Controlled Release of H2S from Biomimetic Silk Fibroin-PLGA Multilayer Electrospun Scaffolds.

The possibility of incorporating H2S slow-release donors inside biomimetic scaffolds can pave the way to new approaches in the field of tissue regeneration and anti-inflammatory treatment. In the present work, GYY4137, an easy-to-handle commercially available Lawesson's reagent derivative, has been successfully incorporated inside biomimetic silk fibroin-based electrospun scaffolds. Due to the instability of GYY4137 in the solvent needed to prepare silk fibroin solutions (formic acid), the electrospinning of the donor together with the silk fibroin turned out to be impossible. Therefore, a multilayer structure was realized, consisting of a PLGA mat containing GYY4137 sandwiched between two silk fibroin nanofibrous layers. Before their use in the multilayer scaffold, the silk fibroin mats were treated in ethanol to induce crystalline phase formation, which conferred water-resistance and biomimetic properties. The morphological, thermal, and chemical properties of the obtained scaffolds were thoroughly characterized by SEM, TGA, DSC, FTIR, and WAXD. Multilayer devices showing two different concentrations of the H2S donor, i.e., 2 and 5% w/w with respect to the weight of PLGA, were analyzed to study their H2S release and biological properties, and the results were compared with those of the sample not containing GYY4137. The H2S release analysis was carried out according to an "ad-hoc" designed procedure based on a validated high-performance liquid chromatography method. The proposed analytical approach demonstrated the slow-release kinetics of H2S from the multilayer scaffolds and its tunability by acting on the donor's concentration inside the PLGA nanofibers. Finally, the devices were tested in biological assays using bone marrow-derived mesenchymal stromal cells showing the capacity to support cell spreading throughout the scaffold and prevent cytotoxicity effects in serum starvation conditions. The resulting devices can be exploited for applications in the tissue engineering field since they combine the advantages of controlled H2S release kinetics and the biomimetic properties of silk fibroin nanofibers.

Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids.

Obesity (Ob), which has dramatically increased in the last decade, is one of the main risk factors that contribute to the incidence and progression of osteoarthritis (OA). Targeting the characteristics of obesity-associated osteoarthritis (ObOA) may offer new chances for precision medicine strategies in this patient cohort. First, this review outlines how the medical perspective of ObOA has shifted from a focus on biomechanics to the significant contribution of inflammation, mainly mediated by changes in the adipose tissue metabolism through the release of adipokines and the modification of fatty acid (FA) compositions in joint tissues. Preclinical and clinical studies on n-3 polyunsaturated FAs (PUFAs) are critically reviewed to outline the strengths and weaknesses of n-3 PUFAs' role in alleviating inflammatory, catabolic and painful processes. Emphasis is placed on potential preventive and therapeutic nutritional strategies based on n-3 PUFAs, with a focus on ObOA patients who could specifically benefit from reformulating the dietary composition of FAs towards a protective phenotype. Finally, tissue engineering approaches that involve the delivery of n-3 PUFAs directly into the joint are explored to address the perspectives and current limitations, such as safety and stability issues, for implementing preventive and therapeutic strategies based on dietary compounds in ObOA patients.

Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights.

Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain is still very challenging. In this regard, there is a growing body of evidence for the role of several bioactive dietary molecules (BDMs) in targeting inflammation and pain, with promising clinical results. BDMs may be valuable non-pharmaceutical solutions to treat and prevent the evolution of early OA to more severe phenotypes, overcoming the side effects of anti-inflammatory drugs. Among BDMs, polyphenols (PPs) are widely studied due to their abundance in several plants, together with their benefits in halting inflammation and pain. Despite their biological relevance, there are still many questionable aspects (biosafety, bioavailability, etc.) that hinder their clinical application. This review highlights the mechanisms of action and biological targets modulated by PPs, summarizes the data on their anti-inflammatory and anti-nociceptive effects in different preclinical in vitro and in vivo models of OA and underlines the gaps in the knowledge. Furthermore, this work reports the preliminary promising results of clinical studies on OA patients treated with PPs and discusses new perspectives to accelerate the translation of PPs treatment into the clinics.

