal pancreatectomy (DP) is a well-established minimally invasive procedure. However, feasibility and technical details when using Versius robotic surgical system are still unexplored. Method: This is a prospective stage 2a development IDEAL (Idea, Development, Exploration, Assessment and Long-term monitoring) case series. All consecutive robotic DP (RDP), including both splenectomy (DPS) and spleen-preserving DP (SPDP), were analysed. Pre- intra- and post-operative details were prospectively recorded. Results: 6 DPS and 3 SPDP were performed between May 2022 and May 2024. Conversion to open was recorded in one case. The average operating time and robot docking time were 185 ​min (range: 118–300) and 9.3 ​min (range: 3–15), respectively. No reoperation or 90-days mortality were recorded. Ports placement, instruments used, and surgical strategy are described in detail. Conclusion: We present the first series on RDP performed by Versius robotic surgical system. The procedure is safe and feasible, and careful patient selection is required for the first cases.

The global impact of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in 2019–2020 has led to significant changes in worldwide vaccination and immune prophylactic approaches. In this study, our research delves into a new immunization strategy that does not involve the use of additional adjuvants or preservatives, focusing on the effects of virus fusion with a bacterial nanostructure. The experimental procedures outlined in this paper involved the cultivation of SARS-CoV-2, the production, extraction, and nanocharacterization of outer membrane vesicles (OMV) from Neisseria meningitidis, immunization of mice with two doses of OMV combined with SARS-CoV-2, and the use of mesoporous silica SBa15 and SBa16 adsorbed to the same virus. The immune response was assessed through an indirect elisa method, analysis of cytokine expression profiles, and seroneutralization of the SARS-CoV-2 strain. The characterizations of associated OMV - SARS-CoV-2 and adsorption SBa15 and SBa16 were performed using Nanosight Tracking Analysis (NTA), which showed a high density of particles in the formulation. mice were then immunized, resulting in an immune response that produced high levels of neutralizing antibodies in IgG and IgG1 mouse immunoglobulins. In addition, expressions of IL-2, IL-4, and IL-23 in spleen cells were reinforced after the vaccination process. The comparative study of these three vaccine formulations has shown that the development of new vaccines for SARS-CoV-2 should take into consideration the production of neutralizing antibodies and the maintenance of immunological memory.

ABSTRACT Infections with multidrug-resistant bacteria pose a major healthcare problem which urges the need for novel treatment options. Besides its potent antiplatelet properties, ticagrelor has antibacterial activity against Gram-positive bacteria, including methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). Several retrospective studies in cardiovascular patients support an antibacterial effect of this drug which is not related to its antiplatelet activity. We investigated the mechanism of action of ticagrelor in Staphylococcus aureus and model Bacillus subtilis, and assessed cross-resistance with two conventional anti-MRSA antibiotics, vancomycin and daptomycin. Bacillus subtilis bioreporter strains revealed ticagrelor-induced cell envelope-related stress responses. Sub-inhibitory drug concentrations caused membrane depolarization, impaired positioning of both the peripheral membrane protein MinD and the peptidoglycan precursor lipid II, and it affected cell shape. At the MIC, ticagrelor destroyed membrane integrity, indicated by the influx of membrane impermeable dyes, and lipid aggregate formation. Whole-genome sequencing of in vitro-generated ticagrelor-resistant MRSA clones revealed mutations in genes encoding ClpP, ClpX, and YjbH. Lipidomic analysis of resistant clones displayed changes in levels of the most abundant lipids of the Staphylococcus aureus membrane, for example, cardiolipins, phosphatidylglycerols, and diacylglycerols. Exogeneous cardiolipin, phosphatidylglycerol, or diacylglycerol antagonized the antibacterial properties of ticagrelor. Ticagrelor enhanced MRSA growth inhibition and killing by vancomycin and daptomycin in both exponential and stationary phases. Finally, no cross-resistance was observed between ticagrelor and daptomycin, or vancomycin. Our study demonstrates that ticagrelor targets multiple lipids in the cytoplasmic membrane of Gram-positive bacteria, thereby retaining activity against multidrug-resistant staphylococci including daptomycin- and vancomycin-resistant strains.IMPORTANCEInfections with multidrug-resistant bacteria pose a major healthcare problem with an urgent need for novel treatment options. The antiplatelet drug ticagrelor possesses antibacterial activity against Gram-positive bacteria including methicillin-resistant and vancomycin-resistant Staphylococcus aureus strains. We report a unique, dose-dependent, antibacterial mechanism of action of ticagrelor, which alters the properties and integrity of the bacterial cytoplasmic membrane. Ticagrelor retains activity against multidrug-resistant staphylococci, including isolates carrying the most common in vivo selected daptomycin resistance mutations and vancomycin-intermediate Staphylococcus aureus. Our data support the use of ticagrelor as adjunct therapy against multidrug-resistant strains. Because of the presence of multiple non-protein targets of this drug within the bacterial membrane, resistance development is expected to be slow. All these findings corroborate the accumulating observational clinical evidence for a beneficial anti-bacterial effect of ticagrelor in cardiovascular patients in need of such treatment.

