Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in promising strategies to enhance or restore critical immune functions in allogeneic HSCT recipients. Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. This review summarizes and critically discusses the available data of immunotherapeutic strategies in allogeneic HSCT recipients suffering from invasive fungal infection

Illuminating nature's beauty: modular, scalable and low-cost LED dome illumination system using 3D-printing technology

Presenting your research in the proper light can be exceptionally challenging. Meanwhile, dome illumination systems became a standard for micro- and macrophotography in taxonomy, morphology, systematics and especially important in natural history collections. However, proper illumination systems are either expensive and/or laborious to use. Nowadays, 3D-printing technology revolutionizes lab-life and will soon find its way into most people's everyday life. Consequently, fused deposition modelling printers become more and more available, with online services offering personalized printing options. Here, we present a 3D-printed, scalable, low-cost and modular LED illumination dome system for scientific micro- and macrophotography. We provide stereolithography ('.stl') files and print settings, as well as a complete list of necessary components required for the construction of three differently sized domes. Additionally, we included an optional iris diaphragm and a sliding table, to arrange the object of desire inside the dome. The dome can be easily scaled and modified by adding customized parts, allowing you to always present your research object in the best light

Liposomal amphotericin B twice weekly as antifungal prophylaxis in paediatric haematological malignancy patients

AbstractData on antifungal prophylaxis in paediatric cancer patients at high risk for invasive fungal disease (IFD) are scant. Intermittent administration of liposomal amphotericin B (LAMB) has been shown to be safe and effective in adult patients with haematological malignancies. We prospectively evaluated the safety and efficacy of prophylactic LAMB at a dosage of 2.5 mg/kg twice weekly in children at high risk for IFD. Efficacy was compared with that in a historical control group of patients with similar demographic characteristics not receiving LAMB prophylaxis. A total of 46 high-risk patients (24 boys; mean age, 7.7 years) with 187 episodes of antifungal prophylaxis were analysed. The median duration of neutropenia (<500/µL) was 10 days. LAMB was discontinued in four patients because of acute allergic reactions. Median values for creatinine and liver enzymes at end of treatment did not differ significantly from those at baseline. Hypokalaemia (<3.0 mmol/L) occurred with 13.5% of the prophylactic episodes, but was usually mild and always reversible. No proven/probable IFD occurred in patients receiving LAMB prophylaxis. In comparison, five proven and two probable IFDs were observed in 45 historical controls not receiving LAMB prophylaxis (p 0.01). LAMB prophylaxis had no impact on the use of empirical antifungal therapy. Systemic antifungal prophylaxis with LAMB 2.5 mg/kg twice weekly is feasible and safe, and seems to be an effective approach for antifungal prophylaxis in high-risk paediatric cancer patients

Pathogen-reactive T helper cell analysis in the pig

There is growing interest in studying host-pathogen interactions in human-relevant large animal models such as the pig. Despite the progress in developing immunological reagents for porcine T cell research, there is an urgent need to directly assess pathogen-specific T cells-an extremely rare population of cells, but of upmost importance in orchestrating the host immune response to a given pathogen. Here, we established that the activation marker CD154 (CD40L), known from human and mouse studies, identifies also porcine antigen-reactive CD4(+) T lymphocytes. CD154 expression was upregulated early after antigen encounter and CD4(+)CD154(+) antigen-reactive T cells coexpressed cytokines. Antigen-induced expansion and autologous restimulation enabled a time-and dose-resolved analysis of CD154 regulation and a significantly increased resolution in phenotypic profiling of antigen-responsive cells. CD154 expression identified T cells responding to staphylococcal Enterotoxin B superantigen stimulation as well as T cells responding to the fungus Candida albicans and T cells specific for a highly prevalent intestinal parasite, the nematode Ascaris suum during acute and trickle infection. Antigen-reactive T cells were further detected after immunization of pigs with a single recombinant bacterial antigen of Streptococcus suis only. Thus, our study offers new ways to study antigen-specific T lymphocytes in the pig and their contribution to host-pathogen interactions

An experimental-numerical study of the adhesive static and dynamic friction of micro-patterned soft polymer surfaces

New possibilities have emerged in recent years, with the development of high-precision fabrication techniques, to exploit microscale surface patterning to modify tribological properties of polymeric materials. However, the effect of surface topography, together with material mechanical parameters, needs to be fully understood to allow the design of surfaces with the desired characteristics. In this paper, we experimentally assess the effect of various types of micropatterned Polydimethylsiloxane surfaces, including anisotropic ones, on macroscopic substrate friction properties. We find that it is possible, through surface patterning, to modify both static and dynamic friction coefficients of the surfaces, demonstrating the possibility of achieving tunability. Additionally, we compare experimental observations with the numerical predictions of a 2D Spring-Block model, deriving the material parameters from tests on the corresponding flat surfaces. We find a good quantitative agreement between calculated and measured trends for various micropattern geometries, demonstrating that the proposed numerical approach can reliably describe patterned surfaces when appropriate material parameters are used. The presented results can further contribute to the description and understanding of the frictional effects of surface patterning, with the aim of achieving surfaces with extreme tunability of tribological propertie

Fungal vaccines and immunotherapeutics: current concepts and future challenges

Purpose of review The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy. Recent findings Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches. Summary We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.ThisworkwassupportedbytheNorthernPortugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/ 2014 to A.C., and SFRH/BPD/96176/2013 to C.C).info:eu-repo/semantics/publishedVersio

The Granular Media Friction Pad: A Novel Biologically-Inspired System for Friction Maximization on a Wide Range of Substrates by Passive Jamming of Granular Material