The art gallery maze: a novel tool to assess human navigational abilities.

Humans differ widely in their ability to navigate effectively through the environment and in spatial memory skills. Navigation in the environment requires the analysis of many spatial cues, the construction of internal representations, and the use of various strategies. We present a novel tool to assess individual differences in human navigation, consisting of a virtual radial-arm maze presented as an art gallery to explore whether different sets of instructions (intentional or incidental) affect subjects' navigation performance. We furthermore tested the effect of the instructions on exploration strategies during both place learning and recall. We evaluated way-finding ability in 42 subjects, and individual differences in navigation were assessed through the analysis of navigational paths, which permitted the isolation and definition of a few strategies adopted by the incidental and intentional instructions groups. Our results showed that the intentional instruction group performed better than the other group: these subjects correctly paired each central statue and the two paintings in the adjacent arms, and they made less working and reference memory errors. Our analysis of path lengths showed that the intentional instruction group spent more time in the maze (thus being slower), specifically in the central hall, and covered more distance; the time spent in the main hall was, therefore, indicative of the quality of the following performance. Studying how environmental representations and the relative navigational strategies vary among "intentional" and "incidental" groups provides a new window into the acknowledgment of possible strategies to help subjects construct more efficient approaches in human navigation.

Learning from Monocyte-Macrophage Fusion and Multinucleation: Potential Therapeutic Targets for Osteoporosis and Rheumatoid Arthritis.

Excessive bone resorption by osteoclasts (OCs) covers an essential role in developing bone diseases, such as osteoporosis (OP) and rheumatoid arthritis (RA). Monocytes or macrophages fusion and multinucleation (M-FM) are key processes for generating multinucleated mature cells with essential roles in bone remodelling. Depending on the phenotypic heterogeneity of monocyte/macrophage precursors and the extracellular milieu, two distinct morphological and functional cell types can arise mature OCs and giant cells (GCs). Despite their biological relevance in several physiological and pathological responses, many gaps exist in our understanding of their formation and role in bone, including the molecular determinants of cell fusion and multinucleation. Here, we outline fusogenic molecules during M-FM involved in OCs and GCs formation in healthy conditions and during OP and RA. Moreover, we discuss the impact of the inflammatory milieu on modulating macrophages phenotype and their differentiation towards mature cells. Methodological approach envisaged searches on Scopus, Web of Science Core Collection, and EMBASE databases to select relevant studies on M-FM, osteoclastogenesis, inflammation, OP, and RA. This review intends to give a state-of-the-art description of mechanisms beyond osteoclastogenesis and M-FM, with a focus on OP and RA, and to highlight potential biological therapeutic targets to prevent extreme bone loss.

Hydrogen Sulfide in Bone Tissue Regeneration and Repair: State of the Art and New Perspectives.

The importance of hydrogen sulfide (H2S) in the regulation of multiple physiological functions has been clearly recognized in the over 20 years since it was first identified as a novel gasotransmitter. In bone tissue H2S exerts a cytoprotective effect and promotes bone formation. Just recently, the scientific community has begun to appreciate its role as a therapeutic agent in bone pathologies. Pharmacological administration of H2S achieved encouraging results in preclinical studies in the treatment of systemic bone diseases, such as osteoporosis; however, a local delivery of H2S at sites of bone damage may provide additional opportunities of treatment. Here, we highlight how H2S stimulates multiple signaling pathways involved in various stages of the processes of bone repair. Moreover, we discuss how material science and chemistry have recently developed biomaterials and H2S-donors with improved features, laying the ground for the development of H2S-releasing devices for bone regenerative medicine. This review is intended to give a state-of-the-art description of the pro-regenerative properties of H2S, with a focus on bone tissue, and to discuss the potential of H2S-releasing scaffolds as a support for bone repair.

A comparison of contact force and remote magnetic navigation on lesion formation for the ablation of atrial fibrillation.