The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.

We demonstrate low-excitation transport and separation of two-ion crystals consisting of one ^{9}Be^{+} and one ^{40}Ca^{+} ion, with a high mass ratio of 4.4. The full separation involves transport of the mixed-species chain, splitting each ion into separate potential wells, and then transport of each ion prior to detection. We find the high mass ratio makes the protocol sensitive to mode crossings between axial and radial modes, as well as to uncontrolled radial electric fields that induce mass-dependent twists of the ion chain, which initially gave excitations n[over ¯]≫10. By controlling these stages, we achieve excitation as low as n[over ¯]=1.40±0.08phonons for the calcium ion and n[over ¯]=1.44±0.09phonons for the beryllium ion. Separation and transport of mixed-species chains are key elements of the quantum charge-coupled device architecture and may also be applicable to quantum-logic-based spectroscopy of exotic species.

Este estudo objetivou analisar as características de governança do ecossistema de inovação (EI) catarinense, localizado no Sul do Brasil. Seu foco é o Pacto pela Inovação, programa criado para aprimorar a colaboração dentro do ecossistema e que requer uma governança adequada. A coleta de dados foi conduzida por meio de entrevistas semiestruturadas, levantamento documental e questionário, aplicados a 41 organizações envolvidas nas 240 ações do programa. Os dados foram examinados por meio de triangulação e análise temática. Os resultados mostraram que a governança do ecossistema contempla diversos atores cujas relações são orientadas por mecanismos de coordenação. Apesar de haver liderança central, a abordagem de governança incentiva o protagonismo dos atores de forma descentralizada e com baixa formalidade. Contudo, a sustentabilidade do programa exige uma maior capacidade para mobilizar novos orquestradores. O estudo enfatiza a necessidade de evidências empíricas nos países em desenvolvimento, oferecendo perspectivas para gestores e decisores políticos empenhados em melhorar a capacidade colaborativa em EIs.

Abstract Consumer demand for natural, chemical-free products has grown. Food industry residues, like coffee pulp, rich in caffeine, chlorogenic acid and phenolic compounds, offer potential for pharmaceutical and cosmetic applications due to their antioxidant, anti-inflammatory, and antibacterial properties. Therefore, the objective of this work was to develop a phytocosmetic only with natural products containing coffee pulp extract as active pharmaceutical ingredient with antioxidant, antimicrobial and healing activity. Eight samples from Coffea arabica and Coffea canephora Pierre were analyzed for caffeine, chlorogenic acid, phenolic compounds, tannins, flavonoids, cytotoxicity, antibacterial activity, and healing potential. The Robusta IAC—extract had the greatest prominence with 192.92 μg/mL of chlorogenic acid, 58.98 ± 2.88 mg GAE/g sample in the FRAP test, 79.53 ± 5.61 mg GAE/g sample in the test of total phenolics, was not cytotoxic, and MIC 3 mg/mL against Staphylococcus aureus. This extract was incorporated into a stable formulation and preferred by 88% of volunteers. At last, a scratch assay exhibited the formulation promoted cell migration after 24 h, therefore, increased scratch retraction. In this way, it was possible to develop a phytocosmetic with the coffee pulp that showed desirable antioxidant, antimicrobial and healing properties.

