Search

Osteoarthritis is characterized by enzymatic breakdown of the articular cartilage via the disruption of chondrocyte homeostasis, ultimately resulting in the destruction of the articular surface. Decades of research have highlighted the importance of inflammation in osteoarthritis progression, with inflammatory cytokines shifting resident chondrocytes into a pro-catabolic state. Inflammation can result in poor outcomes for cells implanted for cartilage regeneration. Therefore, a method to promote the growth of new cartilage and protect the implanted cells from the pro-inflammatory cytokines found in the joint space is required. In this study, we fabricate two gel types: polymer network hydrogels composed of chondroitin sulfate and hyaluronic acid, glycosaminoglycans (GAGs) known for their anti-inflammatory and prochondrogenic activity, and interpenetrating networks of GAGs and collagen I. Compared to a collagen-only hydrogel, which does not provide an anti-inflammatory stimulus, chondrocytes in GAG hydrogels result in reduced production of pro-inflammatory cytokines and enzymes as well as preservation of collagen II and aggrecan expression. Overall, GAG-based hydrogels have the potential to promote cartilage regeneration under pro-inflammatory conditions. Further, the data have implications for the use of GAGs to generally support tissue engineering in pro-inflammatory environments.

Continuous tertiary filtration with rotating polymeric discs were studied as post treatment of effluent urban wastewater in real plant (10,000 PE) and of landfill leachate or zootechnical wastes in laboratory scale. For the urban flow, different TSS and hydraulic loads were tested to determine the performances of the device. The particle size distribution, the microscope analysis and the filamentous count for the treated flows was executed to better understand the effect of the bulking sludge characteristics in terms of solids removals and of number of performed backwashing cycles. The average TSS removals were found equal to 89%±12% (11 micron) and the TSS effluent concentrations were always lower than 5 mg/l. Bimodality granulometric distribution and filamentous bacteria presence increase the performances of the filtration phase. The not applicability of this treatment for the tested industrial wastes was demonstrated in laboratory scale.

Iron pill inhalation represents a uncommon cause of syntomatic endobronchial foreign bodies. Unlike foreign body, the direct contact of iron tablet onto the bronchial mucosa results in severe bronchial damage in addition to obstruction and local irritation. Four patients with Iron Pill Inhalation Syndrome are described. All but one patient developed irreversible bronchial stenosis as late post inflammatory complication. Bronchoscopic features and clinical evolution are described in order to reduce the risk of severe side-effects in patients highly suspected for iron pill aspiration.

ABSTRACT Limiting the availability of transition metals at infection sites serves as a critical defense mechanism employed by the innate immune system to combat microbial infections. Pseudomonas aeruginosa exhibits a remarkable ability to thrive in zinc-deficient environments, facilitated by intricate cellular responses governed by numerous genes regulated by the zinc-responsive transcription factor Zur. Many of these genes have unknown functions, including those within the predicted PA2911-PA2914 and PA4063-PA4066 operons. A structural bioinformatics investigation revealed that PA2911-PA2914 comprises a TonB-dependent outer membrane receptor and inner membrane ABC-permeases responsible for importing metal-chelating molecules, whereas PA4063-PA4066 contains genes encoding a MacB transporter, likely involved in the export of large molecules. Molecular genetics and biochemical experiments, feeding assays, and intracellular metal content measurements support the hypothesis that PA2911-PA2914 and PA4063-PA4066 are engaged in the import and export of the pyochelin-cobalt complex, respectively. Notably, cobalt can reduce zinc demand and promote the growth of P. aeruginosa strains unable to import zinc, highlighting pyochelin-mediated cobalt import as a novel bacterial strategy to counteract zinc deficiency. These results unveil an unexpected role for pyochelin in zinc homeostasis and challenge the traditional view of this metallophore exclusively as an iron transporter.IMPORTANCEThe mechanisms underlying the remarkable ability of Pseudomonas aeruginosa to resist the zinc sequestration mechanisms implemented by the vertebrate innate immune system to control bacterial infections are still far from being fully understood. This study reveals that the Zur-regulated gene clusters PA2911-2914 and PA4063-PA4066 encode systems for the import and export of cobalt-bound pyochelin, respectively. This proves to be a useful strategy to counteract conditions of severe zinc deficiency since cobalt can replace zinc in many proteins. The discovery that pyochelin may contribute to cellular responses to zinc deficiency leads to a reevaluation of the paradigm that pyochelin is a siderophore involved exclusively in iron acquisition and suggests that this molecule has a broader role in modulating the homeostasis of multiple metals.