RATIONALE: Pulmonary vein isolation (PVI) is the method of choice for the treatment of drug-resistant atrial fibrillation (AF). However, arrhythmia recurrences are frequent due to suboptimal lesions formation and pulmonary vein reconnection. Contact force (CF)- and remote magnetic navigation (RMN)-guided catheters are both capable of improving contact and energy transfer to the tissue, possibly improving PVI outcome. OBJECTIVE: The objective of our study was to compare CF- and RMN-guided PVI in patients with paroxysmal AF in terms of surrogate parameters of the dimension and quality of the lesions. METHODS AND RESULTS: Between March 2014 and March 2016, 44 patients affected by paroxysmal AF underwent a circumferential PVI procedure, 22 with a CF catheter and 22 with a RMN catheter. Signals were recorded before and after 30 seconds of radiofrequency point-by-point delivery. For each location, signal energy attenuation and impedance drop were evaluated as lesion dimension surrogates and signal fragmentation and shrinkage were estimated as lesion quality surrogates. Statistical analysis shows that CF catheter achieves higher attenuation and impedance drop than RMN-guided catheter, which instead performs better in terms of shrinkage and fragmentation. There were no differences in terms of PVI rate and sinus rhythm maintenance 1 year after the procedure (77.2% in both groups). CONCLUSIONS: CF-guided catheters produce lesions that are larger but less homogeneous than those produced by RMN-guided catheters in terms of surrogate parameters. These two features could possibly offset each other, resulting in identical acute and long-term outcomes.

Distinctive expression pattern of cystathionine-ß-synthase and cystathionine-γ-lyase identifies mesenchymal stromal cells transition to mineralizing osteoblasts.

Mesenchymal stromal cells (MSCs) are key players in the repair or regeneration of the damaged bone tissue. However, heterogeneity exists between MSCs derived from different donors in their bone formation ability both in vitro and in vivo. The identification of markers defining MSCs with different functional phenotypes is fundamental to maximize their clinical potential. In our previous in vivo study, impaired expression in MSCs of cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE), the two key enzymes in the catabolic pathway of homocysteine, was associated to decreased bone formation and to the onset of osteoporosis in mice. Here, we investigated whether osteogenic differentiation of human MSCs (hMSCs) modulates the expression of CBS and CSE. The expression of CBS and CSE was also assessed during chondrogenesis to confirm the specificity of their expression during osteogenesis. hMSCs displayed a heterogeneous mineralizing capacity between donors (70% of the samples mineralized, while 30% did not mineralize). Inducible expression of CBS and CSE was found to be associated with a mineralizing phenotype in hMSCs. In particular, up-regulation of CSE was restricted to hMSCs undergoing mineralization. During chondrogenesis, CBS was significantly up-regulated while CSE expression was not affected. Ex-vivo findings confirmed that mature h-osteoblasts (hOBs) show consistently higher expression of CBS and CSE than hMSCs. Our data provide the first evidence that the expression of CBS and CSE in hMSCs closely correlates with the transition of hMSCs toward the osteoblastic phenotype and that CSE may constitute a novel marker of osteogenic differentiation.

Atrial Conduction Velocity Correlates with Frequency Content of Bipolar Signal.

BACKGROUND: Anisotropy in conduction velocity (CV) is a key substrate abnormality influencing atrial arrhythmias. In skeletal muscle fibers, CV and frequency content of the surface electromyogram signal are directly related. We hypothesized that in human atria the frequency content of the bipolar signal, recorded on the endocardial surface, is directly related to the local CV. METHODS: In 15 patients submitted to ablation of supraventricular arrhythmias, incremental pacing was performed through an octapolar catheter inserted into the coronary sinus (CS), alternatively from both extremities in two different sequences: CS bipole 1-2 as the pacing site and CS bipole 7-8 as the detection site in the first, and vice versa in the second. The pacing cycle length (PCL) was stepwise decreased from 600 ms to 500 ms, 400 ms, 300 ms, until 250 ms. Estimation of the CV was performed as the ratio between the distance traveled by the propagating pulse and the propagation time. The frequency distribution of the signal energy was estimated using the fast Fourier transform, and the characteristic frequency (CF) was estimated as the barycenter of the frequency spectrum. RESULTS: A total of 2,496 bipolar signals were analyzed; CV and CF were estimated and compared. The single patient and group data analysis showed a significant direct correlation between CV and CF of the local bipolar signal. CONCLUSIONS: Comparing the degree of spectral compression among signals registered in different points of the endocardial cardiac surface in response to decreasing PCL enables to map local differences in CV, a useful arrhythmogenic substrate index.