The prominence of sketching and architectural observation has been displaced by the increasing use of CAD tools among architecture students. However, the thesis that these tools can be effectively used together is defended. The research employs a mixed-method design with two sequential phases. Firstly, the prevalence of CAD representations and the use of sketches in two-thirds of the projects are recognized for a sample of 102 thesis projects from the School of Architecture of Catholic University of the North-Chile. In the second phase, through a case study, the symbiosis of sketches with CAD, particularly in their prescriptive and speculative functions, is demonstrated. The article contributes to the discussion on the integration of analog and digital approaches in architectural education and prompts reflection on the continued relevance of sketches as an identity hallmark in the aforementioned school.

Abstract Leafcutter ants are among the most important agricultural and forest pests in the Neotropical region, given that they use plant matter as substrate for the growth of their mutualist fungus Leucoagaricus gongylophorus. Plant-based insecticides and fungicides have shown potential for controlling these ants. The present study assessed the hydroalcoholic extract activity of four fern fronds (dry and rainy periods) on the mutualist fungus of leafcutter ants. Fungal mycelium suspensions were seeded on the surface of tubes containing fern extracts at a concentration of 5 mg/mL and 100 μg/mL. The chemical profile of the extracts was analyzed by thin layer chromatography (TLC). Extracts (dry period) at a concentration of 5 mg/mL inhibited the growth of the fungus: Macrothelypteris torresiana and Dicksonia sellowiana (less than 20%), Niphidium crassifolium (approximately 40%), Parapolystichum effusum extract (100%). None of the extracts (dry and rainy periods) inhibited fungal growth at a concentration of 100 μg/mL. The chemical profile analysis of the extracts indicated the presence of beta-sitosterol, friedelinol, rutin, and kaempferol. The crude extracts of P. effusum and N. crassifolium were the most promising in future formulations of antifungal products. Thus, ferns are potential plants in the search for environmentally-friendly substances for sustainable agriculture.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Abstract Global surges in industrialization and human development have resulted in environmental contamination. Streambed sediment contamination threatens ecological and human health due to groundwater leaching and downstream contaminant mobilization. This is especially true in the wider Caribbean region, where streambed sediment contamination is understudied. In the current study, we assessed human impact on intermittent streams by measuring heavy metals and volatile organic compounds (VOCs) in streambed sediment on St. Croix in the United States Virgin Islands (USVI), where intermittent streams receive limited conservation and research attention. In contrast to our hypothesis that streambed sediment pollutant concentrations would be higher in developed, compared to undeveloped areas, contaminant concentrations did not vary significantly according to land cover. Elevated lead, mercury, and zinc concentrations were correlated with commercial building density, suggesting an unnatural origin of these elements in streambed sediment. At some sites, levels of arsenic, cadmium, chromium, nickel, lead, thallium, or zinc exceeded regulatory limits. The most prevalent VOCs at both developed and undeveloped sites were benzene and toluene. Sub-groups of heavy metals identified by principal component analysis indicated potential pollution sources, including fuel combustion (chromium, nickel, arsenic, selenium), vehicle exhaust, oil refining, and gasoline leaks (2-butanone and xylenes), and plastics (acetone and styrene). Our results suggest USVI intermittent streams require further research attention and intervention strategies for pollution reduction.

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety. Despite its potential benefits, the behavioral effects of NIA have not been thoroughly investigated. This study aimed to examine NIA’s potential as an anti-anxiety and anti-stress agent. After administering either vehicle or NIA in their drinking water to mice for 14 days, we conducted behavioral analyses using the Marble Burying Test and the Elevated Plus Maze test. NIA-treated mice spend more time in the open arms and bury fewer marbles. Moreover, a stability study confirmed the linear relationship between NIA concentration and its response across concentrations encompassing the NIA mother solution and the NIA solutions administered to mice. Also, a preliminary synaptic toxicity analysis showed no direct damage to cortical nerve endings. Here, we show that NIA can modulate anxiety-related behaviors without significantly impacting exploratory activity or adverse effects. Our work describes new findings that contribute to the research on safer and more tolerable anxiety management options.