Lysosomes are crucial for degradation and recycling of damaged proteins and cellular components. Therapeutic strategies enhancing lysosomal function are a promising approach for aging and age-related neurodegenerative diseases. Here, we show that an FDA approved drug sodium polystyrene sulfonate (SPS), used to reduce high blood potassium in humans, enhances lysosomal function both in C. elegans and in human neuronal cells. Enhanced lysosomal function following SPS treatment is accompanied by the suppression of proteotoxicity caused by expression of the neurotoxic peptides Aβ and TAU. Additionally, treatment with SPS imparts health benefits as it significantly increases lifespan in C. elegans. Overall our work supports the potential use of SPS as a prospective geroprotective intervention.

The landfill is the most common final destination of the municipal solid wastes. Therefore, the landfill leachate is a serious environmental priority. The characteristics of the leachate are mainly related to the high ammonia concentrations, the low bioavailable carbon, the heavy metals and the inorganic salts. Consequently, the biological activated sludge treatment of landfill leachate is considered a low efficiency process in terms of nitrogen removal and of aeration transfer capacity and it is characterized by elevated stripping of ammonia. For these reasons, best operative practices have to be performed for the optimization of the removals and for the energy savings when, as in this case, the biological process is applied. First of all, the increment of the soluble free ammonia (up to NH3 of 13.9 mg/L) coupled with the dissolved oxygen limiting conditions (

The treatment or recovery of nutrients (N and P) from anaerobically digested supernatants is now a central topic, related both to the zootechnical wastewaters and the supernatants from the sludge lines of urban wastewater treatment plants (WWTP), applying codigestion of excess sludge and organic fraction of municipal solid waste (OFMSW). In both cases, the crystallization and precipitation of Struvite (Magnesium Ammonium Phosphate) is a hypothetical solution to reduce the high concentrations of ammonia nitrogen and to reuse the final product. This study shows the effects of the main variables of Struvite crystallization (pH, reaction time and dosage modality) applied in bench scale to anaerobic zootechnical and codigested urban supernatants. The matrices with initial concentrations of NH4-N from 1000 to 2000 mgL-1, were added to phosphoric acid (source of P) and magnesium oxide (source of Mg), pure and of industrial origin, to achieve the correct molar ratios. Adjustment of the pH at 8.5 was provided through NaOH dosage. The experimental tests, at increasing ratios (Mg:N:P) from 1:1:1 to 2:1:1, have been carried out at reaction times from 0 to 60 minutes and at two distinct dosage modalities. Indeed, the dosing tests were firstly provided by direct addition of the different reagents and next by indirect addition, with the prior dilution of the magnesium source in the phosphoric acid. The results defined as the different sequence of reagents addition modifies the percentage of struvite formation and, consequently, the ammonia decrease. Specifically, compared to the obtained efficiencies range between 50 % and 70 % with direct dosage, the tests with indirect dosage allow the recovery of nitrogen greater than 20 %, at the same molar ratios and reaction times. The time factor does not affect the precipitation more than 10 %, regardless of the dosage carried out. Further, the use of a thermodynamic model allowed to assess and justify the transformation of other ions in solution (K+ and Ca++) highlighting the formation of other secondary compounds (k-struvite,hydroxyapatite).

Abstract preview not available - see full-text PDF article.

Not available.

In this study, the effect of start of injection (SOI) timing is investigated on a single cylinder spark ignited (SI) internal combustion engine (ICE) fueled with hydrogen, using Computational Fluid Dynamics (CFD) simulations. Mixing fields and combustion behaviors at different relative air-fuel ratios (λ) and injection strategies are discussed. Direct injection (DI) cases with three different SOI timings for each λ are compared against port-fuel injection (PFI) cases modeled assuming perfectly premixed charge at the intake plenum. Results for the investigated cases show that PFI cases at λ = 2 and λ = 3 have very high combustion efficiency while at λ = 3.5 partial burn occurs (only 70% of the fuel is oxidized). In DI cases, combustion efficiency decreases compared to corresponding premixed situations, as expected, but significant improvements are obtained by advancing the SOI timing towards the end of the intake stroke. In addition, early SOI timings tend to reduce the duration of initial combustion stage, CA0-10, which correlates with ignition repeatability, therefore suggesting potential benefits on combustion stability under very lean conditions. The method and results of this work can be used as a guideline for developing efficient hydrogen injection strategies.

Hydrogels have been widely investigated in biomedical fields due to their similar physical and biochemical properties to the extracellular matrix (ECM). Collagen and hyaluronic acid (HA) are the main components of the ECM in many tissues. As a result, hydrogels prepared from collagen and HA hold inherent advantages in mimicking the structure and function of the native ECM. Numerous studies have focused on the development of collagen and HA hydrogels and their biomedical applications. In this extensive review, we provide a summary and analysis of the sources, features, and modifications of collagen and HA. Specifically, we highlight the fabrication, properties, and potential biomedical applications as well as promising commercialization of hydrogels based on these two natural polymers.

Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.

Should the appliances change to adapt to new conditions in the current scenario of a compromised environmental situation? The human needs to cook food, wash dishes and do laundry are the same, but society and our relationship with mother nature have changed radically. Although many contributions to the design for sustainability, the changes in the design sector and the market are not always visible. This paper is part of a research project on the design of appliances for the circular economy scenario and intends to understand Is there the need to re-design the current one, design new ones, or invent something else? How to decide? Are we considering all the aspects? The problem was tackled using a systemic design approach. The result is a framework that contains the data collected by the research steps, maps all the implications that the design of appliances in the circular economy scenario should consider in the process, and visualises the complexity of the topic.

Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS. Moreover, a number of anticancer treatments has been reported to possibly cause TTS as a form of cardiotoxicity, even though clearcut associations are lacking. The aim of this narrative review is to sum up contemporary knowledge on the association of cancer and TTS, addressing unmet needs and practical implications. The importance of a close collaboration between cardiologists and oncologists is herein highlighted, both to allow an adequate management of the acute TTS phase, and to actively and safely return to the oncologic management once the acute setting is resolved.

Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target.Methods: The FOOT experiment has been designed to measure the cross sections of the nuclear fragmentation of projectile and target with two different detectors: an electronic setup for the identification of Z ≥ 3 fragments and a nuclear emulsion spectrometer for Z ≤ 3 fragments. In this paper, we analyze the data taken by exposing four nuclear emulsion spectrometers, with C and C2H4 targets, to 200 MeV/n and 400 MeV/n oxygen beams at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany), and we report the charge identification of produced fragments based on the controlled fading induced on nuclear emulsion films.Results: The goal of identifying fragments as heavy as lithium has been achieved.Discussion: The results will contribute to a better understanding of the nuclear fragmentation process in charged particle therapy and have implications for refining treatment planning in the presence of deep-seated tumors.

Hydrogen fuel is gaining particular attention in internal combustion engines. In addition to zero-carbon emissions, major advantages relate to its combustion characteristics, which allow a significant increase in thermal efficiency under ultra-lean operation and with very low NOx levels. The ignition system is one of the main technology enablers, as it determines the capability to control ultra-lean operations, avoid backfire phenomena, and/or reduce the risks of abnormal combustions. The latter results from hydrogen’s low ignition energy and it is associated with factors like high-temperature residuals, hot spots, and irregular spark plug discharge. The ACIS gen 2-Barrier Discharge Igniter excels in accelerating the initial flame growth speed by the generation of non-equilibrium low-temperature plasma, a strong ignition promoter for the combined action of kinetic and thermal effects. Moreover, its volumetric discharge facilitates combustion initiation on a wide region, in contrast to the localized ignition of traditional spark systems. In this work we present for the first time, to the best of our knowledge, experimental results showing the performance of a hydrogen engine with a low-temperature plasma discharge. Tests were conducted on a single-cylinder research engine, achieving ultra-lean conditions with cycle-to-cycle variability results below 2.5%. The analysis indicates that the H2-BDI combined solution is capable of accelerating the evolution of the flame front compared to traditional spark plugs, leading to a significant reduction in the cycle-to-cycle variability. A meticulous adjustment of the BDI control parameters further enhances igniter performance and contributes to a deeper understanding of the innovative approach proposed in this study.

Currently, conventional spark–ignition engines face challenges in meeting the ever-growing demands of customers and increasingly stringent regulations regarding pollutant emissions. A combination of innovative strategies and carbon-neutral fuels is deemed necessary in order to further reduce fuel consumption and minimize engine emissions. The present work aims to assess the performance of combustion strategies using low-carbon-content fuel, such as methanol M100, ignited by a plasma-assisted igniter (PAI) under ultra-lean conditions. The experimental campaign is conducted on a single-cylinder research engine at 1000 rpm and low loads, moving up to the engine lean stable limits. The specific purpose of this work is to determine the benefits brought by the proposed strategy, referred to as M100–PAI, which compared market gasoline E5 ignited by the PAI system and conventional spark. The synergy between M100 (methanol) and Plasma-Assisted Ignition (PAI) in internal combustion engines yielded notable benefits. This combination significantly improved combustion stability if compared to the other combinations tested, by extending the lean stable limit to λ = 2.0, reducing cycle-to-cycle variability, and facilitating faster flame front acceleration, resulting in enhanced homogeneity. These enhancements, obtained with the combination M100–PAI, contributed to higher fuel efficiency, showing a 10% efficiency gain over the combination E5–gasoline spark ignition. The findings highlight the potential of innovative combustion strategies using low-carbon fuels and advanced ignition systems to meet stringent emissions regulations while improving engine performance.