Many solutions for getting grip on varying substrates exist in nature and in technical applications, but they fail on substrate geometries they are not specifically designed for. For maximizing friction forces on an unknown substrate, we developed a novel passive load-dependent system that creates high friction forces on a large variety of substrates: The granular media friction pad (GMFP), which consists of a thin elastic membrane encasing loosely filled granular material. When coming into contact with a substrate, the fluid-like granular material flows around the substrate asperities, and large contact areas with the substrate are achieved. Upon applying load, the granular material undergoes the jamming transition, rigidifies and becomes solid-like. High friction forces are generated by mechanical interlocking, internal friction of the granular media as well as by large contact area-mediated friction and deformation of the membrane. This system is able to adapt to a large variety of substrate topologies. First, we show the friction performance on different substrates and investigate the underlying physical mechanisms in a numerical simulation. We compare the granular media friction pad with bulk silicone samples both in stiffness under different loading conditions as well as for their friction performance on flat and rough substrates and a flat substrate contaminated by large particles. Then, we investigate the effect of elasticity variation on the generation of friction by varying granular media filling capacity as well as membrane modulus and thickness. The adaptability of the samples is tested by visualizing contact area with large substrate asperities present. Friction performance is evaluated on three different substrate types (flat, rough, contaminated). Finally, to further increase performance for moist or wet substrates, we adapt the granular media friction pad by structuring the outside of the membrane with a hexagon pattern. The friction performance of the structured and the smooth granular media friction pad is compared on a flat substrate when dry and when completely immersed in mineral oil. The hexagon structuring of the encasing membrane results in a significant increase in friction under lubricated conditions, thus greatly increasing the universal applicability of the granular media friction pad for a multitude of environments. Overall, the granular media friction pad is able to create high friction on unknown substrate geometries, which makes it suitable for a variety of use cases where stable grip on substrates is important.In der Natur und in technischen Anwendungen gibt es viele Lösungen, um festen Halt auf verschiedenen Untergründen zu erzeugen, doch diese versagen auf Untergrundgeometrien, für die sie nicht explizit konzipiert sind. Um Reibkräfte auf unbekannten Untergründen zu maximieren, haben wir ein neuartiges passives Anpressdruck-abhängiges System entwickelt, das auf einer großen Vielfalt von Untergründen hohe Reibkräfte erzeugt: Das Granular Media Friction Pad (Reibkissen mit granularer Materie), das aus einer dünnen elastischen Membran besteht, welche ein locker gefülltes granulares Material umhüllt. Wenn es mit einem Untergrund in Berührung kommt, legt sich das Flüssigkeit-artige granulare Material um die Rauhheiten des Untergrunds herum und erreicht hiermit große Kontaktflächen mit dem Untergrund. Sobald Anpressdruck aufgewandt wird, durchläuft das granulare Material die Jamming-Transition, verfestigt sich und wird Festkörper-artig. Hohe Reibkräfte werden erzeugt durch mechanisches Verhaken, interne Reibung des granularen Mediums sowie große Kontaktflächen-abhängige Reibung und Deformation der Membran. Dieses System ist dadurch in der Lage, sich an eine große Vielfalt von Untergrund-Topologien anzupassen. Zunächst zeigen wir die Reibleistung auf verschiedenen Untergründen und untersuchen die zugrundeliegenden physikalischen Mechanismen in einer numerischen Simulation. Wir vergleichen das Granular Media Friction Pad mit Vollsilikon-Proben bezüglich der Steifheit unter verschiedenen Anpressdrücken sowie ihrer Reibleistung auf flachen und rauhem Untergrund und einem flachen Untergrund, der durch große Partikel verunreinigt ist. Anschließend untersuchen wir die Auswirkungen von Änderungen in der Elastizität auf die Erzeugung von Reibung, indem wir die Füllkapazität des granularen Mediums sowie den Elastizitätsmodul und die Dicke der Membran variieren. Die Anpassungsfähigkeit der Proben wird untersucht, indem die Kontaktfläche in Anwesenheit von großen Substratrauhheiten visualisiert wird. Zudem wird die Reibleistung auf drei unterschiedlichen Untergrund-Typen (flach, rauh, verunreinigt) bewertet. Schließlich wird durch Strukturierung der Membran mit einem Hexagon-Profil die Leistung auf feuchten oder nassen Untergründen weiter erhöht. Dabei wird die Reibleistung von strukturiertem und glattem Granular Media Friction Pad auf einem flachen Untergrund in trockenem sowie in vollständig in Mineralöl eingetauchtem Zustand verglichen. Insgesamt ist das Granular Media Friction Pad in der Lage, hohe Reibkräfte auf unbekannten Untergrundgeometrien zu erzeugen, wodurch es für eine Vielfalt an Anwendungsfällen geeignet ist, bei denen ein fester Halt auf Untergründen wichtig ist

Bioinspired Granular Media Friction Pad: A Universal System for Friction Enhancement on Variety of Substrates

The granular media friction pad (GMFP) inspired by the biological smooth attachment pads of cockroaches and grasshoppers employs passive jamming, to create high friction forces on a large variety of substrates. The granular medium inside the pad is encased by a flexible membrane which at contact formation greatly adapts to the substrate profile. Upon applying load, the granular medium undergoes the jamming transition and changes from fluid-like to solid-like properties. The jammed granular medium, in combination with the deformation of the encasing elastic membrane, results in high friction forces on a multitude of substrate topographies. Here we explore the effect of elasticity variation on the generation of friction by varying granular media filling quantity as well as membrane modulus and thickness. We systematically investigate contact area and robustness against substrate contamination, and we also determine friction coefficients for various loading forces and substrates. Depending on the substrate topography and loading forces, a low filling quantity and a thin, elastic membrane can be favorable, in order to generate the highest friction forces