Posidonia oceanica (L.) based compost as substrate for potted basil production.

BACKGROUND: Peat is the main component of growing media but is also a non-renewable resource; therefore European policy strongly encourages the use of peat alternatives such as compost. Posidonia is a Mediterranean seagrass that produces very conspicuous onshore deposits that can be composted. In this study, a commercial green compost and a Posidonia residue-based compost were tested in order to assess their potential use as substitutes or complements to peat. RESULTS: All macro and micro-element concentrations of the substrates were positively and significantly related to the percentage of composts in the growing media. Plant grown on peat showed higher content of P, Ca, K, Na, Cu, Mn, Zn and Fe, and a slightly higher biomass production in comparison to compost-based growing media. In contrast, plants grown on compost-based substrates showed lower uptake of Cd and Cr than peat. CONCLUSION: The results indicate that both composts can be used as a complement to the peat for substrate preparation, especially at a rate of 30%. The Posidonia-based compost showed better productive results in comparison to the green one. Basil grown on the two compost-based media showed reduced absorption level of potentially toxic metals in comparison to peat.

Sodium hydrosulfide inhibits the differentiation of osteoclast progenitor cells via NRF2-dependent mechanism.

Hydrogen sulfide (H2S), which recently emerged as a potent regulator of tissues and organs, is broadly produced in mammalian cells but whether it can regulate bone cell function is still elusive. The main objective of this study was to establish the role of H2S in the regulation of human osteoclast differentiation and function. Sodium hydrosulfide (NaHS), a common H2S-donor, was administered in vitro to CD11b+ human monocytes, the pool of circulating osteoclasts precursors which are critically involved in osteoclast development and function in bone. NaHS dose-dependently decreased human osteoclast differentiation at concentrations which did not induce toxicity. The inhibition of human osteoclast differentiation was associated with a down-regulation in RANKL-dependent intracellular ROS levels in human pre-osteoclasts cells. Furthermore, NaHS up-regulated NRF2 protein expression, its nuclear translocation, and the transcription of the two key downstream antioxidant genes Peroxiredoxin-1 and NAD(P)H dehydrogenase quinone 1, suggesting that NRF2 activation may inhibit human osteoclast differentiation by activating a sustained antioxidant response in osteoclast progenitors; furthermore, NRF2 activators Sulforaphane and Tert-butylhydroquinone inhibited in vitro human osteoclast differentiation. Moreover, silencing NRF2 in human pre-osteoclasts totally abolished NaHS-mediated inhibition of osteoclastogenesis, suggesting that NRF2 is essential to the inhibitory function of NaHS in osteoclast development. Finally, we found that NaHS also downregulated the RANKL/OPG mRNA ratio in human mesenchymal stem cells, the key osteoclast-supporting cells. Our results suggest that NaHS shows a potential therapeutical role in erosive diseases of bone by regulating both direct and indirect mechanisms controlling the differentiation of circulating osteoclasts precursors.

Surfactant-assisted photo-crosslinked silk fibroin sponges: A versatile platform for the design of bone scaffolds.