Diffuse hemispheric glioma (DHG), H3 G34 mutant was included in the 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System recently published. Given the recent inclusion in the current classification and its rarity in adult patients, there are scarce data on clinical-radiological characteristics, survival, and outcome. The authors report the case of a 35-year-old female with DHG, H3 G34-mutant characteristics and outcomes with an unusual presentation, recurrence, and prolonged survival. In conclusion, our case report demonstrates relevant details that should be observed in patients with suspicion or confirmation of the diagnosis of DHG, H3 G34 mutant, not only in the initial presentation but also in the evolution to ensure more personalized treatment.

Abstract Background Clinical evidence is commonly obtained through individual trials that are time-, cost- and resource-consuming, and which often leave unanswered clinically relevant questions. Umbrella studies have been developed to address the need for more efficient and flexible trial structures, predominantly for cancer treatments. The umbrella concept foresees data collection within a unifying trial structure, to which one or more substudies may be added at any time to address product- or therapy-specific questions. To our knowledge, the umbrella concept has not yet been used in the medical device area, but it may offer similar advantages as in other settings, particularly in areas where multiple therapies are available within one large treatment area. Methods The MANTRA study (NCT05002543) is a prospective, global, post-marketing clinical follow-up study. The aim is to collect safety and device performance data covering the Corcym cardiac surgery portfolio for the treatment of aortic, mitral, and tricuspid valve diseases. The study uses a master protocol that outlines the main common parameters, and the specific questions are addressed in three substudies. The primary endpoints are device success at 30 days. Secondary endpoints include safety- and device performance-related data at 30 days, 1 year, and then annually through to 10 years. All endpoints are defined according to the more recent guidelines for heart valve procedures. Additionally, procedure and hospitalization information are collected, including Enhanced Recovery after Surgery in sites using such protocols, and patient outcome measures such as New York Heart Association classification and quality-of-life questionnaires. Results The study started in June 2021. Enrollment in all three substudies is ongoing. Conclusions The MANTRA study will provide contemporary information on the long-term outcomes of medical devices for the treatment of aortic, mitral, and tricuspid heart valve diseases in routine clinical practice. The umbrella approach adopted in the study has the potential of longitudinally assessing long-term efficacy of the devices and the flexibility to investigate new research questions as they arise.

Obiettivo La frequenza di segnalazione di atti violenti in ambito sanitario rappresenta il principale parametro per la Valutazione del Rischio (VdR) di subire aggressioni fisiche e/o verbali a danno degli operatori sanitari. Questo studio ha voluto indagare il fenomeno delle aggressioni in sanità, identificando una metodologia di valutazione multidimensionale per stimare e classificare il rischio anche in assenza di segnalazioni spontanee, operando quindi in fase di prevenzione. Materiali e metodi Inizialmente è stata condotta una revisione della letteratura già esistente per identificare i Fattori di Rischio (FdR) e le Misure di Prevenzione e Protezione (MPP); successivamente sono stati analizzati tali dati che hanno portato all’elaborazione di un algoritmo. Quest’ultimo è stato poi somministrato durante le VdR ad un totale di 32 unità operative appartenenti all’Azienda ULSS 4 "Veneto Orientale". Risultati l’attuazione di MPP ha abbassato il rischio espositivo iniziale in 22 delle 32 sedi valutate (68,7%). Le strutture a maggior rischio risultano essere quelle che applicano minori MPP in presenza di elevati FdR. Pronto Soccorso (PS), Servizio per le Dipendenze (SerD) e reparti di Medicina, considerati a maggior rischio dalla letteratura [5] [6] [15] [16], sono invece le unità operative che meglio conoscono il fenomeno e adottano di conseguenza maggiori MPP per contenerlo. La dimensione “paziente” è quella che pesa di più sulla determinazione dell’indice di rischio IR (35%). Discussione L’utilizzo di un algoritmo che mette in relazione FdR e MPP permette di identificare la composizione del rischio aggressioni in termini quantitativi e qualitativi. In questo modo la VdR risulta più completa, in quanto le sedi non sono valutate solamente attraverso i FdR [13] [14], ma anche pesando le MPP attuate per fronteggiare il fenomeno. Questo costituisce una novità nel campo della prevenzione. Conclusioni L'approccio utilizzato ha permesso di affermare che il rischio di aggressioni è multidimensionale ed è generato dalla complessa interazione di più fattori raggruppati nelle diverse dimensioni. Conoscere il rischio aiuta a prevenirlo e l’attuazione di idonee MPP, pur in presenza di elevati FdR, ne abbassa le potenzialità di danno.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Abstract Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8–12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: β-CD/citric acid and 2-hydroxypropyl-β-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa, revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants.