Inguinoscrotal hernia is a common pediatric disease but a rare condition in the fetus. We present a case, from our institution, of fetal inguinoscrotal hernia with possible rapid development. In addition to our case, we present a literature update on fetal inguinoscrotal hernia in order to enhance the ability to recognize it from the other scrotal masses on ultrasound. Antenatal management, differential diagnosis and postnatal management are also discussed.

En el presente trabajo me interesa observar cómo ciertos ideogramas que configuran la obra de Alejandra Pizarnik (la viajera, la muerta, la olvidada, la niña, la insomne) y que, vueltos lugares comunes, contribuyeron a mitificar su figura autoral como poeta maldita, asociados a una dimensión espacio-temporal permitirían “mensurar” la forma y el tamaño del yo lírico y diarístico. En efecto, en su poesía y en sus diarios, el yo se autofigura pequeño, miniaturizado y, paradójicamente, resulta magnánimo, acaso porque el espacio exterior —a excepción del bosque y el jardín— es prácticamente nulo: como si algunas de las características que podemos suponer del paisaje (variedad, multiplicidad, extensión) hubieran sido fagocitadas por el yo que se despliega desorbitado y abismal, renuente a admitir un afuera. Esta hiper concentración egoica miniaturizada, además de dar a la obra total cierto tono asfixiante, habilita a conjeturar acerca del estricto régimen de pureza de su poesía y de la imposibilidad de escribir una novela, consignada, sin descanso, en sus diarios.

Machine learning based on neural networks facilitates data-driven techniques for handling large amounts of data, either obtained through experiments or simulations at multiple spatio-temporal scales, thereby finding the hidden patterns underlying these data and promoting efficient research methods. The main purpose of this paper is to extend the capabilities of a new solver called realFluidReactingNNFoam, under development at the University of Perugia, in OpenFOAM with a neural network algorithm for replacing complex real-fluid thermophysical property evaluations, using the approach of coupling OpenFOAM and Python-trained neural network models. Currently, neural network models are trained against data generated using the Peng–Robinson equation of state assuming a mixture’s frozen temperature. The OpenFOAM solver, where needed, calls the neural network models in each grid cell with appropriate inputs, and the returned results are used and stored in suitable OpenFOAM data structures. Such inference for thermophysical properties is achieved via the “Neural Network Inference in C made Easy (NNICE)” library, which proved to be very efficient and robust. The overall model is validated considering a liquid-rocket benchmark comprised of liquid-oxygen (LOX) and gaseous-hydrogen (GH2) streams. The model accounts for real-fluid thermodynamics and transport properties, making use of the Peng–Robinson equation of state and the Chung transport model. First, the development of a real-fluid model with an artificial neural network is described in detail. Then, the numerical results of the transcritical mixing layer (LOX/GH2) benchmark are presented and analyzed in terms of accuracy and computational efficiency. The results of the overall implementation indicate that the combined OpenFOAM and machine learning approach provides a speed-up factor higher than seven, while preserving the original solver accuracy.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

The H2-ICE project aims at developing, through numerical simulation, a new generation of hybrid powertrains featuring a hydrogen-fueled Internal Combustion Engine (ICE) suitable for 12 m urban buses in order to provide a reliable and cost-effective solution for the abatement of both CO2 and criteria pollutant emissions. The full exploitation of the potential of such a traction system requires a substantial enhancement of the state of the art since several issues have to be addressed. In particular, the choice of a more suitable fuel injection system and the control of the combustion process are extremely challenging. Firstly, a high-fidelity 3D-CFD model will be exploited to analyze the in-cylinder H2 fuel injection through supersonic flows. Then, after the optimization of the injection and combustion process, a 1D model of the whole engine system will be built and calibrated, allowing the identification of a “sweet spot” in the ultra-lean combustion region, characterized by extremely low NOx emissions and, at the same time, high combustion efficiencies. Moreover, to further enhance the engine efficiency well above 40%, different Waste Heat Recovery (WHR) systems will be carefully scrutinized, including both Organic Rankine Cycle (ORC)-based recovery units as well as electric turbo-compounding. A Selective Catalytic Reduction (SCR) aftertreatment system will be developed to further reduce NOx emissions to near-zero levels. Finally, a dedicated torque-based control strategy for the ICE coupled with the Energy Management Systems (EMSs) of the hybrid powertrain, both optimized by exploiting Vehicle-To-Everything (V2X) connection, allows targeting H2 consumption of 0.1 kg/km. Technologies developed in the H2-ICE project will enhance the know-how necessary to design and build engines and aftertreatment systems for the efficient exploitation of H2 as a fuel, as well as for their integration into hybrid powertrains.