Critical size bone defects cannot heal without aid and current clinical approaches exhibit some limitations, underling the need for novel solutions. Silk fibroin, derived from silkworms, is widely utilized in tissue engineering and regenerative medicine due to its remarkable properties, making it a promising candidate for bone tissue regeneration in vitro and in vivo. However, the clinical translation of silk-based materials requires refinements in 3D architecture, stability, and biomechanical properties. In earlier research, improved mechanical resistance and stability of chemically crosslinked methacrylate silk fibroin (Sil-Ma) sponges over physically crosslinked counterparts were highlighted. Furthermore, the influence of photo-initiator and surfactant concentrations on silk properties was investigated. However, the characterization of sponges with Sil-Ma solution concentrations above 10 % (w/V) was hindered by production optimization challenges, with only cell viability assessed. This study focuses on the evaluation of methacrylate sponges' suitability as temporal bone tissue regeneration scaffolds. Sil-Ma sponge fabrication at a fixed concentration of 20 % (w/V) was optimized and the impact of photo-initiator (LAP) concentrations and surfactant (Tween 80) presence/absence was studied. Their effects on pore formation, silk secondary structure, mechanical properties, and osteogenic differentiation of hBM-MSCs were investigated. We demonstrated that, by tuning silk sponges' composition, the optimal combination boosted osteogenic gene expression, offering a strategy to tailor biomechanical properties for effective bone regeneration. Utilizing Design of Experiment (DoE), correlations between sponge composition, porosity, and mechanical properties are established, guiding tailored material outcomes. Additionally, correlation matrices elucidate the microstructure's influence on gene expressions, providing insights for personalized approaches in bone tissue regeneration.

On the dynamics of gain and loss: Electrophysiological evidence from associative learning.

Associated relevance affects the sensory encoding of low-level visual features of symbolic stimuli. It is unclear, however, which dimension of low-level visual features benefits from prioritized processing, and how these effects develop throughout the course of relevance acquisition. Moreover, previous evidence is inconclusive regarding the preservation of processing advantage once the association is no longer relevant, as well as its generalization to perceptually similar but novel stimuli. The present study addresses these questions by employing an associative learning paradigm. In two experiments (N = 24 each, between-subject design), different dimensions of low-level visual features of symbolic stimuli were associated with monetary gain, loss, or zero outcome. In a consecutive old/new decision task, associated stimuli were presented together with perceptually similar but novel stimuli. Event-related brain potentials (P1, EPN, LPC) were measured throughout both sessions. Early sensory encoding (P1) was boosted by loss association and appeared to be sensitive to the dimension of the associated low-level visual features. Gain association influenced post-perceptual processing stages (LPC), arising over the course of the learning phase, and are preserved even when the associated outcome was no longer relevant. Gain association also resulted in EPN modulations similar to the effects observed in the case of emotional words. None of the observed effects generalized to perceptually similar stimuli. These results show that acquired relevance can influence the sensory processing of specific dimensions of low-level visual features. Moreover, this study extends previous evidence of a dissociation of early and late neural effects of associated motivational relevance.

Facing the Shadow Pandemic: Correlation and Trend Analyses of Violence Reports from Women to the Italian National Anti-Violence Number during 2021.

OBJECTIVES: To help to tackle gender-based violence against women in the aftermath of COVID-19 or other potential crisis situations, as recommended by the European Institute for Gender Equality, the present study aims to investigate the relationship between calls to the National Anti-violence Number (NAN) and the socio-sanitary pandemic factors during 2021, a period in which the scenario changed due to containment measures that gradually allowed women to emerge from the condition of isolation. In addition, the present work aims to identify significant changes in the number of calls to NAN during the progression of the pandemic in 2021. METHODS: Using Italian Civil Protection Department data on the socio-sanitary pandemic factors (defined by daily number of cases, swabs, deaths, hospitalizations, dismissions, intensive care unit hospitalizations, people isolated at home, and quarantine after 15 and 30 days) and NAN data. Correlation analyses, a joinpoint regression analysis, and Granger causality tests were performed. RESULTS: The number of calls correlated with the daily number of cases, swabs, deaths, hospitalizations, dismissions, intensive care unit hospitalizations, and quarantine after 15 and 30 days. The identified joinpoints showed significant changes in the number of daily anti-violence calls during the year. Furthermore, we found evidence of a significant causality between daily hospitalizations, daily home quarantined, daily dismissed patients, and calls to NAN. CONCLUSIONS: The results underline the influence of containment measures on the increased access to NAN, suggesting the need for a greater implementation of social and psychological support services in other potential crisis situations.