IntroductionAlthough staging of the extent of aortic stenosis (AS)-related cardiac damages is usually performed via echocardiography, this technique has considerable limitations in assessing pulmonary artery and right chamber pressures. The present hypothesis-generating study sought to explore the efficacy of a staging system of cardiac damage based on echocardiographic and invasive [right heart catheterization (RHC)] hemodynamic parameters in patients undergoing transcatheter aortic valve implantation (TAVI).MethodsWe studied 90 symptomatic patients with severe AS in whom echocardiographic and invasive evaluation by RHC was obtained prior to TAVI. Cardiac damage stages were defined as follows: no cardiac damage (stage 0), left ventricular (LV) damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), and right ventricular (RV) dysfunction or low-flow state (stage 4). With the integrative approach using RHC, pulmonary hypertension (PH) was defined as an mPAP ≥25 mmHg and the low-flow state corresponded to a cardiac index of 10 mmHg.ResultsDuring follow-up (median: 2.9 years), 43 patients (47.8%) died. The integrative cardiac damage staging was associated with a significant increase in all-cause and cardiovascular mortality per each increase of cardiac damage stage, whereas the outcome was similar according to the echocardiographic staging.ConclusionsA staging system of cardiac lesion based on echocardiographic and invasive hemodynamic parameters in patients with severe AS undergoing TAVI predicts mortality. Patients with pre-existing PH, ≥ moderate tricuspid regurgitation and/or RV dysfunction, and a low-flow state had a markedly increased risk of death. Further larger studies are needed to validate our findings.

A case study is used to achieve two research objectives: To understand students' attitudes, behavior toward, and satisfaction with videobooks vs. traditional textbooks; and to identify factors that drive student satisfaction and positive attitudes toward videobooks. Analysis of student experiences across multiple sections of an introductory marketing course found students have more positive attitudes toward, and higher satisfaction with, a videobook vs. a textbook. Further, students found the videobook to be easier to use and understand, and more engaging than a traditional textbook, making it overall more effective for learning. Finally, the videobook format facilitated the switch to virtual learning as its content delivery method more closely resembles in-class lectures.

Prima di attraversare una lunga fase di insuccesso letterario e di mercato, sancito dalla condanna che subisce nel clima di rigido aristotelismo cinquecentesco, il Bellum Civile di Lucano gode di una certa fortuna nel panorama librario italiano del primo Rinascimento. A comprovarlo è la pubblicazione di tre edizioni illustrate del poema, in due casi (Bologna 1493-95 e Milano 1525) con legni di riuso, nell’altro (Venezia 1511) con un set xilografico appositamente realizzato. L’articolo prende in esame queste stampe, cercando di identificare le scene raffigurate e il rapporto che intrattengono con i versi del poeta latino. Al tempo stesso, sono ricostruiti i legami tra le xilografie lucanee e alcune vignette impiegate in edizioni coeve (in particolare di Plutarco, Cesare, Virgilio e Ariosto), con l’obiettivo principale di mettere in luce le molteplici funzioni che gli editori assegnano all’apparato illustrativo. Lucan’s Bellum Civile enjoyed a certain degree of success in the Italian editorial context in the early Renaissance period, before undergoing a long period of misfortune determined by 16th century Aristotelian criticism. This success is proven by the publication of three different illustrated editions of the text; two of them (Bologna 1493-95 and Milan 1525) were realised reusing previous wood engravings, whereas new xylographs were specifically designed for the other one (Venice 1511). This article analyses the aforesaid editions, trying to identify the scenes depicted in the engravings and their interaction with the Latin text. Moreover, it focuses on the connection between Lucan’s xylographs and other contemporary illustrated editions of Plutarch, Caesar, Virgil and Ariosto, therefore shedding light on the various functions attributed to the iconographic apparatus by Renaissance editors.