Magnetic resonance imaging based neurosurgical planning on hololens 2: A feasibility study in a paediatric hospital.

Objective: The goal of this work is to show how to implement a mixed reality application (app) for neurosurgery planning based on neuroimaging data, highlighting the strengths and weaknesses of its design. Methods: Our workflow explains how to handle neuroimaging data, including how to load morphological, functional and diffusion tensor imaging data into a mixed reality environment, thus creating a first guide of this kind. Brain magnetic resonance imaging data from a paediatric patient were acquired using a 3 T Siemens Magnetom Skyra scanner. Initially, this raw data underwent specific software pre-processing and were subsequently transformed to ensure seamless integration with the mixed reality app. After that, we created three-dimensional models of brain structures and the mixed reality environment using Unity™ engine together with Microsoft® HoloLens 2™ device. To get an evaluation of the app we submitted a questionnaire to four neurosurgeons. To collect data concerning the performance of a user session we used Unity Performance Profiler. Results: The use of the interactive features, such as rotating, scaling and moving models and browsing through menus, provided by the app had high scores in the questionnaire, and their use can still be improved as suggested by the performance data collected. The questionnaire's average scores were high, so the overall experiences of using our mixed reality app were positive. Conclusion: We have successfully created a valuable and easy-to-use neuroimaging data mixed reality app, laying the foundation for more future clinical uses, as more models and data derived from various biomedical images can be imported.

Extracellular calcium chronically induced human osteoblasts effects: specific modulation of osteocalcin and collagen type XV.

Fluctuation in extracellular calcium (Ca(2+)) concentration occurs during bone remodeling. Free ionized Ca(2+) plays a critical role in regulating osteoblast functions. We analyzed the effects of different concentrations of free ionized Ca(2+) (0.5, 1.3, and 2.6 mM) on human osteoblasts and we evaluated osteoblastic phenotype (marker expression and cell morphology) and functions (osteogenic differentiation, cell proliferation, and cell signaling). Our data show human osteoblasts that chronically stimulated with 0.5, 1.3, or 2.6 mM Ca(2+) significantly increase intracellular content of alkaline phosphatase, collagen type I, osteocalcin, and bone sialoprotein, whereas collagen type XV was down-modulated and RUNX2 expression was not affected. We also found a Ca(2+) concentration-dependent increase in osteogenic differentiation and cell proliferation, associated to an increase of signaling protein PLCß1 and p-ERK. Human osteoblast morphology was affected by Ca(2+) as seen by the presence of numerous nucleoli, cells in mitosis, cell junctions, and an increased number of vacuoles. In conclusion, our data show a clear phenotypical and functional effect of extracellular Ca(2+) on human osteoblasts and support the hypothesis of a direct role of this cation in the bone remodeling processes.

Dietary organosulfur compounds: Emerging players in the regulation of bone homeostasis by plant-derived molecules.

The progressive decline of bone mass and the deterioration of bone microarchitecture are hallmarks of the bone aging. The resulting increase in bone fragility is the leading cause of bone fractures, a major cause of disability. As the frontline pharmacological treatments for osteoporosis suffer from low patients' adherence and occasional side effects, the importance of diet regimens for the prevention of excessive bone fragility has been increasingly recognized. Indeed, certain diet components have been already associated to a reduced fracture risk. Organosulfur compounds are a broad class of molecules containing sulfur. Among them, several molecules of potential therapeutic interest are found in edible plants belonging to the Allium and Brassica botanical genera. Polysulfides derived from Alliaceae and isothiocyanates derived from Brassicaceae hold remarkable nutraceutical potential as anti-inflammatory, antioxidants, vasorelaxant and hypolipemic. Some of these effects are linked to the ability to release the gasotrasmitter hydrogen sulfide (H2S). Recent preclinical studies have investigated the effect of organosulfur compounds in bone wasting and metabolic bone diseases, revealing a strong potential to preserve skeletal health by exerting cytoprotection and stimulating the bone forming activity by osteoblasts and attenuating bone resorption by osteoclasts. This review is intended for revising evidence from preclinical and epidemiological studies on the skeletal effects of organosulfur molecules of dietary origin, with emphasis on the direct regulation of bone cells by plant-derived polysulfides, glucosinolates and isothiocyanates. Moreover, we highlight the potential molecular mechanisms underlying the biological role of these compounds and revise the importance of the so-called 'H2S-system' on the regulation of bone homeostasis.

How German and Italian Laypeople Reason about Distributive Shortages during COVID-19.

(1) Background: The COVID-19 pandemic provided a unique opportunity to investigate how moral reasoning is influenced by individuals' exposure to a crisis and by personal, societal and temporal proximity. We examined how Italians and Germans judged different behaviors that arose because of the pandemic, which affected health and societal matters. (2) Methods: Over the course of four months and three assessment periods, we used an observational online survey to assess participants' judgments regarding seven scenarios that addressed distributive shortages during the pandemic. (3) Results: Overall, there was no clear answering pattern across all scenarios. For a variation of triage and pandemic restrictions, most participants selected a mean value, which can be interpreted as deferring the choice. For the other scenarios, most participants used the extremes of the scale, thereby reflecting a clear opinion of the public regarding the moral issue. In addition, moral reasoning varied across the two countries, assessment periods, fear, and age. (4) Conclusions: By using scenarios that were taken from real-life experiences, the current study addresses criticism that moral research mostly relies on unrealistic scenarios that lack in external validity, plausibility, and proximity to everyday situations. In addition, it shows how lay people regard measures of public health and societal decision-making.

Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries.

Schistosomiasis is a neglected tropical disease that affects over 200 million people annually. As the antischistosomal drug pipeline is currently empty, repurposing of compound libraries has become a source for accelerating drug development, which demands the implementation of high-throughput and efficient screening strategies. Here, we present a parallelized impedance-based platform for continuous and automated viability evaluation of Schistosoma mansoni schistosomula in 128 microwells during 72 h to identify antischistosomal hits in vitro. By initially screening 57 repurposed compounds against larvae, five drugs are identified, which reduce parasite viability by more than 70%. The activity profiles of the selected drugs are then investigated via real-time dose-response monitoring, and four compounds reveal high potency and rapid action, which renders them suitable candidates for follow-up tests against adult parasites. The study shows that our device is a reliable tool for real-time drug screening analysis of libraries to identify new promising therapeutics against schistosomiasis.

Methacrylated Silk Fibroin Additive Manufacturing of Shape Memory Constructs with Possible Application in Bone Regeneration.

Methacrylated silk (Sil-MA) is a chemically modified silk fibroin specifically designed to be crosslinkable under UV light, which makes this material applicable in additive manufacturing techniques and allows the prototyping and development of patient-specific 2D or 3D constructs. In this study, we produced a thin grid structure based on crosslinked Sil-MA that can be withdrawn and ejected and that can recover its shape after rehydration. A complete chemical and physical characterization of Sil-MA was first conducted. Additionally, we tested Sil-MA biocompatibility according to the International Standard Organization protocols (ISO 10993) ensuring the possibility of using it in future trials. Sil-MA was also tested to verify its ability to support osteogenesis. Overall, Sil-MA was shown to be biocompatible and osteoconductive. Finally, two different additive manufacturing technologies, a Digital Light Processing (DLP) UV projector and a pneumatic extrusion technique, were used to develop a Sil-MA grid construct. A proof-of-concept of its shape-memory property was provided. Together, our data support the hypothesis that Sil-MA grid constructs can be injectable and applicable in bone regeneration applications.